Regulation of amino acid metabolism and α-cell proliferation by glucagon

Yoshitaka Hayashi, Yusuke Seino

Research output: Contribution to journalReview article

12 Citations (Scopus)

Abstract

Both glucagon and glucagon-like peptide-1 (GLP-1) are produced from proglucagon through proteolytic cleavage. Blocking glucagon action increases the circulating levels of glucagon and GLP-1, reduces the blood glucose level, and induces the proliferation of islet α-cells. Glucagon blockade also suppresses hepatic amino acid catabolism and increases the serum amino acid level. In animal models defective in both glucagon and GLP-1, the blood glucose level is not reduced, indicating that GLP-1 is required for glucagon blockade to reduce the blood glucose level. In contrast, hyperplasia of α-cells and hyperaminoacidemia are observed in such animal models, indicating that GLP-1 is not required for the regulation of α-cell proliferation or amino acid metabolism. These findings suggest that the regulation of amino acid metabolism is a more important specific physiological role of glucagon than the regulation of glucose metabolism. Although the effects of glucagon deficiency on glucose metabolism are compensated by the suppression of insulin secretion, the effects on amino acid metabolism are not. Recently, data showing a feedback regulatory mechanism between the liver and islet α-cells, which is mediated by glucagon and amino acids, are accumulating. However, a number of questions on the mechanism of this regulation remain to be addressed. The profile of glucagon as a regulator of amino acid metabolism must be carefully considered for glucagon blockade to be applied therapeutically in the treatment of patients with diabetes.

Original languageEnglish
Pages (from-to)464-472
Number of pages9
JournalJournal of Diabetes Investigation
Volume9
Issue number3
DOIs
Publication statusPublished - 05-2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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