Problem or solution: The strange story of glucagon

Peptides. 2018 Feb:100:36-41. doi: 10.1016/j.peptides.2017.11.013.

Abstract

Globally, 13% of the world's adult population is obese, and more than 400 million people suffer from diabetes. These conditions are both associated with significant morbidity, mortality and financial cost. Therefore, finding new pharmacological treatments is an imperative. Relative hyperglucagonaemia is seen in all types of diabetes, and has been implicated in its pathogenesis. Consequently, clinical trials are underway using drugs which block glucagon activity to treat type 2 diabetes. Conversely, exogenous glucagon can increase energy expenditure. Therefore, researchers are designing peptides that combine activation of the glucagon receptor with further incretin properties, which will treat obesity while mitigating the hyperglycaemic effects of glucagon. This review will discuss these conflicting physiological properties of glucagon, and the attempts to harness these effects pharmacologically.

Keywords: Diabetes; Energy expenditure; Glucagon; Incretin; Obesity; Oxyntomodulin.

Publication types

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

MeSH terms

  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Energy Metabolism / drug effects
  • Glucagon / metabolism
  • Glucagon / therapeutic use*
  • Humans
  • Hyperglycemia / complications
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / metabolism
  • Incretins / metabolism
  • Incretins / therapeutic use*
  • Insulin / metabolism
  • Insulin / therapeutic use
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Receptors, Glucagon / chemistry
  • Receptors, Glucagon / genetics

Substances

  • Incretins
  • Insulin
  • Receptors, Glucagon
  • Glucagon