Glucagon receptor knockout mice are resistant to diet-induced obesity and streptozotocin-mediated beta cell loss and hyperglycaemia

S. L. Conarello, G. Jiang, J. Mu, Z. Li, J. Woods, E. Zycband, J. Ronan, F. Liu, R. Sinha Roy, L. Zhu, M. J. Charron, B. B. Zhang

Research output: Contribution to journalArticlepeer-review

168 Scopus citations


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 languageEnglish (US)
Pages (from-to)142-150
Number of pages9
Issue number1
StatePublished - Jan 2007


  • Beta cell
  • Gene knockout
  • Glucagon receptor
  • Metabolic control

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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