Glucagon receptor antagonism impairs and glucagon receptor agonism enhances triglycerides metabolism in mice.

Objective: Treatment with glucagon receptor antagonists (GRAs) reduces blood glucose but causes dyslipidemia and accumulation of fat in the liver. We investigated the acute and chronic effects of glucagon on lipid metabolism in mice.

Methods: Chronic effects of glucagon receptor signaling on lipid metabolism were studied using oral lipid tolerance tests (OLTTs) in overnight fasted glucagon receptor knockout (Gcgr) mice, and in C57Bl/6JRj mice treated with a glucagon receptor antibody (GCGR Ab) or a long-acting glucagon analogue (GCGA) for eight weeks.

Arginine-induced glucagon secretion and glucagon-induced enhancement of amino acid catabolism are not influenced by ambient glucose levels in mice.

Amino acids stimulate the secretion of glucagon, and glucagon receptor signaling regulates amino acid catabolism via ureagenesis, together constituting the liver-α cell axis. Impairment of the liver-α cell axis is observed in metabolic diseases such as diabetes. It is, however, unknown whether glucose affects the liver-α cell axis.

Neprilysin Inhibition Increases Glucagon Levels in Humans and Mice With Potential Effects on Amino Acid Metabolism.

Context: Inhibitors of the protease neprilysin (NEP) are used for treating heart failure, but are also linked to improvements in metabolism. NEP may cleave proglucagon-derived peptides, including the glucose and amino acid (AA)-regulating hormone glucagon. Studies investigating NEP inhibition on glucagon metabolism are warranted.

Insulin-induced membrane permeability to glucose in human muscles at rest and following exercise.

Key Points: Increased insulin action is an important component of the health benefits of exercise, but its regulation is complex and not fully elucidated. Previous studies of insulin-stimulated GLUT4 translocation to the skeletal muscle membrane found insufficient increases to explain the increases in glucose uptake. By determination of leg glucose uptake and interstitial muscle glucose concentration, insulin-induced muscle membrane permeability to glucose was calculated 4 h after one-legged knee-extensor exercise during a submaximal euglycaemic-hyperinsulinaemic clamp.