The role of dysregulated glucagon secretion in type 2 diabetes.

Published

Journal Article (Review)

Excessive production of glucose by the liver contributes to fasting and postprandial hyperglycaemia, hallmarks of type 2 diabetes. A central feature of this pathologic response is insufficient hepatic insulin action, due to a combination of insulin resistance and impaired β-cell function. However, a case can be made that glucagon also plays a role in dysregulated hepatic glucose production and abnormal glucose homeostasis. Plasma glucagon concentrations are inappropriately elevated in diabetic individuals, and α-cell suppression by hyperglycaemia is blunted. Experimental evidence suggests that this contributes to greater rates of hepatic glucose production in the fasting state and attenuated reduction after meals. Recent studies in animal models indicate that reduction of glucagon action can have profound effects to mitigate hyperglycaemia even in the face of severe hypoinsulinaemia. While there are no specific treatments for diabetic patients yet available that act specifically on the glucagon signalling pathway, newer agents including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors reduce plasma glucagon and this is thought to contribute to their action to lower blood glucose. The α-cell and glucagon receptor remain tempting targets for novel diabetes treatments, but it is important to understand the magnitude of benefit new strategies would provide as preclinical models suggest that chronic interference with glucagon action could entail adverse effects as well.

Full Text

Duke Authors

Cited Authors

  • D'Alessio, D

Published Date

  • October 2011

Published In

Volume / Issue

  • 13 Suppl 1 /

Start / End Page

  • 126 - 132

PubMed ID

  • 21824266

Pubmed Central ID

  • 21824266

Electronic International Standard Serial Number (EISSN)

  • 1463-1326

International Standard Serial Number (ISSN)

  • 1462-8902

Digital Object Identifier (DOI)

  • 10.1111/j.1463-1326.2011.01449.x

Language

  • eng