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Erschienen in: Endocrine 1/2018

07.05.2018 | Original Article

Comparison of peripheral nerve protection between insulin-based glucose control and alpha lipoic acid (ALA) in the streptozotocin (STZ)-induced diabetic rat

verfasst von: Kyung Ae Lee, Na Young Lee, Tae Sun Park, Heung Yong Jin

Erschienen in: Endocrine | Ausgabe 1/2018

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Abstract

Strict glucose control is a well-proven therapeutic approach for peripheral neuropathies in patients with diabetes. Alpha lipoic acid (ALA) has also been accepted as a therapeutic agent for diabetic peripheral neuropathy (DPN) in the respect of pathogenesis. However, the potential of ALA as a treatment for DPN in comparison to that of glucose control is unclear. In this study, we compared the neuroprotective potential of glucose control and ALA. Animals were divided into 6 groups based on the intervention used, as follows: normal, diabetes (DM), DM+racemic form of ALA, DM+R form of ALA, DM+once daily insulin glargine, and DM+once daily insulin glargine with twice daily insulin glulisine. Various sensory tests were performed after 12 weeks of treatment, and immunohistochemistry of nerve fibers obtained from the sciatic and cutaneous nerves was performed after 24 weeks of treatment. There were no significant differences between the ALA-treated and insulin-treated DM groups in the sensory tests or in antioxidant activity. The axonal diameters and myelin sheath area of the sciatic nerves and the cutaneous small nerves, as assessed based on intraepidermal nerve fiber density, were similar in the ALA-treated and insulin-treated animals, although there was a non-significant trend for a mild increase in the both basal and rapid-acting insulin group compared with non-treated DM group. In conclusion, our results suggest that the neuroprotective benefits of ALA and insulin-based glucose control may be similar, although glucose control may have had slightly more beneficial effects in this animal model of diabetes. Of note, glucose levels should be strictly controlled, including corrections for fluctuations in the glucose level, to obtain therapeutic benefits in DPN.
Literatur
1.
2.
Zurück zum Zitat S. Tesfaye, A.J. Boulton, P.J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R.A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes care 33(10), 2285–2293 (2010)CrossRefPubMedCentralPubMed S. Tesfaye, A.J. Boulton, P.J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R.A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes care 33(10), 2285–2293 (2010)CrossRefPubMedCentralPubMed
3.
Zurück zum Zitat R. Pop-Busui, A.J. Boulton, E.L. Feldman, V. Bril, R. Freeman, R.A. Malik, J.M. Sosenko, D. Ziegler, Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes care 40(1), 136–154 (2017)CrossRefPubMed R. Pop-Busui, A.J. Boulton, E.L. Feldman, V. Bril, R. Freeman, R.A. Malik, J.M. Sosenko, D. Ziegler, Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes care 40(1), 136–154 (2017)CrossRefPubMed
4.
Zurück zum Zitat B.C. Callaghan, H.T. Cheng, C.L. Stables, A.L. Smith, E.L. Feldman, Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 11(6), 521–534 (2012)CrossRefPubMedCentralPubMed B.C. Callaghan, H.T. Cheng, C.L. Stables, A.L. Smith, E.L. Feldman, Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 11(6), 521–534 (2012)CrossRefPubMedCentralPubMed
5.
Zurück zum Zitat P.S. van Dam, Oxidative stress and diabetic neuropathy: pathophysiological mechanisms and treatment perspectives. Diabetes/Metab. Res. Rev. 18(3), 176–184 (2002)CrossRef P.S. van Dam, Oxidative stress and diabetic neuropathy: pathophysiological mechanisms and treatment perspectives. Diabetes/Metab. Res. Rev. 18(3), 176–184 (2002)CrossRef
6.
Zurück zum Zitat D. Ziegler, Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. Treat. Endocrinol. 3(3), 173–189 (2004)CrossRefPubMed D. Ziegler, Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. Treat. Endocrinol. 3(3), 173–189 (2004)CrossRefPubMed
7.
Zurück zum Zitat H.Y. Jin, S.J. Joung, J.H. Park, H.S. Baek, T.S. Park, The effect of alpha-lipoic acid on symptoms and skin blood flow in diabetic neuropathy. Diabet. Med. 24(9), 1034–1038 (2007)CrossRefPubMed H.Y. Jin, S.J. Joung, J.H. Park, H.S. Baek, T.S. Park, The effect of alpha-lipoic acid on symptoms and skin blood flow in diabetic neuropathy. Diabet. Med. 24(9), 1034–1038 (2007)CrossRefPubMed
8.
Zurück zum Zitat L. Rochette, S. Ghibu, A. Muresan, C. Vergely, Alpha-lipoic acid: molecular mechanisms and therapeutic potential in diabetes. Can. J. Physiol. Pharmacol. 93(12), 1021–1027 (2015)CrossRefPubMed L. Rochette, S. Ghibu, A. Muresan, C. Vergely, Alpha-lipoic acid: molecular mechanisms and therapeutic potential in diabetes. Can. J. Physiol. Pharmacol. 93(12), 1021–1027 (2015)CrossRefPubMed
9.
Zurück zum Zitat R. Najafi, A.M. Sharifi, A. Hosseini, Protective effects of alpha lipoic acid on high glucose-induced neurotoxicity in PC12 cells. Metab. brain Dis. 30(3), 731–738 (2015)CrossRefPubMed R. Najafi, A.M. Sharifi, A. Hosseini, Protective effects of alpha lipoic acid on high glucose-induced neurotoxicity in PC12 cells. Metab. brain Dis. 30(3), 731–738 (2015)CrossRefPubMed
10.
Zurück zum Zitat N. Papanas, D. Ziegler, Efficacy of alpha-lipoic acid in diabetic neuropathy. Expert Opin. Pharmacother. 15(18), 2721–2731 (2014)CrossRefPubMed N. Papanas, D. Ziegler, Efficacy of alpha-lipoic acid in diabetic neuropathy. Expert Opin. Pharmacother. 15(18), 2721–2731 (2014)CrossRefPubMed
11.
Zurück zum Zitat H.Y. Jin, K.A. Lee, J.Z. Wu, H.S. Baek, T.S. Park, The neuroprotective benefit from pioglitazone (PIO) addition on the alpha lipoic acid (ALA)-based treatment in experimental diabetic rats. Endocrine 47(3), 772–782 (2014)CrossRefPubMed H.Y. Jin, K.A. Lee, J.Z. Wu, H.S. Baek, T.S. Park, The neuroprotective benefit from pioglitazone (PIO) addition on the alpha lipoic acid (ALA)-based treatment in experimental diabetic rats. Endocrine 47(3), 772–782 (2014)CrossRefPubMed
12.
Zurück zum Zitat H.Y. Jin, S.H. Kim, H.M. Yu, H.S. Baek, T.S. Park, Therapeutic Potential of Dioscorea Extract (DA-9801) in Comparison with Alpha Lipoic Acid on the Peripheral Nerves in Experimental Diabetes. J. Diabetes Res. 2013, 631218 (2013)CrossRefPubMedCentralPubMed H.Y. Jin, S.H. Kim, H.M. Yu, H.S. Baek, T.S. Park, Therapeutic Potential of Dioscorea Extract (DA-9801) in Comparison with Alpha Lipoic Acid on the Peripheral Nerves in Experimental Diabetes. J. Diabetes Res. 2013, 631218 (2013)CrossRefPubMedCentralPubMed
13.
Zurück zum Zitat DCCT Research Group, Effect of intensive diabetes treatment on nerve conduction in the Diabetes Control and Complications Trial. Ann. Neurol. 38(6), 869–880 (1995) DCCT Research Group, Effect of intensive diabetes treatment on nerve conduction in the Diabetes Control and Complications Trial. Ann. Neurol. 38(6), 869–880 (1995)
14.
Zurück zum Zitat T. Linn, K. Ortac, H. Laube, K. Federlin, Intensive therapy in adult insulin-dependent diabetes mellitus is associated with improved insulin sensitivity and reserve: a randomized, controlled, prospective study over 5 years in newly diagnosed patients. Metabolism 45(12), 1508–1513 (1996)CrossRefPubMed T. Linn, K. Ortac, H. Laube, K. Federlin, Intensive therapy in adult insulin-dependent diabetes mellitus is associated with improved insulin sensitivity and reserve: a randomized, controlled, prospective study over 5 years in newly diagnosed patients. Metabolism 45(12), 1508–1513 (1996)CrossRefPubMed
15.
Zurück zum Zitat F. Ismail-Beigi, T. Craven, M.A. Banerji, J. Basile, J. Calles, R.M. Cohen, R. Cuddihy, W.C. Cushman, S. Genuth, R.H. Grimm Jr., B.P. Hamilton, B. Hoogwerf, D. Karl, L. Katz, A. Krikorian, P. O’Connor, R. Pop-Busui, U. Schubart, D. Simmons, H. Taylor, A. Thomas, D. Weiss, I. Hramiak, Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet 376(9739), 419–430 (2010)CrossRefPubMedCentralPubMed F. Ismail-Beigi, T. Craven, M.A. Banerji, J. Basile, J. Calles, R.M. Cohen, R. Cuddihy, W.C. Cushman, S. Genuth, R.H. Grimm Jr., B.P. Hamilton, B. Hoogwerf, D. Karl, L. Katz, A. Krikorian, P. O’Connor, R. Pop-Busui, U. Schubart, D. Simmons, H. Taylor, A. Thomas, D. Weiss, I. Hramiak, Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet 376(9739), 419–430 (2010)CrossRefPubMedCentralPubMed
16.
Zurück zum Zitat A.B. Oyenihi, A.O. Ayeleso, E. Mukwevho, B. Masola, Antioxidant strategies in the management of diabetic neuropathy. BioMed. Res. Int. 2015, 515042 (2015)CrossRefPubMedCentralPubMed A.B. Oyenihi, A.O. Ayeleso, E. Mukwevho, B. Masola, Antioxidant strategies in the management of diabetic neuropathy. BioMed. Res. Int. 2015, 515042 (2015)CrossRefPubMedCentralPubMed
17.
Zurück zum Zitat K. Fujiwara, K. Okamura-Ikeda, Y. Motokawa, Lipoylation of acyltransferase components of alpha-ketoacid dehydrogenase complexes. J. Biol. Chem. 271(22), 12932–12936 (1996)CrossRefPubMed K. Fujiwara, K. Okamura-Ikeda, Y. Motokawa, Lipoylation of acyltransferase components of alpha-ketoacid dehydrogenase complexes. J. Biol. Chem. 271(22), 12932–12936 (1996)CrossRefPubMed
18.
Zurück zum Zitat D.J. Keith, J.A. Butler, B. Bemer, B. Dixon, S. Johnson, M. Garrard, D.L. Sudakin, J.M. Christensen, C. Pereira, T.M. Hagen, Age and gender dependent bioavailability of R- and R,S-alpha-lipoic acid: a pilot study. Pharmacol. Res. 66(3), 199–206 (2012)CrossRefPubMedCentralPubMed D.J. Keith, J.A. Butler, B. Bemer, B. Dixon, S. Johnson, M. Garrard, D.L. Sudakin, J.M. Christensen, C. Pereira, T.M. Hagen, Age and gender dependent bioavailability of R- and R,S-alpha-lipoic acid: a pilot study. Pharmacol. Res. 66(3), 199–206 (2012)CrossRefPubMedCentralPubMed
19.
Zurück zum Zitat M. Brufani, R. Figliola, R)-alpha-lipoic acid oral liquid formulation: pharmacokinetic parameters and therapeutic efficacy. Acta bio-Med. 85(2), 108–115 (2014) M. Brufani, R. Figliola, R)-alpha-lipoic acid oral liquid formulation: pharmacokinetic parameters and therapeutic efficacy. Acta bio-Med. 85(2), 108–115 (2014)
20.
Zurück zum Zitat M. Nagamatsu, K.K. Nickander, J.D. Schmelzer, A. Raya, D.A. Wittrock, H. Tritschler, P.A. Low, Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes care 18(8), 1160–1167 (1995)CrossRefPubMed M. Nagamatsu, K.K. Nickander, J.D. Schmelzer, A. Raya, D.A. Wittrock, H. Tritschler, P.A. Low, Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes care 18(8), 1160–1167 (1995)CrossRefPubMed
21.
Zurück zum Zitat K.K. Nickander, B.R. McPhee, P.A. Low, H. Tritschler, Alpha-lipoic acid: antioxidant potency against lipid peroxidation of neural tissues in vitro and implications for diabetic neuropathy. Free Radic. Biol. Med. 21(5), 631–639 (1996)CrossRefPubMed K.K. Nickander, B.R. McPhee, P.A. Low, H. Tritschler, Alpha-lipoic acid: antioxidant potency against lipid peroxidation of neural tissues in vitro and implications for diabetic neuropathy. Free Radic. Biol. Med. 21(5), 631–639 (1996)CrossRefPubMed
22.
Zurück zum Zitat M.J. Stevens, I. Obrosova, X. Cao, C. Van Huysen, D.A. Greene, Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy. Diabetes 49(6), 1006–1015 (2000)CrossRefPubMed M.J. Stevens, I. Obrosova, X. Cao, C. Van Huysen, D.A. Greene, Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy. Diabetes 49(6), 1006–1015 (2000)CrossRefPubMed
23.
Zurück zum Zitat D. Ziegler, F.A. Gries, Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes 46(Suppl 2), S62–S66 (1997)CrossRefPubMed D. Ziegler, F.A. Gries, Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes 46(Suppl 2), S62–S66 (1997)CrossRefPubMed
24.
Zurück zum Zitat I.B. Hirsch, Glycemic variability and diabetes complications: does it matter? of course it does! Diabetes care 38(8), 1610–1614 (2015)CrossRefPubMed I.B. Hirsch, Glycemic variability and diabetes complications: does it matter? of course it does! Diabetes care 38(8), 1610–1614 (2015)CrossRefPubMed
25.
Zurück zum Zitat H.Y. Jin, K.A. Lee, T.S. Park, The impact of glycemic variability on diabetic peripheral neuropathy. Endocrine 53(3), 643–648 (2016)CrossRefPubMed H.Y. Jin, K.A. Lee, T.S. Park, The impact of glycemic variability on diabetic peripheral neuropathy. Endocrine 53(3), 643–648 (2016)CrossRefPubMed
Metadaten
Titel
Comparison of peripheral nerve protection between insulin-based glucose control and alpha lipoic acid (ALA) in the streptozotocin (STZ)-induced diabetic rat
verfasst von
Kyung Ae Lee
Na Young Lee
Tae Sun Park
Heung Yong Jin
Publikationsdatum
07.05.2018
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 1/2018
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-018-1613-5

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