Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Diabetology International
Erschienen in: Diabetology International 2/2017

23.01.2017 | Review Article

Lessons from basic pancreatic beta cell research in type-2 diabetes and vascular complications

verfasst von: Lena Eliasson, Jonathan Lou S. Esguerra, Anna Wendt

Erschienen in: Diabetology International | Ausgabe 2/2017

Einloggen, um Zugang zu erhalten

Abstract

The changes in life-style with increased access of food and reduced physical activity have resulted in the global epidemic of obesity. Consequently, individuals with type 2 diabetes and cardiovascular disease have also escalated. A central organ in the development of diabetes is the pancreas, and more specifically the pancreatic beta cells within the islets of Langerhans. Beta cells have been assigned the important task of secreting insulin when blood glucose is increased to lower the glucose level. An early sign of diabetes pathogenesis is lack of first phase insulin response and reduced second phase secretion. In this review, which is based on the foreign investigator award lecture given at the JSDC meeting in Sendai in October 2016, we discuss a possible cellular explanation for the reduced first phase insulin response and how this can be influenced by lipids. Moreover, since patients with cardiovascular disease and high levels of cholesterol are often treated with statins, we summarize recent data regarding effects on statins on glucose homeostasis and insulin secretion. Finally, we suggest microRNAs (miRNAs) as central players in the adjustment of beta cell function during the development of diabetes. We specifically discuss miRNAs regarding their involvement in insulin secretion regulation, differential expression in type 2 diabetes, and potential as biomarkers for prediction of diabetes and cardiovascular complications.
Literatur
1.
Barquera S, et al. Global overview of the epidemiology of atherosclerotic cardiovascular disease. Arch Med Res. 2015;46(5):328–38.PubMedCrossRef
2.
Halban PA, et al. Beta-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment. Diabetes Care. 2014;37(6):1751–8.PubMedPubMedCentralCrossRef
3.
Ashcroft FM, Rorsman P. Diabetes mellitus and the beta cell: the last ten years. Cell. 2012;148(6):1160–71.PubMedCrossRef
4.
Nicholls DG. The pancreatic beta-cell: a bioenergetic perspective. Physiol Rev. 2016;96(4):1385–447.PubMedCrossRef
5.
6.
Lang J. Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion. Eur J Biochem. 1999;259(1–2):3–17.PubMedCrossRef
7.
Eliasson L, et al. Rapid ATP-dependent priming of secretory granules precedes Ca(2 +)-induced exocytosis in mouse pancreatic B-cells. J Physiol. 1997;503(Pt 2):399–412.PubMedPubMedCentralCrossRef
8.
9.
Andersson SA, et al. Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes. Mol Cell Endocrinol. 2012;364(1–2):36–45.PubMedCrossRef
10.
Henquin JC. Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes. 2000;49(11):1751–60.PubMedCrossRef
11.
12.
Ammala C, et al. Exocytosis elicited by action potentials and voltage-clamp calcium currents in individual mouse pancreatic B-cells. J Physiol. 1993;472:665–88.PubMedPubMedCentralCrossRef
13.
Braun M, et al. Voltage-gated ion channels in human pancreatic beta-cells: electrophysiological characterization and role in insulin secretion. Diabetes. 2008;57(6):1618–28.PubMedCrossRef
14.
Leech CA, et al. Molecular physiology of glucagon-like peptide-1 insulin secretagogue action in pancreatic beta cells. Prog Biophys Mol Biol. 2011;107(2):236–47.PubMedPubMedCentralCrossRef
15.
Seino S, Shibasaki T, Minami K. Dynamics of insulin secretion and the clinical implications for obesity and diabetes. J Clin Investig. 2011;121(6):2118–25.PubMedPubMedCentralCrossRef
16.
Ganic E, et al. MafA-Controlled Nicotinic Receptor Expression Is Essential for Insulin Secretion and Is Impaired in Patients with Type 2 Diabetes. Cell Rep. 2016;14(8):1991–2002.PubMedCrossRef
17.
Kailey B, et al. SSTR2 is the functionally dominant somatostatin receptor in human pancreatic beta- and alpha-cells. Am J Physiol Endocrinol Metab. 2012;303(9):E1107–16.PubMedPubMedCentralCrossRef
18.
Straub SG, Sharp GW. Evolving insights regarding mechanisms for the inhibition of insulin release by norepinephrine and heterotrimeric G proteins. Am J Physiol Cell Physiol. 2012;302(12):C1687–98.PubMedPubMedCentralCrossRef
19.
Rosengren AH, et al. Reduced insulin exocytosis in human pancreatic beta-cells with gene variants linked to type 2 diabetes. Diabetes. 2012;61(7):1726–33.PubMedPubMedCentralCrossRef
20.
Tang Y, et al. Genotype-based treatment of type 2 diabetes with an alpha2A-adrenergic receptor antagonist. Sci Transl Med. 2014;6(257):257ra139.PubMedCrossRef
21.
Goto Y, Kakizaki M, Masaki N. Production of spontaneous diabetic rats by repetition of selective breeding. Tohoku J Exp Med. 1976;119(1):85–90.PubMedCrossRef
22.
Granhall C, et al. High-resolution quantitative trait locus analysis reveals multiple diabetes susceptibility loci mapped to intervals < 800 kb in the species-conserved Niddm1i of the GK rat. Genetics. 2006;174(3):1565–72.PubMedPubMedCentralCrossRef
23.
Curry DL, Bennett LL, Grodsky GM. Dynamics of insulin secretion by the perfused rat pancreas. Endocrinology. 1968;83(3):572–84.PubMedCrossRef
24.
Hosker JP, et al. Similar reduction of first- and second-phase B-cell responses at three different glucose levels in type II diabetes and the effect of gliclazide therapy. Metabolism. 1989;38(8):767–72.PubMedCrossRef
25.
Renstrom E, et al. Cooling inhibits exocytosis in single mouse pancreatic B-cells by suppression of granule mobilization. J Physiol. 1996;494(Pt 1):41–52.PubMedPubMedCentralCrossRef
26.
Renstrom E, Eliasson L, Rorsman P. Protein kinase A-dependent and -independent stimulation of exocytosis by cAMP in mouse pancreatic B-cells. J Physiol. 1997;502(Pt 1):105–18.PubMedPubMedCentralCrossRef
27.
Olofsson CS, et al. Fast insulin secretion reflects exocytosis of docked granules in mouse pancreatic B-cells. Pflugers Arch. 2002;444(1–2):43–51.PubMedCrossRef
28.
Takahashi N, et al. SNARE conformational changes that prepare vesicles for exocytosis. Cell Metab. 2010;12(1):19–29.PubMedCrossRef
29.
30.
Barg S, et al. Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification. J Cell Sci. 2001;114(Pt 11):2145–54.PubMed
31.
Vikman J, et al. Insulin secretion is highly sensitive to desorption of plasma membrane cholesterol. Faseb J. 2009;23(1):58–67.PubMedCrossRef
32.
Barg S, et al. The stimulatory action of tolbutamide on Ca2 + -dependent exocytosis in pancreatic beta cells is mediated by a 65-kDa mdr-like P-glycoprotein. Proc Natl Acad Sci USA. 1999;96(10):5539–44.PubMedPubMedCentralCrossRef
33.
Takahashi N, et al. Post-priming actions of ATP on Ca2 + -dependent exocytosis in pancreatic beta cells. Proc Natl Acad Sci USA. 1999;96(2):760–5.PubMedPubMedCentralCrossRef
34.
35.
Seino S, Shibasaki T. PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis. Physiol Rev. 2005;85(4):1303–42.PubMedCrossRef
36.
Eliasson L, et al. PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells. Science. 1996;271(5250):813–5.PubMedCrossRef
37.
Shibasaki T, et al. Cooperation between cAMP signalling and sulfonylurea in insulin secretion. Diabetes Obes Metab. 2014;16(Suppl 1):118–25.PubMedCrossRef
38.
Takahashi H, et al. Role of Epac2A/Rap1 signaling in interplay between incretin and sulfonylurea in insulin secretion. Diabetes. 2015;64(4):1262–72.PubMedCrossRef
39.
Edlund A, et al. CFTR and Anoctamin 1 (ANO1) contribute to cAMP amplified exocytosis and insulin secretion in human and murine pancreatic beta-cells. BMC Med. 2014;12:87.PubMedPubMedCentralCrossRef
40.
Bellin MD, et al. Insulin secretion improves in cystic fibrosis following ivacaftor correction of CFTR: a small pilot study. Pediatr Diabetes. 2013;14(6):417–21.PubMedPubMedCentralCrossRef
41.
Tsabari R, et al. CFTR potentiator therapy ameliorates impaired insulin secretion in CF patients with a gating mutation. J Cyst Fibros. 2016;15(3):e25–7.PubMedCrossRef
42.
Tomas A, et al. Munc 18-1 and granuphilin collaborate during insulin granule exocytosis. Traffic. 2008;9(5):813–32.PubMedCrossRef
43.
44.
Gandasi NR, Barg S. Contact-induced clustering of syntaxin and munc18 docks secretory granules at the exocytosis site. Nat Commun. 2014;5:3914.PubMedCrossRef
45.
Vikman J, et al. Truncation of SNAP-25 reduces the stimulatory action of cAMP on rapid exocytosis in insulin-secreting cells. Am J Physiol Endocrinol Metab. 2009;297(2):E452–61.PubMedCrossRef
46.
Gaisano HY, et al. Abnormal expression of pancreatic islet exocytotic soluble N-ethylmaleimide-sensitive factor attachment protein receptors in Goto-Kakizaki rats is partially restored by phlorizin treatment and accentuated by high glucose treatment. Endocrinology. 2002;143(11):4218–26.PubMedCrossRef
47.
Ostenson CG, et al. Impaired gene and protein expression of exocytotic soluble N-ethylmaleimide attachment protein receptor complex proteins in pancreatic islets of type 2 diabetic patients. Diabetes. 2006;55(2):435–40.PubMedCrossRef
48.
Taylor R. Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause. Diabetologia. 2008;51(10):1781–9.PubMedCrossRef
49.
Olofsson CS, et al. Palmitate increases L-type Ca2 + currents and the size of the readily releasable granule pool in mouse pancreatic beta-cells. J Physiol. 2004;557(Pt 3):935–48.PubMedPubMedCentralCrossRef
50.
Deeney JT, et al. Acute stimulation with long chain acyl-CoA enhances exocytosis in insulin-secreting cells (HIT T-15 and NMRI beta-cells). J Biol Chem. 2000;275(13):9363–8.PubMedCrossRef
51.
Salunkhe VA, et al. Dual effect of rosuvastatin on glucose homeostasis through improved insulin sensitivity and reduced insulin secretion. EBioMedicine. 2016;10:185–94.PubMedPubMedCentralCrossRef
52.
Olofsson CS, et al. Long-term exposure to glucose and lipids inhibits glucose-induced insulin secretion downstream of granule fusion with plasma membrane. Diabetes. 2007;56(7):1888–97.PubMedCrossRef
53.
Hoppa MB, et al. Chronic palmitate exposure inhibits insulin secretion by dissociation of Ca(2 +) channels from secretory granules. Cell Metab. 2009;10(6):455–65.PubMedPubMedCentralCrossRef
54.
55.
56.
Salaun C, Gould GW, Chamberlain LH. Lipid raft association of SNARE proteins regulates exocytosis in PC12 cells. J Biol Chem. 2005;280(20):19449–53.PubMedPubMedCentralCrossRef
57.
Nagaraj V, et al. Elevated basal insulin secretion in type 2 diabetes caused by reduced plasma membrane cholesterol. Mol Endocrinol. 2016;30(10):1059–69.PubMedPubMedCentralCrossRef
58.
Cochran BJ, et al. Impact of perturbed pancreatic beta-cell cholesterol homeostasis on adipose tissue and skeletal muscle metabolism. Diabetes. 2016;65(12):3610–20.PubMedCrossRef
59.
Nagao M, et al. Selective breeding of mice for different susceptibilities to high fat diet-induced glucose intolerance: development of two novel mouse lines, selectively bred diet-induced glucose intolerance-prone and -resistant. J Diabetes Investig. 2012;3(3):245–51.PubMedCrossRef
60.
Nagao M, et al. Characterization of pancreatic islets in two selectively bred mouse lines with different susceptibilities to high-fat diet-induced glucose intolerance. PLoS One. 2014;9(1):e84725.PubMedPubMedCentralCrossRef
61.
Ridker PM, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–207.PubMedCrossRef
62.
Cederberg H, et al. Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort. Diabetologia. 2015;58(5):1109–17.PubMedCrossRef
63.
Sattar N, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. The Lancet. 2010;375(9716):735–42.CrossRef
64.
65.
Buhaescu I, Izzedine H. Mevalonate pathway: a review of clinical and therapeutical implications. Clin Biochem. 2007;40(9–10):575–84.PubMedCrossRef
66.
Duvnjak L, Blaslov K. Statin treatment is associated with insulin sensitivity decrease in type 1 diabetes mellitus: a prospective, observational 56-month follow-up study. J Clin Lipidol. 2016;10(4):1004–10.PubMedCrossRef
67.
Okada K, et al. Pravastatin improves insulin resistance in dyslipidemic patients. J Atheroscler Thromb. 2005;12(6):322–9.PubMedCrossRef
68.
Güçlü F, et al. Effects of a statin group drug, pravastatin, on the insulin resistance in patients with metabolic syndrome. Biomed Pharmacother. 2004;58(10):614–8.PubMedCrossRef
69.
Navarese EP, et al. Meta-analysis of impact of different types and doses of statins on new-onset diabetes mellitus. Am J Cardiol. 2013;111(8):1123–30.PubMedCrossRef
70.
Bełtowski J, et al. Opposite effects of pravastatin and atorvastatin on insulin sensitivity in the rat: role of vitamin D metabolites. Atherosclerosis. 2011;219(2):526–31.PubMedCrossRef
71.
Fraulob Julio C, et al. Beneficial effects of rosuvastatin on insulin resistance, adiposity, inflammatory markers and non-alcoholic fatty liver disease in mice fed on a high-fat diet. Clin Sci. 2012;123(4):259–70.PubMedCrossRef
72.
Birnbaum Y, et al. PTEN upregulation may explain the development of insulin resistance and type 2 diabetes with high dose statins. Cardiovasc Drugs Ther. 2014;28(5):447–57.PubMedCrossRef
73.
Takaguri A, et al. Effects of atorvastatin and pravastatin on signal transduction related to glucose uptake in 3T3L1 adipocytes. J Pharmacol Sci. 2008;107(1):80–9.PubMedCrossRef
74.
Chamberlain LH. Inhibition of isoprenoid biosynthesis causes insulin resistance in 3T3-L1 adipocytes. FEBS Lett. 2001;507(3):357–61.PubMedCrossRef
75.
Nakata M, et al. Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control. Diabetologia. 2006;49(8):1881–92.PubMedCrossRef
76.
Zhao W, Zhao S-P. Different effects of statins on induction of diabetes mellitus: an experimental study. Drug Des Dev Ther. 2015;9:6211–23.CrossRef
77.
Naples M, et al. Effect of rosuvastatin on insulin sensitivity in an animal model of insulin resistance: evidence for statin-induced hepatic insulin sensitization. Atherosclerosis. 2008;198(1):94–103.PubMedCrossRef
78.
Li G, et al. Blockade of mevalonate production by lovastatin attenuates bombesin and vasopressin potentiation of nutrient-induced insulin secretion in HIT-T15 cells. Probable involvement of small GTP-binding proteins. Biochem J. 1993;289(Pt 2):379–85.PubMedPubMedCentralCrossRef
79.
Salunkhe VA, et al. Rosuvastatin treatment affects both basal and glucose-induced insulin secretion in INS-1 832/13 cells. PLoS One. 2016;11(3):e0151592.PubMedPubMedCentralCrossRef
80.
Yada T, et al. Inhibition by simvastatin, but not pravastatin, of glucose-induced cytosolic Ca2 + signalling and insulin secretion due to blockade of L-type Ca2 + channels in rat islet beta-cells. Br J Pharmacol. 1999;126(5):1205–13.PubMedPubMedCentralCrossRef
81.
Zhou J, et al. Effects of simvastatin on glucose metabolism in mouse MIN6 cells. J Diabetes Res. 2014;2014:10.
82.
Velasco M, et al. Modulation of ionic channels and insulin secretion by drugs and hormones in pancreatic beta cells. Mol Pharmacol. 2016;90(3):341–57.PubMedCrossRef
83.
Zúñiga-Hertz JP, et al. Distinct pathways of cholesterol biosynthesis impact on insulin secretion. J Endocrinol. 2015;224(1):75–84.PubMedCrossRef
84.
85.
Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature. 1990;343(6257):425–30.PubMedCrossRef
86.
87.
88.
Brault M, et al. Statin treatment and new-onset diabetes: a review of proposed mechanisms. Metabolism. 2014;63(6):735–45.PubMedCrossRef
89.
Swerdlow DI, et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet. 2015;385(9965):351–61.PubMedPubMedCentralCrossRef
90.
Sugiyama T, et al. Is there gluttony in the time of statins? different time trends of caloric and fat intake between statin-users and non-users among US adults. JAMA Intern Med. 2014;174(7):1038–45.PubMedPubMedCentralCrossRef
91.
92.
93.
Kloosterman WP, Plasterk RH. The diverse functions of microRNAs in animal development and disease. Dev Cell. 2006;11(4):441–50.PubMedCrossRef
94.
Guay C, et al. Diabetes mellitus, a microRNA-related disease? Transl Res. 2011;157(4):253–64.PubMedCrossRef
95.
Eliasson L, Esguerra JL. Role of non-coding RNAs in pancreatic beta-cell development and physiology. Acta Physiol (Oxf). 2014;211(2):273–84.CrossRef
96.
97.
Lynn FC, et al. MicroRNA expression is required for pancreatic islet cell genesis in the mouse. Diabetes. 2007;56(12):2938–45.PubMedCrossRef
98.
Martinez-Sanchez A, Nguyen-Tu MS, Rutter GA. DICER inactivation identifies pancreatic beta-Cell “Disallowed” genes targeted by microRNAs. Mol Endocrinol. 2015;29(7):1067–79.PubMedPubMedCentralCrossRef
99.
Melkman-Zehavi T, et al. miRNAs control insulin content in pancreatic beta-cells via downregulation of transcriptional repressors. EMBO J. 2011;30(5):835–45.PubMedPubMedCentralCrossRef
100.
101.
Poy MN, et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 2004;432(7014):226–30.PubMedCrossRef
102.
103.
104.
105.
Belgardt BF, et al. The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes. Nat Med. 2015;21(6):619–27.PubMedCrossRef
106.
Esguerra JL, et al. Regulation of pancreatic beta cell stimulus-secretion coupling by microRNAs. Genes (Basel). 2014;5(4):1018–31.
107.
Portha B, et al. The GK rat beta-cell: a prototype for the diseased human beta-cell in type 2 diabetes? Mol Cell Endocrinol. 2009;297(1–2):73–85.PubMedCrossRef
108.
Esguerra JL, et al. Differential glucose-regulation of microRNAs in pancreatic islets of non-obese type 2 diabetes model Goto-Kakizaki rat. PLoS One. 2011;6(4):e18613.PubMedPubMedCentralCrossRef
109.
Oh E, et al. Munc18-1 regulates first-phase insulin release by promoting granule docking to multiple syntaxin isoforms. J Biol Chem. 2012;287(31):25821–33.PubMedPubMedCentralCrossRef
110.
Shang J, et al. Induction of miR-132 and miR-212 expression by glucagon-like peptide 1 (GLP-1) in rodent and human pancreatic beta-Cells. Mol Endocrinol. 2015;29(9):1243–53.PubMedPubMedCentralCrossRef
111.
Malm HA, et al. Transcriptional regulation of the miR-212/miR-132 cluster in insulin-secreting beta-cells by cAMP-regulated transcriptional co-activator 1 and salt-inducible kinases. Mol Cell Endocrinol. 2016;424:23–33.PubMedCrossRef
112.
113.
Valadi H, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–9.PubMedCrossRef
114.
115.
Jalabert A, et al. Exosome-like vesicles released from lipid-induced insulin-resistant muscles modulate gene expression and proliferation of beta recipient cells in mice. Diabetologia. 2016;59(5):1049–58.PubMedCrossRef
116.
Ji X, et al. Plasma miR-208 as a biomarker of myocardial injury. Clin Chem. 2009;55(11):1944–9.PubMedCrossRef
117.
118.
Zampetaki A, et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010;107(6):810–7.PubMedCrossRef
119.
Zampetaki A, et al. Prospective study on circulating microRNAs and risk of myocardial infarction. J Am Coll Cardiol. 2012;60(4):290–9.PubMedCrossRef
120.
Zhang T, et al. Plasma miR-126 is a potential biomarker for early prediction of type 2 diabetes mellitus in susceptible individuals. Biomed Res Int. 2013;2013:761617.PubMedPubMedCentral
121.
Samandari N, et al. Circulating microRNA levels predict residual beta cell function and glycaemic control in children with type 1 diabetes mellitus. Diabetologia. 2016;60:354–63.PubMedCrossRef
122.
McManus DD, et al. Plasma microRNAs are associated with atrial fibrillation and change after catheter ablation (the miRhythm study). Heart Rhythm. 2015;12(1):3–10.PubMedCrossRef
123.
Guay C, Regazzi R. Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol. 2013;9(9):513–21.PubMedCrossRef
124.
Vegter EL, et al. MicroRNAs in heart failure: from biomarker to target for therapy. Eur J Heart Fail. 2016;18(5):457–68.PubMedCrossRef
125.
McDonald JS, et al. Analysis of circulating microRNA: preanalytical and analytical challenges. Clin Chem. 2011;57(6):833–40.PubMedCrossRef
126.
Tanriverdi K, et al. Comparison of RNA isolation and associated methods for extracellular RNA detection by high-throughput quantitative polymerase chain reaction. Anal Biochem. 2016;501:66–74.PubMedCrossRef
127.
Marabita F, et al. Normalization of circulating microRNA expression data obtained by quantitative real-time RT-PCR. Brief Bioinform. 2016;17(2):204–12.PubMedCrossRef
128.
Sun C, et al. miR-21 regulates triglyceride and cholesterol metabolism in non-alcoholic fatty liver disease by targeting HMGCR. Int J Mol Med. 2015;35(3):847–53.PubMed
Metadaten
Titel
Lessons from basic pancreatic beta cell research in type-2 diabetes and vascular complications
verfasst von
Lena Eliasson
Jonathan Lou S. Esguerra
Anna Wendt
Publikationsdatum
23.01.2017
Verlag
Springer Japan
Erschienen in
Diabetology International / Ausgabe 2/2017
Print ISSN: 2190-1678
Elektronische ISSN: 2190-1686
DOI
https://doi.org/10.1007/s13340-017-0304-4

Weitere Artikel der Ausgabe 2/2017

Diabetology International 2/2017 Zur Ausgabe

Original Article

High glycated albumin (GA) levels and the GA/HbA1c ratio in patients with insulin autoimmune syndrome

Report of the committee

Causes of death in Japanese patients with diabetes based on the results of a survey of 45,708 cases during 2001–2010: report of Committee on Causes of Death in Diabetes Mellitus

Erratum

Erratum to: Lessons from basic pancreatic beta cell research in type-2 diabetes and vascular complications

Original Article

The effects of ipragliflozin on the liver-to-spleen attenuation ratio as assessed by computed tomography and on alanine transaminase levels in Japanese patients with type 2 diabetes mellitus

Original Article

Effects of alogliptin on the ratio of glycated albumin to HbA1c in patients with type 2 diabetes mellitus

Original Article

Cognitive impairment in elderly patients with type 2 diabetes mellitus: prevalence and related clinical factors

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

17.04.2024 | DGIM 2024 | Nachrichten

Denken Sie bei starker Blutung auch an die Hemmkörper-Hämophilie

17.04.2024 | Mammakarzinom | Nachrichten

Adjuvante Brustkrebstherapie: Doppelt hält besser

17.04.2024 | Delir nicht substanzbedingt | Nachrichten

Delir kann Demenz begünstigen

16.04.2024 | Spondylitis ankylosans | Nachrichten

Vorsicht mit hohen NSAR-Dosen bei ankylosierender Spondylitis!
weitere anzeigen

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise