Glucagon maintains glucose homeostasis during the fasting state by promoting hepatic gluconeogenesis and glycogenolysis. Hyperglucagonemia and/or an elevated glucagon-to-insulin ratio have been reported in diabetic patients and animals. Antagonizing the glucagon receptor is expected to result in reduced hepatic glucose overproduction, leading to overall glycemic control. Here we report the disc...

Glucagon is known for its insulin-antagonist effect in the blood glucose homeostasis, while it also reduces vascular resistance. The mechanism of the vasoactive effect of glucagon has not been studied before; thereby we aimed to investigate the mediators involved in the vasodilatation induced by glucagon. The vasoactive effect of glucagon, insulin, and glucagon-like peptide-1 was studied on iso...

Hyperglucagonemia is implicated in the pathophysiology of hyperglycemia. Antagonism of the glucagon receptor (GCGR) thus represents a potential approach to diabetes treatment. Herein we report the characterization of GRA1, a novel small-molecule GCGR antagonist that blocks glucagon binding to the human GCGR (hGCGR) and antagonizes glucagon-induced intracellular accumulation of cAMP with nanomol...

Glucagon-expressing retinal amacrine cells have been implicated in regulating postnatal ocular growth. Furthermore, experimentally accelerated rates of ocular growth increase the number of neurons added to the peripheral edge of the retina. Accordingly, we assayed whether glucagon-expressing neurons within the retina regulate the proliferation of progenitors in the circumferential marginal zone...

During treatment of primary cultured hepatocytes with either glucagon or isoproterenol for several hours, the stimulations of cAMP formation by these hormones decreased time dependently. Glucagon treatment also reduced the response to isoproterenol, but isoproterenol treatment did not decrease the response to glucagon. Treatment with isoproterenol caused more rapid desensitization than treatmen...

-Aminobutyric acid (GABA) has been proposed to function as a paracrine signaling molecule in islets of Langerhans. We have shown that rat -cells release GABA by Ca -dependent exocytosis of synaptic-like microvesicles. Here we demonstrate that GABA thus released can diffuse over sufficient distances within the islet interstitium to activate GABAA receptors in neighboring cells. Confocal immunocy...

the aim of the present study was to investigate whether and by which mechanism; histamine can induce state-dependent retrieval of passive avoidance task. the pre-training or pre-test intracerebroventricular (i.c.v.) injection of histamine (20µg/mouse) impaired retrieval, when it was tested 24 h later. in the animals, which retrieval was impaired due to histamine pre-training administration, pre...

background and objective: host genetic factors such as cytokine gene polymorphisms as well as helicobacter pylori (h. pylori) infection have been found to be associated with gastric cancer risk . interleukin 1 is a pro-inflammatory cytokine involved in h. pylori-induced gastric inflammation. therefore, we analyzed the association between il-1β and il-1-rn polymorphisms and gastric cancer in per...

Exogenously administered somatostatin (SST) inhibits secretion of insulin and glucagon. Furthermore, it is hypothesized that islet SST regulates glucagon secretion by a local action. A number of studies utilizing SST antibodies have been performed to test this hypothesis, and their results have been conflicting. Five subtypes of SST receptor (SSTR1-5) mediate the effect of SST on target cells. ...

It has been suggested that the gut hormone cholecystokinin (CCK), by modulating insulin output from pancreatic beta-cells, plays an important role in the enteroinsular axis. To investigate this hypothesis, eight rats were studied on two different occasions: after injection of L 364718, a specific antagonist of CCK binding to its membrane receptor, and after vehicle injection. In both studies a ...