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

Nat Rev Endocrinol. 2015 Jun;11(6):329-38. doi: 10.1038/nrendo.2015.51. Epub 2015 Apr 7.


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.

Publication types

  • Review

MeSH terms

  • Adipose Tissue / metabolism
  • Blood Glucose / metabolism*
  • Brain / metabolism
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism*
  • Energy Metabolism / physiology*
  • Glucagon / metabolism*
  • Glucagon / physiology
  • Glucagon / therapeutic use
  • Glucagon-Secreting Cells / metabolism*
  • Glucagon-Secreting Cells / physiology
  • Homeostasis*
  • Hormones / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use
  • Liver / metabolism
  • Myocardium / metabolism


  • Blood Glucose
  • Hormones
  • Hypoglycemic Agents
  • Insulin
  • Glucagon