In order to investigate secretion of extrapancreatic glucagon in dogs, plasma glucagon and total immunoreactive glucagon (IRG) in response to arginine were determined with antisera specific and non-specific for pancreatic glucagon, respectively. Only a tiny rise of plasma glucagon was observed in the portal vein following arginine infusion performed immediately after total pancreatectomy in a g...

The hormone glucagon has long been dismissed as a minor contributor to metabolic disease. Here we propose that glucagon excess, rather than insulin deficiency, is the sine qua non of diabetes. We base this on the following evidence: (a) glucagon increases hepatic glucose and ketone production, catabolic features present in insulin deficiency; (b) hyperglucagonemia is present in every form of po...

To determine unambiguously if suppression of glucagon action will eliminate manifestations of diabetes, we expressed glucagon receptors in livers of glucagon receptor-null (GcgR(-/-)) mice before and after β-cell destruction by high-dose streptozotocin. Wild type (WT) mice developed fatal diabetic ketoacidosis after streptozotocin, whereas GcgR(-/-) mice with similar β-cell destruction remained...

A new report in this issue of Diabetes provides evidence that at least some metabolic actions of glucagon may be mediated by fibroblast growth factor 21 (FGF21). Habegger et al. (1) report that native glucagon raises plasma FGF21 levels in human subjects, confirming the report by Arafat et al. (2). They also find that a synthetic glucagon receptor agonist (IUB288) upregulates FGF21 expression i...

We report sensitive radioimmunoassay procedures for glucagon-like immunoreactivity and for pancreatic glucagon, with use of antisera generated in rabbits by the injection of glucagon covalently coupled to thyroglobulin. Optimum assay conditions were determined. These assays have absolute limits of sensitivity of 10 to 20 pg, an intra-assay coefficient of variation of 8%, and an inter-assay coef...

Food intake in chickens is regulated in a manner similar to that in mammals. Corticotropin-releasing factor (CRF), which increases the plasma corticosterone concentration, plays an important role as a mediator of many appetite-suppressive peptides in the central nervous system in both species. Central administration of glucagon suppresses food intake in rats. However, the anorexigenic action of...

This study evaluated the chronotropic and inotropic responses to glucagon in spontaneously beating isolated right atria of rat heart. For comparison, we also investigated the effects resulting from stimulating β-adrenoceptors with isoproterenol in this tissue. Isoproterenol increased both atrial frequency and contractility but glucagon only enhanced atrial rate. The transcript levels of glucago...

Recent reports" have described successful production of pancreatic glucagon-specific antisera with the C-terminal tryptic fragment of porcine glucagon, glucagon (19-29), as immunogen. One of the antisera, OAL-123, was efficiently used for development of a radioimmunoassay as a tool for measuring pancreatic glucagon in biologic fluids and tissue extracts2),4). Trypsin-catalyzed digestion of porc...

Genetic disruption or pharmacologic inhibition of glucagon signaling effectively lowers blood glucose but results in compensatory glucagon hypersecretion involving expansion of pancreatic α-cell mass. Ben-Zvi et al. recently reported that angiopoietin-like protein 4 (Angptl4) links glucagon receptor inhibition to hyperglucagonemia and α-cell proliferation [Ben-Zvi et al. (2015) Proc Natl Acad S...

Glucagon, secreted from islet -cells, mobilizes liver glucose. During hyperglycemia, glucagon secretion is inhibited by paracrine factors from other islet cells, but in type 1 and type 2 diabetic patients, this suppression is lost. We investigated the effects of -cell secretory products zinc and insulin on isolated rat -cells, intact islets, and perfused pancreata. Islet glucagon secretion was ...