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Advanced glycation end products impair glucose-induced insulin secretion from rat pancreatic β-cells

Hiroyuki Hachiya1, Yoshikazu Miura, Ken-Ichi Inoue

  • 1Second Department of Surgery, Dokkyo Medical University, School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, Japan. hachiya8@dokkyomed.ac.jp.

Journal of Hepato-Biliary-Pancreatic Sciences
|June 27, 2013
PubMed
Abstract

Insights

Advanced glycation end products (AGEs) impact insulin secretion. Glucose-derived AGEs (Glu-AGEs) and glyceraldehyde-derived AGEs (Glycer-AGEs) similarly inhibit insulin release, affecting malate dehydrogenase gene expression.

Area of Science:

  • Endocrinology
  • Metabolic Research
  • Molecular Biology

Background:

  • Advanced glycation end products (AGEs) are formed via non-enzymatic glycosylation and oxidation.
  • Glyceraldehyde-derived AGEs (Glycer-AGEs) exhibit greater toxicity than glucose-derived AGEs (Glu-AGEs).
  • The comparative effects of Glu-AGEs and Glycer-AGEs on insulin secretion require further investigation.

Purpose of the Study:

  • To compare the impact of Glu-AGEs and Glycer-AGEs on insulin secretion from rat pancreatic islets.
  • To identify molecular mechanisms underlying AGE-induced defects in insulin secretion.
  • To evaluate the efficacy of various rescue strategies in mitigating AGE-induced insulin secretion inhibition.

Main Methods:

  • Rat pancreatic islets were isolated and cultured with BSA, Glu-AGE-albumin, or Glycer-AGE-albumin.
  • Insulin secretion was measured following high glucose stimulation.
  • Rescue experiments and mRNA expression analysis of key genes were performed.

Main Results:

  • Both Glu-AGEs and Glycer-AGEs significantly reduced glucose-stimulated insulin secretion compared to BSA.
  • Insulin secretion defects were partially rescued by high extracellular potassium, tolbutamide, and α-ketoisocaproic acid.
  • AGEs decreased the mRNA expression of malate dehydrogenase (Mdh1/2), crucial for the NADH shuttle.

Conclusions:

  • Glycer-AGEs exhibit similar inhibitory effects on insulin secretion as Glu-AGEs, despite differing toxicity profiles.
  • AGEs impair insulin secretion through mechanisms involving the malate dehydrogenase gene.
  • Specific interventions can partially restore insulin secretion impaired by AGEs.
Keywords:
Advanced glycation end products · Insulin secretion · Nicotinamide adenine dinucleotide shuttle

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