Upregulation of Alpha Cell Glucagon-Like Peptide 1 (GLP-1) in Psammomys Obesus--An Adaptive Response to Hyperglycaemia?

Diabetologia. 2011 Jun;54(6):1379-87. doi: 10.1007/s00125-011-2080-1. Epub 2011 Feb 25.

Abstract

Aims/hypothesis: The hormone glucagon-like peptide 1 (GLP-1) is released in response to a meal from the intestinal L-cells, where it is processed from proglucagon by the proconvertase (PC)1/3. In contrast, in the adult islets proglucagon is processed to glucagon by the PC2 enzyme. The aim of the study was to evaluate if, during the development of diabetes, alpha cells produce GLP-1 that, in turn, might trigger beta cell growth.

Methods: Beta cell mass, GLP-1 and insulin levels were measured in the gerbil Psammomys obesus (P. obesus), a rodent model of nutritionally induced diabetes. Furthermore, the presence of biologically active forms of GLP-1 and PC1/3 in alpha cells was demonstrated by immunofluorescence, and the release of GLP-1 from isolated P. obesus, mouse and human islets was investigated.

Results: During the development of diabetes in P. obesus, a significant increase in GLP-1 was detected in the portal vein (9.8 ± 1.5 vs 4.3 ± 0.7 pmol/l, p < 0.05), and in pancreas extracts (11.4 ± 2.2 vs 5.1 ± 1.3 pmol/g tissue, p < 0.05). Freshly isolated islets from hyperglycaemic animals released more GLP-1 following 24 h culture than islets from control animals (28.2 ± 4.4 pmol/l vs 5.8 ± 2.4, p < 0.01). GLP-1 release was increased from healthy P. obesus islets following culture in high glucose for 6 days (91 ± 9.1 pmol/l vs 28.8 ± 6.6, p < 0.01). High levels of GLP-1 were also found to be released from human islets. PC1/3 colocalised weakly with alpha cells.

Conclusions/interpretation: GLP-1 release from alpha cells is upregulated in P. obesus during the development of diabetes. A similar response is seen in islets exposed to high glucose, which supports the hypothesis that GLP-1 released from alpha cells promotes an increase in beta cell mass and function during metabolic challenge such as diabetes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / physiology
  • Adult
  • Animals
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Diabetes Mellitus / etiology
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / pathology
  • Diet / adverse effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Gerbillinae / metabolism*
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Secreting Cells / drug effects
  • Glucagon-Secreting Cells / metabolism*
  • Glucagon-Secreting Cells / pathology
  • Glucose / pharmacology
  • Humans
  • Hyperglycemia / metabolism*
  • Hyperglycemia / pathology
  • Insulin / metabolism
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Male
  • Mice
  • Middle Aged
  • Obesity / genetics
  • Obesity / metabolism*
  • Obesity / pathology
  • Up-Regulation / physiology*

Substances

  • Insulin
  • Glucagon-Like Peptide 1
  • Glucose