Endogenous advanced glycation end products in pancreatic islets after short-term carbohydrate intervention in obese, diabetes-prone mice

Nutr Diabetes. 2019 Mar 11;9(1):9. doi: 10.1038/s41387-019-0077-x.

Abstract

Diet-induced hyperglycemia is described as one major contributor to the formation of advanced glycation end products (AGEs) under inflammatory conditions, crucial in type 2 diabetes progression. Previous studies have indicated high postprandial plasma AGE-levels in diabetic patients and after long-term carbohydrate feeding in animal models. Pancreatic islets play a key role in glucose metabolism; thus, their susceptibility to glycation reactions due to high amounts of dietary carbohydrates is of special interest. Therefore, diabetes-prone New Zealand Obese (NZO) mice received either a carbohydrate-free, high-fat diet (CFD) for 11 weeks or were additionally fed with a carbohydrate-rich diet (CRD) for 7 days. In the CRD group, hyperglycemia and hyperinsulinemia were induced accompanied by increasing plasma 3-nitrotyrosine (3-NT) levels, higher amounts of 3-NT and inducible nitric oxide synthase (iNOS) within pancreatic islets. Furthermore, N-ε-carboxymethyllysine (CML) was increased in the plasma of CRD-fed NZO mice and substantially higher amounts of arg-pyrimidine, pentosidine and the receptor for advanced glycation end products (RAGE) were observed in pancreatic islets. These findings indicate that a short-term intervention with carbohydrates is sufficient to form endogenous AGEs in plasma and pancreatic islets of NZO mice under hyperglycemic and inflammatory conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diet, Carbohydrate-Restricted*
  • Diet, High-Fat*
  • Dietary Carbohydrates / administration & dosage*
  • Glycation End Products, Advanced / metabolism*
  • Hyperglycemia / metabolism
  • Insulin / blood
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans / metabolism*
  • Mice
  • Nitric Oxide Synthase Type II / metabolism
  • Obesity / metabolism*
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Blood Glucose
  • Dietary Carbohydrates
  • Glycation End Products, Advanced
  • Insulin
  • 3-nitrotyrosine
  • Tyrosine
  • Nitric Oxide Synthase Type II