Disease relevance of GCG

• When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis [1].
• This suggests that the development of severe diabetic hyperglycemia requires the presence of glucagon, whether secreted by pancreatic or newly identified gastrointestinal A cells, as well as a lack of insulin [2].
• Glucagon: role in the hyperglycemia of diabetes mellitus [2].
• Despite similar hypoglycemia, sulfated insulin caused greater increment in glucagon [3].
• We propose that cellular uptake of potassium is enhanced by hyperinsulinemia in ketoacid infusion, and release of potassium results from increased glucagon levels in HCl acidosis [4].

Psychiatry related information on GCG

• The highest capacity and lowest motor activity was gained when atropine or glucagon was given in cases with detubularized pouch demonstrating an additive effect of the detubularization and drug [5].

High impact information on GCG

• Glucagon, a polypeptide hormone of 29 amino acids, is synthesized in the islets of Langerhans and immunoreactive forms of the molecule have been found in several tissues [6].
• Somatostatin perfused in canine pancreases at 10 to 20 picograms per milliliter or 10 to 20 percent of the pancreatic vein somatostatin concentration inhibited insulin and glucagon secretion [7].
• To investigate the temporal response of the liver to insulin and portal glucose delivery, somatostatin was infused into four groups of 42-h-fasted, conscious dogs (n = 6/group), basal insulin and glucagon were replaced intraportally, and hyperglycemia was created via a peripheral glucose infusion for 90 min (period 1) [8].
• Glycerol, alanine, FFA, and glucagon levels decreased proportionally to peripheral insulinemia [9].
• Exercise with or without PI was accompanied by four and fivefold increments in norepinephrine and epinephrine respectively, while glucagon (extrapancreatic) fell slightly [10].

Chemical compound and disease context of GCG

• Glucagon suppression by somatostatin reduces or abolishes hyperglycemia in dogs made insulin-deficient by somatostatin, alloxan, or total pancreatectomy [2].
• The hypoglycemia was independent of detectable changes in insulin, glucagon, epinephrine and cortisol, and was not reversed by concurrent infusion of a slight molar excess of naloxone [11].
• In normal dogs made hyperglucagonemic by phloridzin pretreatment, insulin and somatostatin suppressed glucagon at rates of 47 +/- 8 and 35 +/- 8%/h (NS), respectively, despite profound hypoglycemia [12].
• However, glucagon secretion from islets that have been autotransplanted in liver has been reported to be unresponsive to hypoglycemia yet responsive to arginine [13].
• The response to insulin-induced hypoglycemia includes increased plasma levels of glucagon, epinephrine, norepinephrine, cortisol, and growth hormone [14].

Biological context of GCG

• Dogs serve as an excellent model for studying glycemic control and various aspects of glucagon biology in vivo; however, the amino acid sequence of the dog glucagon receptor has not been reported [15].
• A repetitive sequence with repeat units (TACACGTA/GCG) that causes the size variation in the D-loop region was also found in both dogs and wolves [16].
• (c) Since totally depancreatized dogs had normal serum levels of IRG (originating presumably from the gastrointestinal tract), the question of essentiality of basal glucagon activity in glucose homeostasis during exercise could not be resolved by these experiments [17].
• We also examined the effect of low dose morphine on glucose kinetics independent of changes in the endocrine pancreas by the use of somatostatin plus intraportal replacement of basal insulin and glucagon [11].
• During pacing of the loop a significant (P less than 0.05-0.01) decrease in the postprandial small intestinal motility index was observed combined with a significant (P less than 0.05) increase in plasma insulin levels, whereas the postprandial increase in glucagon, somatostatin, gastrin, and glucose levels was not different from that in controls [18].

Anatomical context of GCG

• Adrenergic modulation of pancreatic A, B, and D cells alpha-Adrenergic suppression and beta-adrenergic stimulation of somatostatin secretion, alpha-adrenergic stimulation of glucagon secretion in the perfused dog pancreas [19].
• Although the tissue responsible for the different kalemic responses could not be defined with certainty, the data are compatible with an hepatic role in response to alterations in the portal vein insulin and/or glucagon levels in both acid infusion studies [4].
• Opposing actions of glucagon and insulin on splanchnic d cell function [20].
• Small intestinal motility and plasma levels of insulin, glucagon, gastrin, somatostatin, and glucose were examined during pacing of the residual jejunum or the isolated loop, respectively, compared with control experiments in the same dogs without pacing [18].
• Different mechanisms of action of vasoactive intestinal polypeptide (VIP) and glucagon on intestinal secretion [21].

Associations of GCG with chemical compounds

• Synergistic effect of portal glucose and glucagon-like peptide-1 to lower systemic glucose and stimulate counter-regulatory hormones [22].
• In contrast to the portal glucose infusions, there were no significant differences in glucose, insulin, glucagon, cortisol or lactate levels between systemic glucose infusion with or without GLP-1 [22].
• However, the resulting peripheral glycaemia was significantly lower compared to glucose infusion alone, and there were elevations in glucagon, cortisol and lactate [22].
• These changes can be explained by rises in epinephrine, glucagon, and cortisol [11].
• Arginine, at an arterial plasma concentration averaging 10 mM, elicited a rapid glucagon release [23].

Regulatory relationships of GCG

• In conclusion, glucagon induces delayed gastric emptying partially via COX-2-derived prostaglandins [24].
• Hence, glucagon stimulates both PGE2 and renin release [25].

Other interactions of GCG

• It potently inhibited insulin secretion, less potently inhibited pancreatic somatostatin release and stimulated glucagon secretion, similar to the effects of porcine galanin in the dog [26].
• RESULTS: A single injection of EM523 always induced phase III-like contractions in the intact gastric antrum and was accompanied by significant (P < 0.01) release of motilin, pancreatic polypeptide, and insulin; glucagon, gastrin, cholecystokinin, and secretin were not released by EM523 [27].
• Of the hormones tested, only insulin was strongly hepatotrophic; T3 had a minor effect, and glucagon, prolactin, angiotensin II, vasopressin, norepinephrine and estradiol were inert [28].
• Glucagon-like peptide-1-(7-36) amide and peptide YY mediate intraduodenal fat-induced inhibition of acid secretion in dogs [29].
• EGF, like glucagon, was still growth stimulatory to the PGE1-independent cells [30].

Analytical, diagnostic and therapeutic context of GCG

• Retrograde perfusion with 88 mg/dl glucose markedly increased both insulin and glucagon secretion relative to antegrade levels [31].
• Serum insulin, glucagon, and pancreatic polypeptide levels increased significantly after both limited and extended hepatectomy but not after sham laparotomy [32].
• Metabolic clearance rates and plasma half-lives for insulin, glucagon, and pancreatic polypeptide did not change over the study period [32].
• The wearable artificial endocrine pancreas, incorporating the needle-type glucose sensor, a computer calculating infusion rates of insulin, glucagon, or both, and infusion pumps, was tested in pancreatectomised dogs: the device produced perfect control of blood glucose for up to 7 days [33].
• Affinity chromatography of the glucagon-receptor complexes on columns of wheat germ lectin linked to agarose resulted in two fractions, one of which was not bound by the column and the other of which was specifically eluted by N-acetylglucosamine [34].

References