Abstract
Aims/hypothesis: Under normal physiological conditions, glucagon signalling is important in glucose homeostasis. Hyperglucagonaemia or altered insulin:glucagon ratio plays a role in maintaining hyperglycaemia in subjects with type 2 diabetes. It has been reported that glucagon receptor knockout (Gcgr-/-) mice develop normally and have lower plasma glucose on a normal diet. The goal of the current research was to further investigate the role of glucagon signalling in metabolic control and glucose homeostasis. Methods: Gcgr-/- mice were challenged with a high-fat diet (HFD) and with streptozotocin, which induces beta cell damage. They were then analysed for whole-body and serum metabolic phenotypes as well as pancreatic islet morphology. Results: In comparison with wild-type mice, Gcgr-/- mice exhibited decreased body weight and food intake, reduced plasma glucose levels, and improved oral and intraperitoneal glucose tolerance. Elevated glucagon-like peptide-1 levels and reduced gastric emptying were also observed in Gcgr -/- mice, which also had reduced HFD-induced hyperinsulinaemia and hyperleptinaemia, and were resistant to the development of hepatic steatosis. In addition, Gcgr-/- mice were resistant to STZ-induced hyperglycaemia and pancreatic beta cell destruction. Conclusions/interpretation: This study demonstrates that blocking glucagon signalling by targeted Gcgr gene deletion leads to an improvement in metabolic control in this mouse model.
Original language | English (US) |
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Pages (from-to) | 142-150 |
Number of pages | 9 |
Journal | Diabetologia |
Volume | 50 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2007 |
Keywords
- Beta cell
- Gene knockout
- Glucagon receptor
- Metabolic control
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism