Novel insight into glucagon receptor action: Lessons from knockout and transgenic mouse models

P. M. Vuguin, M. J. Charron

Research output: Contribution to journalReview article

28 Scopus citations

Abstract

Using knockout and transgenic technology, genetically modified animal models allowed us to understand the role of glucagon signalling in metabolism. Mice with a global deletion of the glucagon receptor gene (Gcgr) were designed using gene targeting. The phenotype of Gcgr-/-mouse provided important clues about the role of Gcgr in foetal growth, pancreatic development and glucose and lipid homeostasis. The lack of Gcgr activation was associated with: (i) hypoglycaemic pregnancies, poor foetal growth and increased foetal-neonatal demise; (ii) altered cytoarchitecture of pancreatic islets; (iii) altered glucose, lipid and hormonal milieu; (iv) reduced gastric emptying; (v) altered body composition and protection from diet-induced obesity; (vi) altered energy state; (vii) impaired hepatocyte survival; (viii) altered metabolic response to prolonged fasting and exercise and (ix) prevented development of diabetes in insulin-deficient mice. In contrast, mice overexpressing the Gcgr on pancreatic β-cells displayed an increase insulin secretion, pancreatic insulin content and β-cell mass, and partially protected against hyperglycaemia and impaired glucose tolerance when fed a high-fat diet. These findings suggest that glucagon signalling plays a significant role in the regulation of glucose and lipid homeostasis. Treatment options designed to block Gcgr activation may have negative implications in the treatment of diabetes.

Original languageEnglish (US)
Pages (from-to)144-150
Number of pages7
JournalDiabetes, Obesity and Metabolism
Volume13
Issue numberSUPPL. 1
DOIs
StatePublished - Oct 2011

Keywords

  • Diabetes
  • Gcgr knockout mouse model
  • Glucagon
  • Glucagon signalling
  • Hypoglycaemia
  • Islets
  • Pancreas

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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