Glucagon physiology and pathophysiology in the light of new advances

Research output: Contribution to journalArticle

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Abstract

Recent advances in the understanding of glucagoninsulin relationships at the level of the islets of Langerhans and of hepatic fuel metabolism are reviewed and their impact on our understanding of glucagon physiology and pathophysiology is considered. It now appears that α cells can respond directly to hyperglycaemia in the absence of insulin and β cells, but that antecedent hyperglycaemia masks or attenuates this response. Insulin appears to exert ongoing release inhibition upon glucagon secretion, probably via the intra-islet microvascular system that connects β cells to α cells. Diabetic hyperglucagonemia in insulin deficient states appears to be secondary to lack of the restraining influence of insulin. The α cell response to glucopenia, by contrast, may be in large part mediated by release of noradrenaline from nerve endings in contact with α cells. Glucagon's action on glucose and ketone production by hepatocytes is mediated by increase in cyclic-AMP-dependent protein kinase. The opposing action of insulin upon glucagon-mediated events probably occurs largely at this level. Consequently, when glucagon secretion or action is blocked, cyclic-AMP-dependent protein kinase activity is low even in the absence of insulin, explaining why marked glucose and ketone production is absent in bihormonal deficiency states.

Original languageEnglish (US)
Pages (from-to)574-578
Number of pages5
JournalDiabetologia
Volume28
Issue number8
DOIs
StatePublished - Aug 1985

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Glucagon
Insulin
Cyclic AMP-Dependent Protein Kinases
Ketones
Hyperglycemia
Glucose
Nerve Endings
Masks
Islets of Langerhans
Hepatocytes
Norepinephrine
Liver

Keywords

  • cyclic AMP-dependent protein kinase
  • diabetes
  • fructose-2,6-bisphosphate
  • Glucagon
  • insulin
  • noradrenaline

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Glucagon physiology and pathophysiology in the light of new advances. / Unger, Roger H.

In: Diabetologia, Vol. 28, No. 8, 08.1985, p. 574-578.

Research output: Contribution to journalArticle

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