Cited by 132Advanced Glycation End Products researchPancreatic function and diabetesDiabetes Treatment and Management

Advanced Glycation End Products Inhibit Glucose-Stimulated Insulin Secretion through Nitric Oxide-Dependent Inhibition of Cytochrome c Oxidase and Adenosine Triphosphate Synthesis

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Zhao, Zhengshan, Zhao, Chunying, Zhang, Xu Hannah, Zheng, Feng, Cai, Weijing, Vlassara, Helen, Ma, Zhongmin Alex·2009·Endocrinology

Abstract

Advanced glycation end products (AGEs) are implicated in diabetic complications. However, their role in β-cell dysfunction is less clear. In this study we examined the effects of AGEs on islet function in mice and in isolated islets. AGE-BSA or BSA was administered ip to normal mice twice a day for 2 wk. We showed that AGE-BSA-treated mice exhibited significantly higher glucose levels and lower insulin levels in response to glucose challenge than did BSA-treated mice, although there were no significant differences in insulin sensitivity and islet morphology between two groups. Glucose-stimulated insulin secretion by islets of the AGE-BSA-treated mice or AGE-BSA-treated normal islets was significantly lower than that by islets isolated from the BSA-treated mice or BSA-treated normal islets. Furthermore, AGE treatment of islet β-cells inhibited ATP production, and glimepiride, a sulfonylurea derivative, restored glucose-stimulated insulin secretion. Further investigation indicated that AGEs inhibited cytochrome c oxidase activity by inducing the expression of inducible nitric oxide synthase (iNOS). Blocking the formation of nitric oxide with an iNOS selective inhibitor aminoguanidine reversed the inhibitory effects of AGEs on ATP production and insulin secretion. We conclude that AGEs inhibit cytochrome c oxidase and ATP production, leading to the impairment of glucose-stimulated insulin secretion through iNOS-dependent nitric oxide production.

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Crossref · 10.1210/en.2008-1342

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Authors
Zhao, Z., Zhao, C., Zhang, X. H., Zheng, F., Cai, W., Vlassara, H., & Ma, Z. A.
Affiliations
Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Zhao, Zhengshan
Venue
Endocrinology
Published
2009-02-26
Volume
150
Issue
6
Pages
2569-2576
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
OpenAlex
W2081193499
Cited by
132
References
54
Citations by year
2025: 4 · 2024: 4 · 2023: 7 · 2022: 6 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 7 · 2017: 5 · 2016: 11 · 2015: 6 · 2014: 13 · 2013: 17 · 2012: 12
FWCI
7.03
Type
journal article
Language
en
Open access
Locations
  • Endocrinology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Diabetes Association
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK063076, R21DK074805, DK074805, DK063076)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
advanced glycation end products, glucose-stimulated insulin secretion, beta-cell dysfunction, cytochrome c oxidase, nitric oxide, inducible nitric oxide synthase, ATP production, islet function, diabetes complications, aminoguanidine, sulfonylureas, AGE-BSA
MeSH terms
Insulin Secretion, Adenosine Triphosphate, Animals, Cells, Cultured, Electron Transport Complex IV, Diabetes Mellitus, Disease Models, Animal, Female, Glucose, Insulin, Male, Mice, Inbred C57BL, Nitric Oxide, Glycation End Products, Advanced, Insulin-Secreting Cells, Mice, Nitric Oxide Synthase Type II

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