Glucagon Receptor Signaling and Glucagon Resistance.
Hundred years after the discovery of glucagon, its biology remains enigmatic. Accurate measurement of glucagon has been essential for uncovering its pathological hypersecretion that underlies various metabolic diseases including not only diabetes and liver diseases but also cancers (glucagonomas). The suggested key role of glucagon in the development of diabetes has been termed the bihormonal hypothesis. However, studying tissue-specific knockout of the glucagon receptor has revealed that the physiological role of glucagon may extend beyond blood-glucose regulation. Decades ago, animal and human studies reported an important role of glucagon in amino acid metabolism through ureagenesis. Using modern technologies such as metabolomic profiling, knowledge about the effects of glucagon on amino acid metabolism has been expanded and the mechanisms involved further delineated. Glucagon receptor antagonists have indirectly put focus on glucagon's potential role in lipid metabolism, as individuals treated with these antagonists showed dyslipidemia and increased hepatic fat. One emerging field in glucagon biology now seems to include the concept of hepatic glucagon resistance. Here, we discuss the roles of glucagon in glucose homeostasis, amino acid metabolism, and lipid metabolism and present speculations on the molecular pathways causing and associating with postulated hepatic glucagon resistance.
['Janah|Lina|L|', 'Kjeldsen|Sasha|S|', 'Galsgaard|Katrine D|KD|', 'Winther-Sørensen|Marie|M|', 'Stojanovska|Elena|E|', 'Pedersen|Jens|J|', 'Knop|Filip K|FK|', 'Holst|Jens J|JJ|', 'Wewer Albrechtsen|Nicolai J|NJ|']
D000596:Amino Acids D000818:Animals D015415:Biomarkers D005934:Glucagon D006801:Humans D050356:Lipid Metabolism D018027:Receptors, Glucagon D015398:Signal Transduction
diabetes amino acids glucose alpha cell hyperaminoacidemia hyperglucagonemia liver–alpha cell axis