Reduced glucose-induced insulin secretion in low-protein-fed rats is associated with altered pancreatic islets redox status

J Cell Physiol. 2018 Jan;233(1):486-496. doi: 10.1002/jcp.25908. Epub 2017 May 3.

Abstract

In the present study, we investigated the relationship between early life protein malnutrition-induced redox imbalance, and reduced glucose-stimulated insulin secretion. After weaning, male Wistar rats were submitted to a normal-protein-diet (17%-protein, NP) or to a low-protein-diet (6%-protein, LP) for 60 days. Pancreatic islets were isolated and hydrogen peroxide (H2 O2 ), oxidized (GSSG) and reduced (GSH) glutathione content, CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and catalase (CAT) gene expression, as well as enzymatic antioxidant activities were quantified. Islets that were pre-incubated with H2 O2 and/or N-acetylcysteine, were subsequently incubated with glucose for insulin secretion measurement. Protein malnutrition increased CAT mRNA content by 100%. LP group SOD1 and CAT activities were 50% increased and reduced, respectively. H2 O2 production was more than 50% increased whereas GSH/GSSG ratio was near 60% lower in LP group. Insulin secretion was, in most conditions, approximately 50% lower in LP rat islets. When islets were pre-incubated with H2 O2 (100 μM), and incubated with glucose (33 mM), LP rats showed significant decrease of insulin secretion. This effect was attenuated when LP islets were exposed to N-acetylcysteine.

Keywords: antioxidant enzymes; insulin secretion; pancreatic islets; protein malnutrition; reactive oxygen species.

MeSH terms

  • Animal Nutritional Physiological Phenomena
  • Animals
  • Antioxidants / pharmacology
  • Blood Glucose / metabolism*
  • Catalase / genetics
  • Catalase / metabolism
  • Diet, Protein-Restricted*
  • Disease Models, Animal
  • Gene Expression Regulation, Enzymologic
  • Glutathione / metabolism
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Hydrogen Peroxide / metabolism
  • Insulin / blood*
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Male
  • Nutritional Status
  • Oxidation-Reduction
  • Oxidative Stress* / drug effects
  • Protein-Energy Malnutrition / blood
  • Protein-Energy Malnutrition / genetics
  • Protein-Energy Malnutrition / metabolism*
  • Protein-Energy Malnutrition / physiopathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Wistar
  • Superoxide Dismutase-1 / genetics
  • Superoxide Dismutase-1 / metabolism
  • Time Factors

Substances

  • Antioxidants
  • Blood Glucose
  • Insulin
  • RNA, Messenger
  • Hydrogen Peroxide
  • Catalase
  • Glutathione Peroxidase
  • Sod1 protein, rat
  • Superoxide Dismutase-1
  • Glutathione