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Advanced Glycation End Products Impair Glucose-Induced Insulin Secretion From Rat Pancreatic β-cells

Advanced Glycation End Products Impair Glucose-Induced Insulin Secretion From Rat Pancreatic β-cells

Hiroyuki Hachiya, Yoshikazu Miura, Ken-Ichi Inoue, Kyung Hwa Park, Masayoshi Takeuchi, Keiichi Kubota

J Hepatobiliary Pancreat Sci. 2014 Feb;21(2):134-41.

PMID: 23798335

Abstract:

Background:
Advanced glycation end products (AGEs) are derivative compounds generated from non-enzymatic glycosylation and oxidation. In comparison with glucose-derived AGEs (Glu-AGEs), glyceraldehyde-derived AGEs (Glycer-AGEs) have stronger toxicity to living systems. In this study, we compared the effects of Glu-AGE and Glycer-AGE on insulin secretion.
Method:
Rat pancreatic islets were isolated by collagenase digestion and primary-cultured in the presence of 0.1 mg/ml bovine serum albumin (BSA) or 0.1 mg/ml Glu-AGE or Glycer-AGE-albumin. After 48 h of culture, we performed an insulin secretion test and identified the defects by a battery of rescue experiments [corrected]. Also, mRNA expression of genes associated with insulin secretion was measured.
Results:
Insulin secretion induced by a high glucose concentration was 164.1 ± 6.0, 124.4 ± 4.4 (P < 0.05) and 119.8 ± 7.1 (P < 0.05) μU/3 islets/h in the presence of BSA, Glu-AGE, and Glycer-AGE, respectively. Inhibition of insulin secretion by Glu-AGE or Glycer-AGE was rescued by a high extracellular potassium concentration, tolbutamide and α-ketoisocaproic acid, but not by glyceraldehyde, dihydroxacetone, methylpyruvate, glucagon-like peptide-1 and acetylcholine. Glu-AGE or Glycer-AGE reduced the expression of the malate dehydrogenase (Mdh1/2) gene, which plays a critical role in the nicotinamide adenine dinucleotide (NADH) shuttle.
Conclusion:
Despite its reported cytotoxicity, the effects of Glycer-AGE on insulin secretion are similar to those of Glu-AGE.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP7325168	Glycer(ol-d3)		7325-16-8	Price

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