Glucagon: acute actions on hepatic metabolism

Abstract

Type 2 diabetes mellitus is the result of impaired systemic control of glucose homeostasis, in part through the dysregulation of the hormone glucagon. Glucagon acts on the liver to increase glucose production through alterations in hepatic metabolism, and reducing the elevated glucagon signalling in diabetic patients is an attractive strategy for the treatment of hyperglycaemia. Here we review the actions of the hormone in the liver, focusing on the acute alterations of metabolic pathways. This review summarises

Gs-DREADD Knock-In Mice for Tissue-Specific, Temporal Stimulation of Cyclic AMP Signaling

“…These hormones comprise a major portion of the counterregulatory response to hypoglycemia and contribute to the maintenance of blood glucose in the fasted state. Cyclic AMP-dependent protein kinase (PKA) drives glycogen breakdown by activating glycogen phosphorylase and inhibiting glycogen synthase (52). PKA also induces gluconeogenesis by the activation of CREB and the subsequent induction of genes encoding rate-limiting gluconeogenic enzymes and transcriptional coactivators (42, 53–55).…”

“…4B). Activation of the cAMP-PKA pathway in liver by glucagon results in rapid glycogen breakdown and the release of glucose into the bloodstream (44, 52, 57). Similarly to glucagon (57), CNO rapidly increased blood glucose levels, with near doubling within 30 min of injection (Fig.…”

Chronic fractalkine administration improves glucose tolerance and pancreatic endocrine function

“…One component of insulin's action to suppress postprandial hyperglycemia is to counteract the effects of glucagon (5,6). In T2DM, insulin resistance potentiates α cell glucagon secretion and hepatic glucagon action, which stimulates hepatic glucose production (7,8).…”

“…Chronic fractalkine administration improves glucose tolerance and pancreatic endocrine function Matthew Riopel, 1 Jong Bae Seo, 1,2 Gautam K. Bandyopadhyay, 1 Pingping Li, 1,3 Joshua Wollam, 1 Heekyung Chung, 1 Seung-Ryoung Jung, 2 Anne Murphy, 4 Maria Wilson, 5 Ron de Jong, 5 Sanjay Patel, 5 Deepika Balakrishna, 5 James Bilakovics, 5 Andrea Fanjul, 5 Artur Plonowski, 5 Duk-Su Koh, 2 Christopher J. Larson, 5,6 Jerrold M. Olefsky, 1 and Yun Sok Lee glucose tolerance in HFD WT mice ( Figure 1G), but not in HFD CX3CR1-KO mice ( Figure 1H), showing that these beneficial effects of FKN-Fc are CX3CR1-dependent. Interestingly, chronic FKN-Fc administration decreased fasting plasma insulin level ( Figure 1I), similarly to what has been reported in chronic GLP-1 analog-treated animals (29).…”

An overview of glucagon research

“…This series of mini-reviews summarises the contributions of leading researchers in this field presented at a symposium 'Novel data on glucagon' at the 51st EASD Annual Meeting in Stockholm in September 2015, and covers the central role of glucagon in suppressing postprandial glucose production (Abraham and Lam [20]), its role as a key factor for development of diabetes (Lee [21]) and its regulatory effect on gluconeogenesis (Miller and Birnbaum [22]). …”