Alpha cell function in health and disease: influence of glucagon-like peptide-1

Diabetologia. 2005 Sep;48(9):1700-13. doi: 10.1007/s00125-005-1878-0. Epub 2005 Aug 13.

Abstract

Although there is abundant evidence that hyperglucagonaemia plays a key role in the development of hyperglycaemia in type 2 diabetes, efforts to understand and correct this abnormality have been overshadowed by the emphasis on insulin secretion and action. However, recognition that the incretin hormone glucagon-like peptide-1 (GLP-1) exerts opposing effects on glucagon and insulin secretion has revived interest in glucagon, the neglected partner of insulin, in the bihormonal hypothesis. In healthy subjects, glucagon secretion is regulated by a variety of nutrient, neural and hormonal factors, the most important of which is glucose. The defect in alpha cell function that occurs in type 2 diabetes reflects impaired glucose sensing. GLP-1 inhibits glucagon secretion in vitro and in vivo in experimental animals, and suppresses glucagon release in a glucose-dependent manner in healthy subjects. This effect is also evident in diabetic patients, but GLP-1 does not inhibit glucagon release in response to hypoglycaemia, and may even enhance it. Early clinical studies with agents acting through GLP-1 signalling mechanisms (e.g. exenatide, liraglutide and vildagliptin) suggest that GLP-1 can improve alpha cell glucose sensing in patients with type 2 diabetes. Therapeutic approaches based around GLP-1 have the potential to improve both alpha cell and beta cell function, and could be of benefit in patients with a broad range of metabolic disorders.

Publication types

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

MeSH terms

  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Glucagon / blood
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Humans
  • Insulin / physiology
  • Islets of Langerhans / physiology*
  • Islets of Langerhans / physiopathology*

Substances

  • Blood Glucose
  • Insulin
  • Glucagon