Islet α cells and glucagon--critical regulators of energy homeostasis.

Published

Journal Article (Review)

Glucagon is secreted from islet α cells and controls blood levels of glucose in the fasting state. Impaired glucagon secretion predisposes some patients with type 1 diabetes mellitus (T1DM) to hypoglycaemia; whereas hyperglycaemia in patients with T1DM or type 2 diabetes mellitus (T2DM) is often associated with hyperglucagonaemia. Hence, therapeutic strategies to safely achieve euglycaemia in patients with diabetes mellitus now encompass bihormonal approaches to simultaneously deliver insulin and glucagon (in patients with T1DM) or reduce excess glucagon action (in patients with T1DM or T2DM). Glucagon also reduces food intake and increases energy expenditure through central and peripheral mechanisms, which suggests that activation of signalling through the glucagon receptor might be useful for controlling body weight. Here, we review new data that is relevant to understanding α-cell biology and glucagon action in the brain, liver, adipose tissue and heart, with attention to normal physiology, as well as conditions associated with dysregulated glucagon action. The feasibility and safety of current and emerging glucagon-based therapies that encompass both gain-of-function and loss-of-function approaches for the treatment of T1DM, T2DM and obesity is discussed in addition to developments, challenges and critical gaps in our knowledge that require additional investigation.

Full Text

Duke Authors

Cited Authors

  • Campbell, JE; Drucker, DJ

Published Date

  • June 2015

Published In

Volume / Issue

  • 11 / 6

Start / End Page

  • 329 - 338

PubMed ID

  • 25850661

Pubmed Central ID

  • 25850661

Electronic International Standard Serial Number (EISSN)

  • 1759-5037

International Standard Serial Number (ISSN)

  • 1759-5029

Digital Object Identifier (DOI)

  • 10.1038/nrendo.2015.51

Language

  • eng