Lack of glucagon receptor signaling and its implications beyond glucose homeostasis

Maureen J. Charron, Patricia M. Vuguin

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Glucagon action is transduced by a G protein-coupled receptor located in liver, kidney, intestinal smooth muscle, brain, adipose tissue, heart, pancreatic β-cells, and placenta. Genetically modified animal models have provided important clues about the role of glucagon and its receptor (Gcgr) beyond glucose control. The PubMed database was searched for articles published between 1995 and 2014 using the key terms glucagon, glucagon receptor, signaling, and animal models. Lack of Gcgr signaling has been associated with: i) hypoglycemic pregnancies, altered placentation, poor fetal growth, and increased fetal-neonatal death; ii) pancreatic glucagon cell hyperplasia and hyperglucagonemia; iii) altered body composition, energy state, and protection from diet-induced obesity; iv) impaired hepatocyte survival; v) altered glucose, lipid, and hormonal milieu; vi) altered metabolic response to prolonged fasting and exercise; vii) reduced gastric emptying and increased intestinal length; viii) altered retinal function; and ix) prevention of the development of diabetes in insulin-deficient mice. Similar phenotypic findings were observed in the hepatocyte-specific deletion of Gcgr. Glucagon action has been involved in the modulation of sweet taste responsiveness, inotropic and chronotropic effects in the heart, satiety, glomerular filtration rate, secretion of insulin, cortisol, ghrelin, GH, glucagon, and somatostatin, and hypothalamic signaling to suppress hepatic glucose production. Glucagon (α) cells under certain conditions can transdifferentiate into insulin (β) cells. These findings suggest that glucagon signaling plays an important role in multiple organs. Thus, treatment options designed to block Gcgr activation in diabetics may have implications beyond glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)R123-R130
JournalJournal of Endocrinology
Volume224
Issue number3
DOIs
StatePublished - 2015

Fingerprint

Glucagon Receptors
Glucagon
Homeostasis
Glucose
Insulin
Hepatocytes
Animal Models
Placentation
Genetically Modified Animals
Ghrelin
Fetal Death
Gastric Emptying
Liver
G-Protein-Coupled Receptors
Fetal Development
Body Composition
Somatostatin
Glomerular Filtration Rate
Hypoglycemic Agents
PubMed

Keywords

  • Glucagon cells
  • Pancreas

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Lack of glucagon receptor signaling and its implications beyond glucose homeostasis. / Charron, Maureen J.; Vuguin, Patricia M.

In: Journal of Endocrinology, Vol. 224, No. 3, 2015, p. R123-R130.

Research output: Contribution to journalArticle

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