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Erschienen in: Journal of Diabetes & Metabolic Disorders 1/2021

21.04.2021 | Review article

Dysregulation of nitric oxide synthases during early and late pathophysiological conditions of diabetes mellitus leads to amassing of microvascular impedement

verfasst von: Varuna Suresh, Amala Reddy

Erschienen in: Journal of Diabetes & Metabolic Disorders | Ausgabe 1/2021

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Abstract

Diabetes is a major killer worldwide and its unprecedented rise poses a serious threat to mankind. According to recent estimation, 387 million people worldwide are affected from the disease with a prevalence rate of 8.3 and 46.3 % still remains undiagnosed. Important characteristics of diabetes are abnormalities of the physiological signalling functions of reactive oxygen species and reactive nitrogen species. Increased oxidative stress contributes to the activation of stress-sensitive intracellular signalling pathways and the development of gene products that trigger cellular damage and contribute to the vascular complications of diabetes. Growing evidence from studies into many diseases suggests that the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure are correlated with oxidative stress. This leads to cell metabolism and cell-cell homeostasis to be complexly dysregulated. This review focuses to investigate the status of oxidative stress, nitric oxide and reactive species in early and diabetes. Significance of nitric oxide synthases Evidences has accumulated indicating that the generation of reactive oxygen species (oxidative stress) may play an important role in the etiology of diabetic complications thus attention was given on the reactive oxygen and reactive nitrogen species and their potential role in pathogenesis. Additionally, the therapeutic advances in diabetes management are included. Nanotechnology, statins and stem cell technology are some techniques which can be considered to have a possible future in the treatment sector of diabetes.

Graphical abstract

Literatur
1.
Zurück zum Zitat Adela R, Nethi SK, Bagul PK, Barui AK, Mattapally S, Kuncha M, Patra CR, Reddy PN, Banerjee SK. Hyperglycaemia enhances nitric oxide production in diabetes: a study from South Indian patients. PloS one. 2015;10(4):e0125270.PubMedCrossRef Adela R, Nethi SK, Bagul PK, Barui AK, Mattapally S, Kuncha M, Patra CR, Reddy PN, Banerjee SK. Hyperglycaemia enhances nitric oxide production in diabetes: a study from South Indian patients. PloS one. 2015;10(4):e0125270.PubMedCrossRef
2.
Zurück zum Zitat Fowler MJ. Microvascular and macrovascular complications of diabetes. Clin Diabetes. 2008;26(2):77–82.CrossRef Fowler MJ. Microvascular and macrovascular complications of diabetes. Clin Diabetes. 2008;26(2):77–82.CrossRef
3.
Zurück zum Zitat Avogaro A, Albiero M, Menegazzo L, de Kreutzenberg S, Fadini GP. Endothelial dysfunction in diabetes: the role of reparatory mechanisms. Diabetes Care. 2011;34(Supplement 2):285-90. Avogaro A, Albiero M, Menegazzo L, de Kreutzenberg S, Fadini GP. Endothelial dysfunction in diabetes: the role of reparatory mechanisms. Diabetes Care. 2011;34(Supplement 2):285-90.
5.
Zurück zum Zitat Pieper GM. Review of alterations in endothelial nitric oxide production in diabetes: protective role of arginine on endothelial dysfunction. Hypertension. 1998;31(5):1047–60.PubMedCrossRef Pieper GM. Review of alterations in endothelial nitric oxide production in diabetes: protective role of arginine on endothelial dysfunction. Hypertension. 1998;31(5):1047–60.PubMedCrossRef
6.
Zurück zum Zitat Hall AV, Antoniou H, Wang Y, Cheung AH, Arbus AM, Olson SL, Lu WC, Kau CL, Marsden PA. Structural organization of the human neuronal nitric oxide synthase gene (NOS1). J Biol Chem. 1994;269(52):33082–90.PubMedCrossRef Hall AV, Antoniou H, Wang Y, Cheung AH, Arbus AM, Olson SL, Lu WC, Kau CL, Marsden PA. Structural organization of the human neuronal nitric oxide synthase gene (NOS1). J Biol Chem. 1994;269(52):33082–90.PubMedCrossRef
7.
Zurück zum Zitat Boissel JP, Schwarz PM, Förstermann U. Neuronal-type NO synthase: transcript diversity and expressional regulation. Nitric Oxide. 1998;2(5):337–49.PubMedCrossRef Boissel JP, Schwarz PM, Förstermann U. Neuronal-type NO synthase: transcript diversity and expressional regulation. Nitric Oxide. 1998;2(5):337–49.PubMedCrossRef
8.
Zurück zum Zitat Mungrue IN, Husain M, Stewart DJ. The role of NOS in heart failure: lessons from murine genetic models. In: The role of nitric oxide in heart failure. Boston: Springer; 2004. pp. 113–128. Mungrue IN, Husain M, Stewart DJ. The role of NOS in heart failure: lessons from murine genetic models. In: The role of nitric oxide in heart failure. Boston: Springer; 2004. pp. 113–128.
9.
Zurück zum Zitat Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33(7):829–37.PubMedCrossRef Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33(7):829–37.PubMedCrossRef
10.
Zurück zum Zitat Weis U, Turner B, Gibney J, Watts GF, Burke V, Shaw KM, Cummings MH. Long-term predictors of coronary artery disease and mortality in type 1 diabetes. Qjm. 2001;94(11):623–30.PubMedCrossRef Weis U, Turner B, Gibney J, Watts GF, Burke V, Shaw KM, Cummings MH. Long-term predictors of coronary artery disease and mortality in type 1 diabetes. Qjm. 2001;94(11):623–30.PubMedCrossRef
11.
Zurück zum Zitat van de Ree MA, Huisman MV, de Man FH, van der Vijver JC, Meinders AE, Blauw GJ. Impaired endothelium-dependent vasodilation in type 2 diabetes mellitus and the lack of effect of simvastatin. Cardiovasc Res. 2001;52(2):299–305.PubMedCrossRef van de Ree MA, Huisman MV, de Man FH, van der Vijver JC, Meinders AE, Blauw GJ. Impaired endothelium-dependent vasodilation in type 2 diabetes mellitus and the lack of effect of simvastatin. Cardiovasc Res. 2001;52(2):299–305.PubMedCrossRef
12.
Zurück zum Zitat Shukla SD, Paul A, Klachko DM. Hypersensitivity of diabetic human platelets to platelet activating factor. Thromb Res. 1992;66(2–3):239–46.PubMedCrossRef Shukla SD, Paul A, Klachko DM. Hypersensitivity of diabetic human platelets to platelet activating factor. Thromb Res. 1992;66(2–3):239–46.PubMedCrossRef
13.
Zurück zum Zitat Zhou L, Zhu DY. Neuronal nitric oxide synthase: structure, subcellular localization, regulation, and clinical implications. Nitric Oxide. 2009;20(4):223–30.PubMedCrossRef Zhou L, Zhu DY. Neuronal nitric oxide synthase: structure, subcellular localization, regulation, and clinical implications. Nitric Oxide. 2009;20(4):223–30.PubMedCrossRef
14.
Zurück zum Zitat Förstermann U, Closs EI, Pollock JS, Nakane M, Schwarz P, Gath I, Kleinert H. Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. Hypertension. 1994;23(6_pt_2):1121–31.PubMedCrossRef Förstermann U, Closs EI, Pollock JS, Nakane M, Schwarz P, Gath I, Kleinert H. Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. Hypertension. 1994;23(6_pt_2):1121–31.PubMedCrossRef
15.
Zurück zum Zitat Nakane M, Schmidt HH, Pollock JS, Förstermann U, Murad F. Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEBS Lett. 1993;316(2):175–80.PubMedCrossRef Nakane M, Schmidt HH, Pollock JS, Förstermann U, Murad F. Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEBS Lett. 1993;316(2):175–80.PubMedCrossRef
16.
Zurück zum Zitat Kone BC, Kuncewicz T, Zhang W, Yu ZY. Protein interactions with nitric oxide synthases: controlling the right time, the right place, and the right amount of nitric oxide. Am J Physiol Renal Physiol. 2003;285(2):F178-90.PubMedCrossRef Kone BC, Kuncewicz T, Zhang W, Yu ZY. Protein interactions with nitric oxide synthases: controlling the right time, the right place, and the right amount of nitric oxide. Am J Physiol Renal Physiol. 2003;285(2):F178-90.PubMedCrossRef
17.
Zurück zum Zitat Sharma JN, Al-Omran A, Parvathy SS. Role of nitric oxide in inflammatory diseases. Inflammopharmacology. 2007;15(6):252–9.PubMedCrossRef Sharma JN, Al-Omran A, Parvathy SS. Role of nitric oxide in inflammatory diseases. Inflammopharmacology. 2007;15(6):252–9.PubMedCrossRef
18.
Zurück zum Zitat MacMicking J, Xie QW, Nathan C. Nitric oxide and macrophage function. Annu Rev Immunol. 1997;15(1):323–50.PubMedCrossRef MacMicking J, Xie QW, Nathan C. Nitric oxide and macrophage function. Annu Rev Immunol. 1997;15(1):323–50.PubMedCrossRef
19.
Zurück zum Zitat Marsden PA, Schappert KT, Chen HS, Flowers M, Sundell CL, Wilcox JN, Lamas S, Michel T. Molecular cloning and characterization of human endothelial nitric oxide synthase. FEBS Lett. 1992;307(3):287–93.PubMedCrossRef Marsden PA, Schappert KT, Chen HS, Flowers M, Sundell CL, Wilcox JN, Lamas S, Michel T. Molecular cloning and characterization of human endothelial nitric oxide synthase. FEBS Lett. 1992;307(3):287–93.PubMedCrossRef
20.
Zurück zum Zitat Fish JE, Marsden PA. Endothelial nitric oxide synthase: insight into cell-specific gene regulation in the vascular endothelium. Cell Mol Life Sci. 2006;63(2):144–62.PubMedCrossRef Fish JE, Marsden PA. Endothelial nitric oxide synthase: insight into cell-specific gene regulation in the vascular endothelium. Cell Mol Life Sci. 2006;63(2):144–62.PubMedCrossRef
21.
Zurück zum Zitat Cortese-Krott MM, Rodriguez-Mateos A, Sansone R, Kuhnle GG, Thasian-Sivarajah S, Krenz T, Horn P, Krisp C, Wolters D, Heiß C, Kröncke KD. Human red blood cells at work: identification and visualization of erythrocytic eNOS activity in health and disease. Blood. 2012;120(20):4229–37.PubMedCrossRef Cortese-Krott MM, Rodriguez-Mateos A, Sansone R, Kuhnle GG, Thasian-Sivarajah S, Krenz T, Horn P, Krisp C, Wolters D, Heiß C, Kröncke KD. Human red blood cells at work: identification and visualization of erythrocytic eNOS activity in health and disease. Blood. 2012;120(20):4229–37.PubMedCrossRef
22.
Zurück zum Zitat Smith BC, Underbakke ES, Kulp DW, Schief WR, Marletta MA. Nitric oxide synthase domain interfaces regulate electron transfer and calmodulin activation. Proc Natl Acad Sci. 2013;110(38):E3577-86.PubMedCrossRef Smith BC, Underbakke ES, Kulp DW, Schief WR, Marletta MA. Nitric oxide synthase domain interfaces regulate electron transfer and calmodulin activation. Proc Natl Acad Sci. 2013;110(38):E3577-86.PubMedCrossRef
23.
Zurück zum Zitat Crane BR, Arvai AS, Ghosh DK, Wu C, Getzoff ED, Stuehr DJ, Tainer JA. Structure of nitric oxide synthase oxygenase dimer with pterin and substrate. Science. 1998;279(5359):2121–6.PubMedCrossRef Crane BR, Arvai AS, Ghosh DK, Wu C, Getzoff ED, Stuehr DJ, Tainer JA. Structure of nitric oxide synthase oxygenase dimer with pterin and substrate. Science. 1998;279(5359):2121–6.PubMedCrossRef
24.
Zurück zum Zitat Nishimura JS, Martasek P, McMillan K, Salerno JC, Liu Q, Gross SS, Masters BS. Modular structure of neuronal nitric oxide synthase: localization of the arginine binding site and modulation by pterin. Biochem Biophys Res Commun. 1995;210(2):288–94.PubMedCrossRef Nishimura JS, Martasek P, McMillan K, Salerno JC, Liu Q, Gross SS, Masters BS. Modular structure of neuronal nitric oxide synthase: localization of the arginine binding site and modulation by pterin. Biochem Biophys Res Commun. 1995;210(2):288–94.PubMedCrossRef
25.
Zurück zum Zitat Stuehr D, Pou S, Rosen GM. Oxygen reduction by nitric-oxide synthases. J Biol Chem. 2001;276(18):14533–6.PubMedCrossRef Stuehr D, Pou S, Rosen GM. Oxygen reduction by nitric-oxide synthases. J Biol Chem. 2001;276(18):14533–6.PubMedCrossRef
26.
Zurück zum Zitat Cho HJ, Xie QW, Calaycay J, Mumford RA, Swiderek KM, Lee TD, Nathan C. Calmodulin is a subunit of nitric oxide synthase from macrophages. J Exp Med. 1992;176(2):599–604.PubMedCrossRef Cho HJ, Xie QW, Calaycay J, Mumford RA, Swiderek KM, Lee TD, Nathan C. Calmodulin is a subunit of nitric oxide synthase from macrophages. J Exp Med. 1992;176(2):599–604.PubMedCrossRef
27.
Zurück zum Zitat Hemmens B, Mayer B. Enzymology of nitric oxide synthases. InNitric oxide protocols. Totowa: Humana Press. 1998. pp. 1–32. Hemmens B, Mayer B. Enzymology of nitric oxide synthases. InNitric oxide protocols. Totowa: Humana Press. 1998. pp. 1–32.
28.
Zurück zum Zitat Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci. 1991;14(2):60–7.PubMedCrossRef Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci. 1991;14(2):60–7.PubMedCrossRef
29.
Zurück zum Zitat Peach MJ, Loeb AL, Singer HA, Saye JO. Endothelium-derived vascular relaxing factor. Hypertension. 1985;7(3_pt_2):I94.PubMedCrossRef Peach MJ, Loeb AL, Singer HA, Saye JO. Endothelium-derived vascular relaxing factor. Hypertension. 1985;7(3_pt_2):I94.PubMedCrossRef
30.
Zurück zum Zitat García-Cardeña G, Fan R, Shah V, Sorrentino R, Cirino G, Papapetropoulos A, Sessa WC. Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature. 1998;392(6678):821–4.PubMedCrossRef García-Cardeña G, Fan R, Shah V, Sorrentino R, Cirino G, Papapetropoulos A, Sessa WC. Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature. 1998;392(6678):821–4.PubMedCrossRef
31.
Zurück zum Zitat Stokoe D, Stephens LR, Copeland T, Gaffney PR, Reese CB, Painter GF, Holmes AB, McCormick F, Hawkins PT. Dual role of phosphatidylinositol-3, 4, 5-trisphosphate in the activation of protein kinase B. Science. 1997;277(5325):567–70.PubMedCrossRef Stokoe D, Stephens LR, Copeland T, Gaffney PR, Reese CB, Painter GF, Holmes AB, McCormick F, Hawkins PT. Dual role of phosphatidylinositol-3, 4, 5-trisphosphate in the activation of protein kinase B. Science. 1997;277(5325):567–70.PubMedCrossRef
32.
Zurück zum Zitat Kobayashi T, Taguchi K, Yasuhiro T, Matsumoto T, Kamata K. Impairment of PI3-K/Akt pathway underlies attenuated endothelial function in aorta of type 2 diabetic mouse model. Hypertension. 2004;44(6):956–62.CrossRef Kobayashi T, Taguchi K, Yasuhiro T, Matsumoto T, Kamata K. Impairment of PI3-K/Akt pathway underlies attenuated endothelial function in aorta of type 2 diabetic mouse model. Hypertension. 2004;44(6):956–62.CrossRef
33.
Zurück zum Zitat Ji H, Pesce C, Zheng W, Kim J, Zhang Y, Menini S, Haywood JR, Sandberg K. Sex differences in renal injury and nitric oxide production in renal wrap hypertension. Am J Physiol Heart Circ Physiol. 2005;288(1):H43-7.PubMedCrossRef Ji H, Pesce C, Zheng W, Kim J, Zhang Y, Menini S, Haywood JR, Sandberg K. Sex differences in renal injury and nitric oxide production in renal wrap hypertension. Am J Physiol Heart Circ Physiol. 2005;288(1):H43-7.PubMedCrossRef
34.
Zurück zum Zitat Forte P, Kneale BJ, Milne E, Chowienczyk PJ, Johnston A, Benjamin N, Ritter JM. Evidence for a difference in nitric oxide biosynthesis between healthy women and men. Hypertension. 1998;32(4):730–4.PubMedCrossRef Forte P, Kneale BJ, Milne E, Chowienczyk PJ, Johnston A, Benjamin N, Ritter JM. Evidence for a difference in nitric oxide biosynthesis between healthy women and men. Hypertension. 1998;32(4):730–4.PubMedCrossRef
35.
Zurück zum Zitat Sader MA, Celermajer DS. Endothelial function, vascular reactivity and gender differences in the cardiovascular system. Cardiovasc Res. 2002;53(3):597–604.PubMedCrossRef Sader MA, Celermajer DS. Endothelial function, vascular reactivity and gender differences in the cardiovascular system. Cardiovasc Res. 2002;53(3):597–604.PubMedCrossRef
36.
Zurück zum Zitat Taguchi K, Matsumoto T, Kamata K, Kobayashi T. Akt/eNOS pathway activation in endothelium-dependent relaxation is preserved in aortas from female, but not from male, type 2 diabetic mice. Pharmacol Res. 2012;65(1):56–65.PubMedCrossRef Taguchi K, Matsumoto T, Kamata K, Kobayashi T. Akt/eNOS pathway activation in endothelium-dependent relaxation is preserved in aortas from female, but not from male, type 2 diabetic mice. Pharmacol Res. 2012;65(1):56–65.PubMedCrossRef
37.
Zurück zum Zitat D’Autréaux B, Toledano MB. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol. 2007;8(10):813–24.PubMedCrossRef D’Autréaux B, Toledano MB. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol. 2007;8(10):813–24.PubMedCrossRef
38.
Zurück zum Zitat Steinert JR, Chernova T, Forsythe ID. Nitric oxide signaling in brain function, dysfunction, and dementia. Neuroscientist. 2010;16(4):435–52.PubMedCrossRef Steinert JR, Chernova T, Forsythe ID. Nitric oxide signaling in brain function, dysfunction, and dementia. Neuroscientist. 2010;16(4):435–52.PubMedCrossRef
39.
Zurück zum Zitat Lipton SA, Choi YB, Pan ZH, Lei SZ, Chen HS, Sucher NJ, Loscalzo J, Singel DJ, Stamler JS. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature. 1993;364(6438):626–32.PubMedCrossRef Lipton SA, Choi YB, Pan ZH, Lei SZ, Chen HS, Sucher NJ, Loscalzo J, Singel DJ, Stamler JS. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature. 1993;364(6438):626–32.PubMedCrossRef
40.
Zurück zum Zitat Tottrup A, Svane D, Forman A. Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter. Am J Physiol Gastrointest Liver Physiol. 1991;260(3):G385-9.CrossRef Tottrup A, Svane D, Forman A. Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter. Am J Physiol Gastrointest Liver Physiol. 1991;260(3):G385-9.CrossRef
41.
Zurück zum Zitat Vareniuk I, Pacher P, Pavlov IA, Drel VR, Obrosova IG. Peripheral neuropathy in mice with neuronal nitric oxide synthase gene deficiency. Int J Mol Med. 2009;23(5):571–80.PubMedPubMedCentral Vareniuk I, Pacher P, Pavlov IA, Drel VR, Obrosova IG. Peripheral neuropathy in mice with neuronal nitric oxide synthase gene deficiency. Int J Mol Med. 2009;23(5):571–80.PubMedPubMedCentral
42.
Zurück zum Zitat Cellek S. Point of NO return for nitrergic nerves in diabetes: a new insight into diabetic complications. Curr Pharm Des. 2004;10(29):3683–95.PubMedCrossRef Cellek S. Point of NO return for nitrergic nerves in diabetes: a new insight into diabetic complications. Curr Pharm Des. 2004;10(29):3683–95.PubMedCrossRef
43.
Zurück zum Zitat Fehsel K, Jalowy A, Qi S, Burkart V, Hartmann B, Kolb H. Islet cell DNA is a target of inflammatory attack by nitric oxide. Diabetes. 1993;42(3):496–500.PubMedCrossRef Fehsel K, Jalowy A, Qi S, Burkart V, Hartmann B, Kolb H. Islet cell DNA is a target of inflammatory attack by nitric oxide. Diabetes. 1993;42(3):496–500.PubMedCrossRef
44.
Zurück zum Zitat Kröncke KD, Kolb-Bachofen V, Berschick B, Burkart V, Kolb H. Activated macrophages kill pancreatic syngeneic islet cells via arginine-dependent nitric oxide generation. Biochem Biophys Res Commun. 1991;175(3):752–8.PubMedCrossRef Kröncke KD, Kolb-Bachofen V, Berschick B, Burkart V, Kolb H. Activated macrophages kill pancreatic syngeneic islet cells via arginine-dependent nitric oxide generation. Biochem Biophys Res Commun. 1991;175(3):752–8.PubMedCrossRef
45.
Zurück zum Zitat Langrehr JM, Hoffman RA, Billiar TR, Lee KK, Schraut WH, Simmons RL. Nitric oxide synthesis in the in vivo allograft response: a possible regulatory mechanism. Surgery. 1991;110(2):335.PubMed Langrehr JM, Hoffman RA, Billiar TR, Lee KK, Schraut WH, Simmons RL. Nitric oxide synthesis in the in vivo allograft response: a possible regulatory mechanism. Surgery. 1991;110(2):335.PubMed
46.
Zurück zum Zitat Kanwar JR, Kanwar RK, Burrow H, Baratchi S. Recent advances on the roles of NO in cancer and chronic inflammatory disorders. Curr Med Chem. 2009;16(19):2373–94.PubMedCrossRef Kanwar JR, Kanwar RK, Burrow H, Baratchi S. Recent advances on the roles of NO in cancer and chronic inflammatory disorders. Curr Med Chem. 2009;16(19):2373–94.PubMedCrossRef
47.
Zurück zum Zitat Brown GC, Neher JJ. Inflammatory neurodegeneration and mechanisms of microglial killing of neurons. Mol Neurobiol. 2010;41(2–3):242–7.PubMedCrossRef Brown GC, Neher JJ. Inflammatory neurodegeneration and mechanisms of microglial killing of neurons. Mol Neurobiol. 2010;41(2–3):242–7.PubMedCrossRef
48.
Zurück zum Zitat Viaro F, Nobre F, Paulo Roberto B, Evora. Expression of nitric oxide synthases in the pathophysiology of cardiovascular diseases. Arq Bras Cardiol. 2000;74(4):380–93.PubMedCrossRef Viaro F, Nobre F, Paulo Roberto B, Evora. Expression of nitric oxide synthases in the pathophysiology of cardiovascular diseases. Arq Bras Cardiol. 2000;74(4):380–93.PubMedCrossRef
49.
Zurück zum Zitat MacMicking JD, Nathan C, Hom G, Chartrain N, Fletcher DS, Trumbauer M, Stevens K, Xie QW, Sokol K, Hutchinson N, Chen H. Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell. 1995;81(4):641–50.PubMedCrossRef MacMicking JD, Nathan C, Hom G, Chartrain N, Fletcher DS, Trumbauer M, Stevens K, Xie QW, Sokol K, Hutchinson N, Chen H. Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell. 1995;81(4):641–50.PubMedCrossRef
50.
Zurück zum Zitat Lange M, Enkhbaatar P, Nakano Y, Traber DL. Role of nitric oxide in shock: the large animal perspective. Front Biosci. 2009;14(1):1979–89.CrossRef Lange M, Enkhbaatar P, Nakano Y, Traber DL. Role of nitric oxide in shock: the large animal perspective. Front Biosci. 2009;14(1):1979–89.CrossRef
52.
Zurück zum Zitat Molnár A, Tóth A, Bagi Z, Papp Z, Édes I, Vaszily M, Galajda Z, Papp JG, Varró A, Szüts V, Lacza Z. Activation of the poly (ADP-ribose) polymerase pathway in human heart failure. Mol Med. 2006;12(7):143–52.PubMedCrossRef Molnár A, Tóth A, Bagi Z, Papp Z, Édes I, Vaszily M, Galajda Z, Papp JG, Varró A, Szüts V, Lacza Z. Activation of the poly (ADP-ribose) polymerase pathway in human heart failure. Mol Med. 2006;12(7):143–52.PubMedCrossRef
53.
Zurück zum Zitat Virág L, Szabó C. The therapeutic potential of poly (ADP-ribose) polymerase inhibitors. Pharmacol Rev. 2002;54(3):375–429.PubMedCrossRef Virág L, Szabó C. The therapeutic potential of poly (ADP-ribose) polymerase inhibitors. Pharmacol Rev. 2002;54(3):375–429.PubMedCrossRef
54.
Zurück zum Zitat Du XL, Edelstein D, Dimmeler S, Ju Q, Sui C, Brownlee M. Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. J Clin Investig. 2001;108(9):1341–8.PubMedCrossRef Du XL, Edelstein D, Dimmeler S, Ju Q, Sui C, Brownlee M. Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. J Clin Investig. 2001;108(9):1341–8.PubMedCrossRef
55.
Zurück zum Zitat Dellamea BS, Leitão CB, Friedman R, Canani LH. Nitric oxide system and diabetic nephropathy. Diabetol Metab Syndr. 2014;6(1):17.PubMedCrossRef Dellamea BS, Leitão CB, Friedman R, Canani LH. Nitric oxide system and diabetic nephropathy. Diabetol Metab Syndr. 2014;6(1):17.PubMedCrossRef
56.
Zurück zum Zitat Caimi G, Hopps E, Montana M, Noto D, Canino B, Presti RL, Averna MR. Evaluation of nitric oxide metabolites in a group of subjects with metabolic syndrome. Diabetes Metab Syndr Clin Res Rev. 2012;6(3):132–5.CrossRef Caimi G, Hopps E, Montana M, Noto D, Canino B, Presti RL, Averna MR. Evaluation of nitric oxide metabolites in a group of subjects with metabolic syndrome. Diabetes Metab Syndr Clin Res Rev. 2012;6(3):132–5.CrossRef
57.
Zurück zum Zitat Zou MH, Cohen RA, Ullrich V. Peroxynitrite and vascular endothelial dysfunction in diabetes mellitus. Endothelium. 2004;11(2):89–97. Zou MH, Cohen RA, Ullrich V. Peroxynitrite and vascular endothelial dysfunction in diabetes mellitus. Endothelium. 2004;11(2):89–97.
58.
Zurück zum Zitat Ishii N, Patel KP, Lane PH, Taylor T, Bian KA, Murad F, Pollock JS, Carmines PK. Nitric oxide synthesis and oxidative stress in the renal cortex of rats with diabetes mellitus. J Am Soc Nephrol. 2001;12(8):1630–9.PubMedCrossRef Ishii N, Patel KP, Lane PH, Taylor T, Bian KA, Murad F, Pollock JS, Carmines PK. Nitric oxide synthesis and oxidative stress in the renal cortex of rats with diabetes mellitus. J Am Soc Nephrol. 2001;12(8):1630–9.PubMedCrossRef
59.
Zurück zum Zitat Cosentino F, Hishikawa K, Katusic ZS, Lüscher TF. High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation. 1997;96(1):25–8.PubMedCrossRef Cosentino F, Hishikawa K, Katusic ZS, Lüscher TF. High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation. 1997;96(1):25–8.PubMedCrossRef
60.
Zurück zum Zitat Hoeldtke RD, Bryner KD, McNeill DR, Warehime SS, Van Dyke K, Hobbs G. Oxidative stress and insulin requirements in patients with recent-onset type 1 diabetes. J Clin Endocrinol Metab. 2003;88(4):1624–8.PubMedCrossRef Hoeldtke RD, Bryner KD, McNeill DR, Warehime SS, Van Dyke K, Hobbs G. Oxidative stress and insulin requirements in patients with recent-onset type 1 diabetes. J Clin Endocrinol Metab. 2003;88(4):1624–8.PubMedCrossRef
61.
Zurück zum Zitat Eizirik DL, Flodström M, Karlsen AE, Welsh N. The harmony of the spheres: inducible nitric oxide synthase and related genes in pancreatic beta cells. Diabetologia. 1996;39(8):875–90.PubMedCrossRef Eizirik DL, Flodström M, Karlsen AE, Welsh N. The harmony of the spheres: inducible nitric oxide synthase and related genes in pancreatic beta cells. Diabetologia. 1996;39(8):875–90.PubMedCrossRef
62.
Zurück zum Zitat Kaneko YK, Ishikawa T. Dual role of nitric oxide in pancreatic β-cells. J Pharmacol Sci. 2013;123(4):295–300.CrossRef Kaneko YK, Ishikawa T. Dual role of nitric oxide in pancreatic β-cells. J Pharmacol Sci. 2013;123(4):295–300.CrossRef
63.
Zurück zum Zitat Cantu-Medellin N, Kelley EE. Xanthine oxidoreductase-catalyzed reduction of nitrite to nitric oxide: insights regarding where, when and how. Nitric Oxide. 2013;34:19–26.PubMedPubMedCentralCrossRef Cantu-Medellin N, Kelley EE. Xanthine oxidoreductase-catalyzed reduction of nitrite to nitric oxide: insights regarding where, when and how. Nitric Oxide. 2013;34:19–26.PubMedPubMedCentralCrossRef
64.
Zurück zum Zitat Battelli MG, Polito L, Bolognesi A. Xanthine oxidoreductase in atherosclerosis pathogenesis: not only oxidative stress. Atherosclerosis. 2014;237(2):562–7.PubMedCrossRef Battelli MG, Polito L, Bolognesi A. Xanthine oxidoreductase in atherosclerosis pathogenesis: not only oxidative stress. Atherosclerosis. 2014;237(2):562–7.PubMedCrossRef
65.
Zurück zum Zitat Higashi Y, Oshima T, Sasaki N, Ishioka N, Nakano Y, Ozono R, Yoshimura M, Ishibashi K, Matsuura H, Kajiyama G. Relationship between insulin resistance and endothelium-dependent vascular relaxation in patients with essential hypertension. Hypertension. 1997;29(1):280–5.PubMedCrossRef Higashi Y, Oshima T, Sasaki N, Ishioka N, Nakano Y, Ozono R, Yoshimura M, Ishibashi K, Matsuura H, Kajiyama G. Relationship between insulin resistance and endothelium-dependent vascular relaxation in patients with essential hypertension. Hypertension. 1997;29(1):280–5.PubMedCrossRef
66.
Zurück zum Zitat Windebank A, Feldman E. Diabetes and the nervous system. In: Aminoff M, editor. Neurology and general medicine. Philadelphia: Churchill Livingstone. 2001. p. 341–364. Windebank A, Feldman E. Diabetes and the nervous system. In: Aminoff M, editor. Neurology and general medicine. Philadelphia: Churchill Livingstone. 2001. p. 341–364.
67.
Zurück zum Zitat Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia. 2001;44(2):129–46.PubMedCrossRef Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia. 2001;44(2):129–46.PubMedCrossRef
68.
Zurück zum Zitat Cameron NE, Eaton SE, Cotter MA, Tesfaye S. Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia. 2001;44(11):1973–88.PubMedCrossRef Cameron NE, Eaton SE, Cotter MA, Tesfaye S. Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia. 2001;44(11):1973–88.PubMedCrossRef
69.
Zurück zum Zitat Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T. Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science. 1995;270(5234):296–9.PubMedCrossRef Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T. Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science. 1995;270(5234):296–9.PubMedCrossRef
70.
Zurück zum Zitat Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87(1):245–313.PubMedCrossRef Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87(1):245–313.PubMedCrossRef
71.
Zurück zum Zitat Zhang DX, Gutterman DD. Mitochondrial reactive oxygen species-mediated signaling in endothelial cells. Am J Physiol Heart Circ Physiol. 2007;292(5):H2023-31.PubMedCrossRef Zhang DX, Gutterman DD. Mitochondrial reactive oxygen species-mediated signaling in endothelial cells. Am J Physiol Heart Circ Physiol. 2007;292(5):H2023-31.PubMedCrossRef
72.
Zurück zum Zitat Kanda M, Ihara Y, Murata H, Urata Y, Kono T, Yodoi J, Seto S, Yano K, Kondo T. Glutaredoxin modulates platelet-derived growth factor-dependent cell signaling by regulating the redox status of low molecular weight protein-tyrosine phosphatase. J Biol Chem. 2006;281(39):28518–28.PubMedCrossRef Kanda M, Ihara Y, Murata H, Urata Y, Kono T, Yodoi J, Seto S, Yano K, Kondo T. Glutaredoxin modulates platelet-derived growth factor-dependent cell signaling by regulating the redox status of low molecular weight protein-tyrosine phosphatase. J Biol Chem. 2006;281(39):28518–28.PubMedCrossRef
73.
Zurück zum Zitat Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev. 2002;23(5):599–622.PubMedCrossRef Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev. 2002;23(5):599–622.PubMedCrossRef
74.
Zurück zum Zitat Piconi L, Quagliaro L, Da Ros R, Assaloni R, Giugliano D, Esposito K, Szabo C, Ceriello A. Intermittent high glucose enhances ICAM-1, VCAM‐1, E‐selectin and interleukin‐6 expression in human umbilical endothelial cells in culture: the role of poly (ADP‐ribose) polymerase. J Thromb Haemost. 2004;2(8):1453–9.PubMedCrossRef Piconi L, Quagliaro L, Da Ros R, Assaloni R, Giugliano D, Esposito K, Szabo C, Ceriello A. Intermittent high glucose enhances ICAM-1, VCAM‐1, E‐selectin and interleukin‐6 expression in human umbilical endothelial cells in culture: the role of poly (ADP‐ribose) polymerase. J Thromb Haemost. 2004;2(8):1453–9.PubMedCrossRef
75.
Zurück zum Zitat Cagliero E, Maiello M, Boeri D, Roy S, Lorenzi M. Increased expression of basement membrane components in human endothelial cells cultured in high glucose. J Clin Investig. 1988;82(2):735–8.PubMedCrossRef Cagliero E, Maiello M, Boeri D, Roy S, Lorenzi M. Increased expression of basement membrane components in human endothelial cells cultured in high glucose. J Clin Investig. 1988;82(2):735–8.PubMedCrossRef
76.
Zurück zum Zitat Poitout V, Robertson RP. Glucolipotoxicity: fuel excess and β-cell dysfunction. Endocr Rev. 2008;29(3):351–66.PubMedCrossRef Poitout V, Robertson RP. Glucolipotoxicity: fuel excess and β-cell dysfunction. Endocr Rev. 2008;29(3):351–66.PubMedCrossRef
77.
Zurück zum Zitat El-Assaad W, Buteau J, Peyot ML, Nolan C, Roduit R, Hardy S, Joly E, Dbaibo G, Rosenberg L, Prentki M. Saturated fatty acids synergize with elevated glucose to cause pancreatic β-cell death. Endocrinology. 2003;144(9):4154–63.PubMedCrossRef El-Assaad W, Buteau J, Peyot ML, Nolan C, Roduit R, Hardy S, Joly E, Dbaibo G, Rosenberg L, Prentki M. Saturated fatty acids synergize with elevated glucose to cause pancreatic β-cell death. Endocrinology. 2003;144(9):4154–63.PubMedCrossRef
78.
Zurück zum Zitat Harmon JS, Gleason CE, Tanaka Y, Poitout V, Robertson RP. Antecedent hyperglycemia, not hyperlipidemia, is associated with increased islet triacylglycerol content and decreased insulin gene mRNA level in Zucker diabetic fatty rats. Diabetes. 2001;50(11):2481–6.PubMedCrossRef Harmon JS, Gleason CE, Tanaka Y, Poitout V, Robertson RP. Antecedent hyperglycemia, not hyperlipidemia, is associated with increased islet triacylglycerol content and decreased insulin gene mRNA level in Zucker diabetic fatty rats. Diabetes. 2001;50(11):2481–6.PubMedCrossRef
79.
Zurück zum Zitat Kaneto H, Fujii J, Myint T, Miyazawa N, Islam KN, Kawasaki Y, Suzuki K, Nakamura M, Tatsumi H, Yamasaki Y, Taniguchi N. Reducing sugars trigger oxidative modification and apoptosis in pancreatic β-cells by provoking oxidative stress through the glycation reaction. Biochem J. 1996;320(3):855–63.PubMedPubMedCentralCrossRef Kaneto H, Fujii J, Myint T, Miyazawa N, Islam KN, Kawasaki Y, Suzuki K, Nakamura M, Tatsumi H, Yamasaki Y, Taniguchi N. Reducing sugars trigger oxidative modification and apoptosis in pancreatic β-cells by provoking oxidative stress through the glycation reaction. Biochem J. 1996;320(3):855–63.PubMedPubMedCentralCrossRef
80.
Zurück zum Zitat Tajiri Y, Möller C, Grill V. Long term effects of aminoguanidine on insulin release and biosynthesis: evidence that the formation of advanced glycosylation end products inhibits B cell function. Endocrinology. 1997;138(1):273–80.PubMedCrossRef Tajiri Y, Möller C, Grill V. Long term effects of aminoguanidine on insulin release and biosynthesis: evidence that the formation of advanced glycosylation end products inhibits B cell function. Endocrinology. 1997;138(1):273–80.PubMedCrossRef
81.
Zurück zum Zitat Kaneto H, Nakatani Y, Kawamori D, Miyatsuka T, Matsuoka TA. Involvement of oxidative stress and the JNK pathway in glucose toxicity. Rev Diabet Stud. 2004;1(4):165.PubMedCrossRef Kaneto H, Nakatani Y, Kawamori D, Miyatsuka T, Matsuoka TA. Involvement of oxidative stress and the JNK pathway in glucose toxicity. Rev Diabet Stud. 2004;1(4):165.PubMedCrossRef
82.
Zurück zum Zitat Robbins CS, Chudnovskiy A, Rauch PJ, Figueiredo JL, Iwamoto Y, Gorbatov R, Etzrodt M, Weber GF, Ueno T, van Rooijen N, Mulligan-Kehoe MJ. Extramedullary hematopoiesis generates Ly-6Chigh monocytes that infiltrate atherosclerotic lesions. Circulation. 2012;125(2):364–74.PubMedCrossRef Robbins CS, Chudnovskiy A, Rauch PJ, Figueiredo JL, Iwamoto Y, Gorbatov R, Etzrodt M, Weber GF, Ueno T, van Rooijen N, Mulligan-Kehoe MJ. Extramedullary hematopoiesis generates Ly-6Chigh monocytes that infiltrate atherosclerotic lesions. Circulation. 2012;125(2):364–74.PubMedCrossRef
83.
Zurück zum Zitat Widlansky ME, Gokce N, Keaney JF, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol. 2003;42(7):1149–60.PubMedCrossRef Widlansky ME, Gokce N, Keaney JF, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol. 2003;42(7):1149–60.PubMedCrossRef
84.
Zurück zum Zitat Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol. 2000;20(9):2032–7.PubMedCrossRef Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol. 2000;20(9):2032–7.PubMedCrossRef
85.
Zurück zum Zitat Nisoli E, Carruba MO. Nitric oxide and mitochondrial biogenesis. J Cell Sci. 2006;119(14):2855–62.PubMedCrossRef Nisoli E, Carruba MO. Nitric oxide and mitochondrial biogenesis. J Cell Sci. 2006;119(14):2855–62.PubMedCrossRef
86.
Zurück zum Zitat Wang X, Cade R, Sun Z. Human eNOS gene delivery attenuates cold-induced elevation of blood pressure in rats. Am J Physiol Heart Circ Physiol. 2005;289(3):H1161-8.PubMedCrossRef Wang X, Cade R, Sun Z. Human eNOS gene delivery attenuates cold-induced elevation of blood pressure in rats. Am J Physiol Heart Circ Physiol. 2005;289(3):H1161-8.PubMedCrossRef
87.
Zurück zum Zitat Aquilano K, Baldelli S, Rotilio G, Ciriolo MR. Role of nitric oxide synthases in Parkinson’s disease: a review on the antioxidant and anti-inflammatory activity of polyphenols. Neurochem Res. 2008;33(12):2416–26.PubMedCrossRef Aquilano K, Baldelli S, Rotilio G, Ciriolo MR. Role of nitric oxide synthases in Parkinson’s disease: a review on the antioxidant and anti-inflammatory activity of polyphenols. Neurochem Res. 2008;33(12):2416–26.PubMedCrossRef
89.
Zurück zum Zitat Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L, LEAD-6 Study Group. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet. 2009;374(9683):39–47.PubMedCrossRef Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L, LEAD-6 Study Group. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet. 2009;374(9683):39–47.PubMedCrossRef
90.
Zurück zum Zitat Kim SJ, Nian C, Doudet DJ, McIntosh CH. Inhibition of dipeptidyl peptidase IV with sitagliptin (MK0431) prolongs islet graft survival in streptozotocin-induced diabetic mice. Diabetes. 2008;57(5):1331–9.PubMedCrossRef Kim SJ, Nian C, Doudet DJ, McIntosh CH. Inhibition of dipeptidyl peptidase IV with sitagliptin (MK0431) prolongs islet graft survival in streptozotocin-induced diabetic mice. Diabetes. 2008;57(5):1331–9.PubMedCrossRef
91.
Zurück zum Zitat Vinik A, Rafaeloff R, Pittenger G, Rosenberg L, Duguid W. Induction of pancreatic islet neogenesis. Horm Metab Res. 1997;29(06):278–93.PubMedCrossRef Vinik A, Rafaeloff R, Pittenger G, Rosenberg L, Duguid W. Induction of pancreatic islet neogenesis. Horm Metab Res. 1997;29(06):278–93.PubMedCrossRef
92.
Zurück zum Zitat Buse JB, Gumbiner B, Mathias NP, Nelson DM, Faja BW, Whitcomb RW, Troglitazone Insulin Study Group. Troglitazone use in insulin-treated type 2 diabetic patients. Diabetes Care. 1998;21(9):1455–61.PubMedCrossRef Buse JB, Gumbiner B, Mathias NP, Nelson DM, Faja BW, Whitcomb RW, Troglitazone Insulin Study Group. Troglitazone use in insulin-treated type 2 diabetic patients. Diabetes Care. 1998;21(9):1455–61.PubMedCrossRef
93.
Zurück zum Zitat Golay A, Guillet-Dauphiné N, Fendel A, Juges C, Assal JP. The insulin‐sparing effect of metformin in insulin‐treated diabetic patients. Diabetes Metab Res Rev. 1995;11(S1):63-7. Golay A, Guillet-Dauphiné N, Fendel A, Juges C, Assal JP. The insulin‐sparing effect of metformin in insulin‐treated diabetic patients. Diabetes Metab Res Rev. 1995;11(S1):63-7.
94.
Zurück zum Zitat DiSanto RM, Subramanian V, Gu Z. Recent advances in nanotechnology for diabetes treatment. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2015;7(4):548–64.PubMedPubMedCentralCrossRef DiSanto RM, Subramanian V, Gu Z. Recent advances in nanotechnology for diabetes treatment. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2015;7(4):548–64.PubMedPubMedCentralCrossRef
95.
Zurück zum Zitat Patra JK, Das G, Fraceto LF, Campos EV, del Pilar Rodriguez-Torres M, Acosta-Torres LS, Diaz-Torres LA, Grillo R, Swamy MK, Sharma S, Habtemariam S. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol. 2018;16(1):71.CrossRef Patra JK, Das G, Fraceto LF, Campos EV, del Pilar Rodriguez-Torres M, Acosta-Torres LS, Diaz-Torres LA, Grillo R, Swamy MK, Sharma S, Habtemariam S. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol. 2018;16(1):71.CrossRef
96.
Zurück zum Zitat Dhutia A. J. Research paper based on pathology lectures at Medlink 2007 and Vet-Medlink. 2007. Dhutia A. J. Research paper based on pathology lectures at Medlink 2007 and Vet-Medlink. 2007.
97.
Zurück zum Zitat Mo R, Jiang T, Di J, Tai W, Gu Z. Emerging micro-and nanotechnology based synthetic approaches for insulin delivery. Chem Soc Rev. 2014;43(10):3595–629.PubMedCrossRef Mo R, Jiang T, Di J, Tai W, Gu Z. Emerging micro-and nanotechnology based synthetic approaches for insulin delivery. Chem Soc Rev. 2014;43(10):3595–629.PubMedCrossRef
98.
Zurück zum Zitat Shah RV, Goldfine AB. Statins and risk of new-onset diabetes mellitus. Circulation. 2012;126(18):e282-4.PubMedCrossRef Shah RV, Goldfine AB. Statins and risk of new-onset diabetes mellitus. Circulation. 2012;126(18):e282-4.PubMedCrossRef
99.
Zurück zum Zitat Gæde P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348(5):383–93.PubMedCrossRef Gæde P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348(5):383–93.PubMedCrossRef
100.
Zurück zum Zitat Drummond RS, Lyall MJ, McKnight JA. Statins should be routinely prescribed in all adults with diabetes. Practical Diabetes Int. 2010;27(9):404–406a.CrossRef Drummond RS, Lyall MJ, McKnight JA. Statins should be routinely prescribed in all adults with diabetes. Practical Diabetes Int. 2010;27(9):404–406a.CrossRef
101.
Zurück zum Zitat Meier JJ, Bhushan A, Butler PC. The potential for stem cell therapy in diabetes. Pediatr Res. 2006;59(4):65–73.CrossRef Meier JJ, Bhushan A, Butler PC. The potential for stem cell therapy in diabetes. Pediatr Res. 2006;59(4):65–73.CrossRef
102.
Zurück zum Zitat Abdi R, Fiorina P, Adra CN, Atkinson M, Sayegh MH. Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes. Diabetes. 2008;57(7):1759–67.PubMedPubMedCentralCrossRef Abdi R, Fiorina P, Adra CN, Atkinson M, Sayegh MH. Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes. Diabetes. 2008;57(7):1759–67.PubMedPubMedCentralCrossRef
103.
Zurück zum Zitat Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, Coutinho M, Malmegrim KC, Foss-Freitas MC, Simoes BP, Foss MC. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2007;297(14):1568–76.PubMedCrossRef Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, Coutinho M, Malmegrim KC, Foss-Freitas MC, Simoes BP, Foss MC. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2007;297(14):1568–76.PubMedCrossRef
Metadaten
Titel
Dysregulation of nitric oxide synthases during early and late pathophysiological conditions of diabetes mellitus leads to amassing of microvascular impedement
verfasst von
Varuna Suresh
Amala Reddy
Publikationsdatum
21.04.2021
Verlag
Springer International Publishing
Erschienen in
Journal of Diabetes & Metabolic Disorders / Ausgabe 1/2021
Elektronische ISSN: 2251-6581
DOI
https://doi.org/10.1007/s40200-021-00799-y

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