Disease relevance of Gcg

• They also have chronic fasting hypoglycemia and a reduced rise in blood glucose levels during an intraperitoneal glucose tolerance test, which is consistent with a deficiency of circulating glucagon [1].
• To define the contribution of mature glucagon deficiency to the hypoglycemia and alpha-cell hyperplasia, we have attempted to correct the defects by delivery of exogenous glucagon by micro-osmotic pumps [2].
• Elimination of glucagon-like peptide 1R signaling does not modify weight gain and islet adaptation in mice with combined disruption of leptin and GLP-1 action [3].
• Body weight, food intake and circulating glucagon were unchanged [4].
• Glucagon-like peptide-1 (GLP-1) reduces insulin requirement in diabetes mellitus and promotes satiety [5].
• We have demonstrated that in response to a HFD, brain GLP-1 signaling induces hyperinsulinemia and insulin resistance and decreases energy expenditure by reducing metabolic thermogenesis and ambulatory activity [6].

Psychiatry related information on Gcg

• ABSTRACT : We studied the regulation of brain acetyl CoA carboxylase (ACC) activity during food deprivation and under the influence of hormones of glucose homeostasis: glucagon and insulin [7].
• Behavioral studies have shown that glucagon diminished spontaneous locomotor activity in rats and mice, impaired exploratory activity and reduced amphetamine-induced hyperactivity [8].

High impact information on Gcg

• Here we show that mice deficient in Hes1 (encoding Hes-1) display severe pancreatic hypoplasia caused by depletion of pancreatic epithelial precursors due to accelerated differentiation of post-mitotic endocrine cells expressing glucagon [9].
• The endodermal epithelium of vertebrates generates many types of enteroendocrine cells, including the insulin- and glucagon-secreting cells of the islets of Langerhans [10].
• Here we show that homozygous, but not heterozygous, mice deficient in Glut-2 are hyperglycaemic and relatively hypo-insulinaemic and have elevated plasma levels of glucagon, free fatty acids and beta-hydroxybutyrate [11].
• Maintenance of blood glucose by the liver is normally initiated by extracellular regulatory molecules such as glucagon and vasopressin triggering specific hepatocyte receptors to activate the cAMP or phosphoinositide signal transduction pathways, respectively [12].
• The diabetes was progressive and characterized by elevated blood glucose and glucagon that coincided with reduced serum and pancreatic insulin [13].

Chemical compound and disease context of Gcg

• No single treatment reversed the hyperglycemia or elevated hormone production of obese mice, although slightly lower values of glucose, insulin, glucagon and corticosterone were associated with pair-feeding [14].
• Furthermore, capsaicin-sensitive sensory nerve fibers are partially involved in 2-DG-induced glucagon secretion and hyperglycemia, whereas sensory nerves are not involved in 2-DG-induced insulin secretion [15].
• These results suggest that, in mice, BRL 26830A may promote insulin secretion mainly via beta 3 receptors and partially via beta 2 receptors on pancreatic-islet B cells, and that glucagon may be secreted as the result of hypoglycemia induced by this agent [16].
• Furthermore, glucagon failed to elicit an increase in the concentration of cyclic AMP in spontaneously beating hearts that developed tachycardia [17].
• In STZ-induced (65 mg/kg) diabetic rats, MDL 29311 attenuated the increase in plasma nonesterified fatty acids during an 18-h fast; had little or no effect on glucagon, pyruvate, lactate, beta-hydroxybutyrate, acetoacetate, or cholesterol; and did not induce hypoglycemia in rats fasted up to 64 h [18].

Biological context of Gcg

• To examine the role of glucagon in glucose homeostasis, mice were generated with a null mutation of the glucagon receptor (Gcgr(-/-)) [19].
• Furthermore, the lean phenotype of Gcgr(-/-) mice suggests glucagon action may be involved in the regulation of whole body composition [19].
• These results demonstrate that the lack of mature glucagon in PC2(-/-) mice is responsible for the aberrant blood glucose levels, islet morphology, and gene expression, and they confirm the role of glucagon as a tonic insulin antagonist in regulating glycemia [2].
• Glucagon-like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion and inhibits food intake, gastric emptying, and glucagon secretion, actions that promote reduction of fasting and postprandial glycemia in subjects with type 2 diabetes [20].
• Glucagon stimulated cAMP generation and exocytosis dose dependently with an EC50 of 1.6-1.7 nm [21].

Anatomical context of Gcg

• Glucagon, the counter-regulatory hormone to insulin, is secreted from pancreatic alpha cells in response to low blood glucose [19].
• These data indicate that glucagon is essential for maintenance of normal glycemia and postnatal regulation of islet and alpha and delta cell numbers [19].
• Many of these cells contain both glucagon and PP which, by immunogold labelling of consecutive thin sections, can be shown to co-exist within individual secretory granules [22].
• Glucagon-like peptide-1 enhances production of insulin in insulin-producing cells derived from mouse embryonic stem cells [23].
• Activin B was first detected at E12.5 in epithelial cells coexpressing glucagon [24].

Associations of Gcg with chemical compounds

• PMA (4-phorbol 12-myristate 13-acetate) but not glucagon, glucose-dependent insulinotropic polypeptide (GIP), or epinephrine produced heterologous desensitization in vitro [20].
• Chelation of intracellular calcium (intracellular [Ca(2+)]) reduced glucagon-mediated ERK1/2 activation [25].
• In conclusion: carbachol is a potent stimulator of glucagon secretion [26].
• Insulin secretion induced by IPNA was increased by glucagon and inhibited by somatostatin [27].
• Influences of gastro-intestinal polypeptides and glucose on glucagon secretion induced by cholinergic stimulation [26].
• We show that adenovirus-mediated expression of PC1/3 in alpha cells increases islet GLP-1 secretion, resulting in improved glucose-stimulated insulin secretion and enhanced survival in response to cytokine treatment [28].

Physical interactions of Gcg

• In this report, we show that Pax6 additionally binds the glucagon gene promoter G1-element and forms a transcriptionally active complex with another homeodomain protein, Cdx2/3 [29].
• Pax6 and Cdx2/3 form a functional complex on the rat glucagon gene promoter G1-element [29].
• Adenylate cyclase activity and [125I]iodoglucagon binding were measured in the plasma membrane preparations over a wide range of glucagon concentrations [30].

Co-localisations of Gcg

• Expression of NK-1 R co-localized with expression of glucagon [31].

Regulatory relationships of Gcg

• We show herein that ngn3-positive cells coexpress neither insulin nor glucagon, suggesting that ngn3 marks early precursors of pancreatic endocrine cells [32].
• However, the absence of PC2 activity in alphaTC-DeltaPC2 leads to a complete block in the production of mature glucagon [33].
• Somatostatin and glucose both markedly inhibited carbachol-induced glucagon secretion [26].
• By E18.5 activin B was localized to forming islets where cells coexpressed glucagon and were arranged in the mantle formation characteristic of mature alpha cells [24].
• In contrast to Pdx 1-deficient mice, the early glucagon-expressing cells do not develop in Raldh2 knockout embryos [34].

Other interactions of Gcg

• 2. Cells from two different noninsulinoma tumors, when adapted to culture, began to express either insulin, glucagon, or somatostatin [35].
• Intraperitoneal delivery of 0.5 microg glucagon/h in PC2(-/-) mice resulted in the normalization of blood glucose concentrations [2].
• Neither PC1 nor PC2 processed glucagon from proglucagon in vitro [36].
• In contrast, no significant perturbation in the insulin response to perfused glucagon was detected under conditions of low (4.4 mmol/l) or high (16.6 mmol/l) glucose in GLP-1R -/- mice [37].
• The serum glucagon levels in IR-deficient and nondiabetic littermates were comparable [38].

Analytical, diagnostic and therapeutic context of Gcg

• By immunofluorescence on cytospin preparations and on semithin sections of mouse pancreatic buds, we have found glucagon and pancreatic polypeptide (PP)-containing cells at embryonal day 10.5 (E 10.5) in dorsal buds and at E 11.5 in ventral buds [22].
• Hepatectomy suppressed the response to glucagon but was without effect on the response to the other peptides [39].
• Kidney hilus ligation suppressed the responses to PACAP-38, PTH, helodermin, helospectin, VIP, glucagon and calcitonin [39].
• We observed by immunohistochemistry and confocal microscopy that beta TC-6 cells contain abundant insulin and small amounts of glucagon and somatostatin (SRIF) [40].
• Insulin, proinsulin and glucagon extracted from lean rat pancreases were studied in radioimmunoassay, radioreceptorassay and bioassay systems [41].

References