Disease relevance of Gcg

• Switching off pancreatic artery infusions of zinc chloride during hypoglycemia also improved the glucagon response (AUC: control group 817 +/- 107 and experimental group 3,445 +/- 573 pg . ml(-1) . 90 min(-1); n = 6, P < 0.01) [1].
• To evaluate the role of glucagon on its hepatocyte receptor concentrations, groups of rats were injected with a long-acting glucagon preparation (20 [G-20], 40 [G-40] or 60 [G-60] micrograms/100 g body weight) every 8 h for 4 days [2].
• We then sought to determine whether the glucagon impairment to SNS in BB D was due solely to their loss of islet sympathetic nerve terminals or whether other effects of autoimmune diabetes contributed [3].
• Localization of the rat genes encoding glucagon, glucagon receptor, and insulin receptor, candidates for diabetes mellitus susceptibility loci [4].
• Glucagon receptor levels, glucagon-stimulated and other forms of adenylyl cyclase activity, and regulatory component activity of adenylyl cyclase were determined in hepatic plasma membranes of rats administered streptozotocin without and with insulin to produce varying degrees of hyperglycemia [5].

Psychiatry related information on Gcg

• The daily rhythm in plasma glucagon concentrations in the rat is modulated by the biological clock and by feeding behavior [6].
• Intraperitoneal injections of antibodies to pancreatic glucagon at the onset of the first meal after 12 hours of food deprivation increased meal size 63 percent and meal duration 74 percent in rats [7].
• In contrast to vasopressin, glucagon did not stimulate Mn2+ influx into hepatocytes, but produced both a 3-fold enhancement of the rate of vasopressin-stimulated Mn2+ entry and the abolishment of the latency period [8].
• We now report that liver responses to alpha and beta adrenergic agonists as well as glucagon and vasopressin decrease during maternal deprivation [9].
• All three doses of glucagon produced long-lasting and dose-related increases in respiratory quotient which were unrelated to any changes in locomotor activity [10].

High impact information on Gcg

• Serum-free media containing 10-50 ng insulin, glucagon and epidermal growth factor (EGF) ml-1 stimulate adult rat hepatocyte proliferation in 10-15 day old primary liver cell cultures [11].
• The glucagon-like-peptide-1 receptor antagonist, Exendin (9-39) is also a functional antagonist of centrally applied glucagon-like-peptide-2 [12].
• The proglucagon-derived peptide, glucagon-like peptide-2, is a neurotransmitter involved in the regulation of food intake [12].
• Pharmacological and behavioral studies confirmed that glucagon-like-peptide-2 signaling is a specific transmitter inhibiting rodent feeding behavior and with potential long-term effects on body weight homeostasis [12].
• A glucagon-like-peptide-2 fiber plexus targets neurons expressing its receptor within the dorsomedial hypothalamic nucleus [12].

Chemical compound and disease context of Gcg

• In streptozotocin-induced diabetic Wistar rats, we observed that switching off intrapancreatic artery insulin infusions in vivo during hypoglycemia greatly improved glucagon secretion (area under the curve [AUC]: control group 240 +/- 261 and experimental group 4,346 +/- 1,259 pg . ml(-1) . 90 min(-1); n = 5, P < 0.02) [1].
• Glucagon, the pancreatic hormone secreted in response to hypoglycemia, is a key regulator of hepatic glucose production [13].
• Our aim was to investigate whether proinflammatory cytokine interleukin-6, a major mediator of the hepatic acute phase reaction, could contribute to this impairment by inhibiting hepatic glucose production stimulated by glucagon or isoproterenol in rat hepatocytes [14].
• The Halofenate induced state of reduced insulin:glucagon was associated with hypolipemia, postarginine hyperglycemia, and hyperketonemia,-three metabolic parameters characteristic of glucagon excess relative to insulin [15].
• Insulin and/or propranolol fail to prevent glycogen reserve exhaustion in the liver of hypothermic rats which could be due to activation of non-blocked alpha-adrenergic receptors or to the action of yet another glycogenolytic agent, e.g. glucagon, during hypothermia [16].

Biological context of Gcg

• Insulin and phorbol esters inhibit basal PEPCK transcription and antagonize the induction of PEPCK gene expression by glucocorticoids and glucagon (or its second messenger cAMP) [17].
• Metabolic effects of the glucagon-like peptide-1 analog liraglutide and the dipeptidyl peptidase-IV inhibitor vildagliptin were compared in rats made obese by supplementary candy feeding [18].
• Glucagon is a pancreatic hormone of 29 amino acids that regulates carbohydrate metabolism and glicentin is an intestinal peptide of 69 amino acids that contains the sequence of glucagon flanked by peptide extensions at the amino and carboxy termini [19].
• We propose that the reported inhibitory action of GLP-I on glucagon secretion is accounted for by a paracrine mechanism (e.g., mediated by stimulated release of somatostatin that in turn suppresses exocytosis in the alpha-cell) [20].
• Recently, we determined the nucleotide sequence of a mRNA of 1300 nucleotides that encodes rat pre-proglucagon, a polyprotein precursor of glucagon [21].

Anatomical context of Gcg

• These findings provide evidence supporting the molecular mechanisms of glucagon-induced hepatocyte bile secretion [22].
• Glucagon induces the plasma membrane insertion of functional aquaporin-8 water channels in isolated rat hepatocytes [22].
• It is still unclear whether locally released glucagon amplifies the secretory responsiveness of neighboring beta-cells in the intact pancreas [23].
• Assessment of the role of interstitial glucagon in the acute glucose secretory responsiveness of in situ pancreatic beta-cells [23].
• Glucagon and glucagon-like peptide-1 (GLP-1) are important regulators of glucose homeostasis, and both are involved in regulating pancreatic islet hormone secretion [24].

Associations of Gcg with chemical compounds

• MAP kinase activation was also attenuated by forskolin and glucagon, which increase intracellular cAMP, and by dibutyryl-cAMP, 8-bromo-cAMP, and 8-(4-chlorophenylthio)-cAMP [25].
• Glucagon also significantly increased hepatocyte membrane water permeability by about 70%, which was inhibited by the water channel blocker dimethyl sulfoxide (DMSO) [22].
• In fed rats, glucagon is not responsible for the daily glucose rhythm [6].
• When endogenous glucagon release was enhanced by isoproterenol (100 nmol/l), no amplification was seen in the simultaneous or subsequent insulin secretory response to glucose [23].
• We have utilized both [5-15N]glutamine and [3-13C] pyruvate as metabolic tracers in order to: (i) examine the effect of pH, glucagon (GLU), or insulin on the precursor-product relationship between 15NH3, [15N]citrulline, and, thereby, [15N]urea synthesis and (ii) elucidate the mechanism(s) by which pyruvate stimulates [15N] urea synthesis [26].

Physical interactions of Gcg

• Although the exact mechanism remains unknown, there is no doubt that the liver can adapt to physiological stress through modulation of GR binding characteristics to enhance the hepatic glucose production responsiveness to glucagon [27].
• Four selected monoclonal antibodies were all of the IgG 2a subclass type kappa and bound to protein A. One monoclonal antibody (23.8B6) was shown to be directed toward the C-terminal region and another (23.6B4) toward the N-terminal to central region of the glucagon molecule [28].
• The present study now shows that the glucagon G3 transcription factor binds to DNA sequences within cis-acting elements of the rat somatostatin and rat insulin-I genes that have been defined by others as pancreatic islet-specific transcriptional enhancers [29].
• The results suggest a role of the regulatory guanyl nucleotide-binding protein in diabetes leading to an increased dose response relationship of the hepatic adenylate cyclase system to glucagon [30].
• It is suggested that phosphoenolpyruvate carboxykinase rather than amino acid transport is the key pacemaker reaction in the long-term incubation since the direction and magnitude of the response for glucocorticoid and glucagon stimulation of glucose production is the same whether alanine or lactate is used as the 3-carbon precursor [31].

Enzymatic interactions of Gcg

• Thus, the site on ATP-citrate lyase phosphorylated by the cAMP-dependent protein kinase in vitro resides on the same octapeptide as the site of glucagon-stimulated phosphorylation in intact hepatocytes [32].

Co-localisations of Gcg

• CaM kinase I co-localized with glucagon secretory granules [33].

Regulatory relationships of Gcg

• Confocal immunofluorescence microscopy in cultured hepatocytes confirmed the glucagon-induced redistribution of AQP8 from intracellular vesicles to plasma membrane [22].
• These results indicate that the expression of glucagon and GLP-1 receptor mRNA is differentially regulated in rat pancreatic islets and suggest that regulation of receptor mRNA expression may be an important mechanism for controlling the sensitivity of the islets to glucagon and GLP-1 [24].
• Pretreating of mesangial cells with U73122 or H89 significantly attenuated ERK 1/2 phosphorylation induced by glucagon [34].
• Culture of hepatocytes with glucagon for 16 hours also inhibited the stimulation by EGF of activation of ERK2 and p70(S6k) (by approximately 50%) [35].
• Glucagon and glucocorticoids stimulate PEPCK gene transcription, whereas insulin has a dominant inhibitory effect [36].

Other interactions of Gcg

• The inhibitors of protein kinase A, H-89, and PKI, as well as the microtubule blocker colchicine, prevented the glucagon effect on both AQP8 redistribution to hepatocyte surface and cell membrane water permeability [22].
• Glucagon-like peptide I and glucose-dependent insulinotropic polypeptide stimulate Ca2+-induced secretion in rat alpha-cells by a protein kinase A-mediated mechanism [20].
• These results suggest (1) an inverse relationship between circulating glucagon levels and hepatocyte glucagon receptor concentration, and (2) a direct relation between receptor number and target-cell response [2].
• By ribonuclease protection assay we have demonstrated the expression of both glucagon and GLP-1 receptor mRNA in cultured rat islets [24].
• Activation and glucagon regulation of mitogen-activated protein kinases (MAPK) by insulin and epidermal growth factor in cultured rat and human hepatocytes [37].

Analytical, diagnostic and therapeutic context of Gcg

• We then developed a radioimmunoassay using antibodies raised against the octapeptide that was specific for enteroglucagon peptides without cross-reacting with glucagon [38].
• Immunocytochemistry shows colocalization of glucagon and the two glucagon-like peptides in identical cells [19].
• This paper highlights the diversity of both GLP-1 and glucagon activity by studying the tissue distribution of glucagon and GLP-1 receptor gene expression by both Southern blot analysis of RT-PCR products and nuclease protection assays [39].
• Glucagon1-21 has been prepared by treating native glucagon with carboxypeptidase A. Purified glucagon1-21 did not contain detectable methionine (less than 0.001 residue/mol) and the activity of the compound did not change after treatment with cyanogen bromide as has been shown with native glucagon [40].
• In the current study, glucagon was purified from two GP pancreata by a series of three HPLC steps after acid-alcohol extraction and acetone precipitation [41].

References