TY - JOUR

T1 - Metabolic regulation of glucagon secretion

AU - Armour, Sarah L.

AU - Stanley, Jade E.

AU - Cantley, James

AU - Dean, E. Danielle

AU - Knudsen, Jakob G.

PY - 2023

Y1 - 2023

N2 - Since the discovery of glucagon 100 years ago, the hormone and the pancreatic islet alpha cells that produce it have remained enigmatic relative to insulin-producing beta cells. Canonically, alpha cells have been described in the context of glucagon's role in glucose metabolism in liver, with glucose as the primary nutrient signal regulating alpha cell function. However, current data reveal a more holistic model of metabolic signalling, involving glucagon-regulated metabolism of multiple nutrients by the liver and other tissues, including amino acids and lipids, providing reciprocal feedback to regulate glucagon secretion and even alpha cell mass. Here we describe how various nutrients are sensed, transported and metabolised in alpha cells, providing an integrative model for the metabolic regulation of glucagon secretion and action. Importantly, we discuss where these nutrient-sensing pathways intersect to regulate alpha cell function and highlight key areas for future research.

AB - Since the discovery of glucagon 100 years ago, the hormone and the pancreatic islet alpha cells that produce it have remained enigmatic relative to insulin-producing beta cells. Canonically, alpha cells have been described in the context of glucagon's role in glucose metabolism in liver, with glucose as the primary nutrient signal regulating alpha cell function. However, current data reveal a more holistic model of metabolic signalling, involving glucagon-regulated metabolism of multiple nutrients by the liver and other tissues, including amino acids and lipids, providing reciprocal feedback to regulate glucagon secretion and even alpha cell mass. Here we describe how various nutrients are sensed, transported and metabolised in alpha cells, providing an integrative model for the metabolic regulation of glucagon secretion and action. Importantly, we discuss where these nutrient-sensing pathways intersect to regulate alpha cell function and highlight key areas for future research.

KW - amino acids

KW - endocrine pancreas

KW - fatty acids

KW - glucose metabolism

KW - TCA cycle

U2 - 10.1530/JOE-23-0081

DO - 10.1530/JOE-23-0081

M3 - Journal article

C2 - 37523232

AN - SCOPUS:85170295107

VL - 259

JO - Journal of Endocrinology

JF - Journal of Endocrinology

SN - 0022-0795

IS - 1

M1 - e230081

ER -