Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma membranes were prepared from homogenates of two well differentiated hepatomas (Morris rat 7787 and Dalton mouse 9815), two poorly differentiated hepatomas (Morris rat 7288-C and Dalton mouse 129), and normal liver. Adenylate cyclase activity and [125I]iodoglucagon binding were measured in the plasma membrane preparations over a wide range of glucagon concentrations. Nether glucagon-stimulated adenylate cyclase activity nor [125I]iodoglucagon binding could be detected in the poorly differentiated hepatomas. Fluoride and epinephrine stimulated adenylate cyclase activity in all hepatomas. Maximum activity of glucagon-stimulated adenylate cyclase and maximum binding of glucagon in the wall differentiated hepatomas were less than those of normal liver. Plasma membranes from liver and hepatomas were solubilized with Lubrol-PX and, after reducing the concentration of detergent, were incubated with [125I]iodoglucagon and then chromatographed on a column of Bio-Gel A 1,5 m. Two peaks containing both protein and [125I]iodoglucagon were found for normal liver but not for the poorly differentiated hepatomas. Fractions from the Bio-Gel column containing the greatest concentration of protein were also subjected to a binding microassay. Material from the poorly differentiated tumors did not bind glucagon in this system, whereas the solubilized normal liver membranes bound up to 1.4 pmol [125I]iodoglucagon/mg protein. This indicates that there is no detectable glucagon receptor in these undifferentiated tumors.
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PMID:Membrane receptor function and the loss of glucagon-stimulated adenylate cyclase activity in hepatomas. 21 18

Epinephrine's effect to increase metabolic rate is accompanied by changes in the plasma concentrations of insulin, glucagon, and metabolic substrates. Because both glucagon and insulin have been reported to affect thermogenesis, these hormones might contribute to or modify the thermogenic response to epinephrine. To determine if the epinephrine-induced increase in metabolic rate is secondary to changes in glucagon or insulin or to changes in the fuels modulated by these hormones, metabolic rate was measured by indirect calorimetry in five normal weight post-absorptive young men on three occasions: study A, an intravenous epinephrine infusion alone; study B, a 4-h "islet clamp" consisting of somatostatin infusion with basal insulin and glucagon replacement; and study C, an intravenous epinephrine infusion combined with the islet clamp. A 1-h base-line period preceded 2 h of epinephrine infusion. During the 4-h islet clamp (study B), metabolic rate and plasma concentrations of epinephrine, insulin, glucagon, and glucose remained unchanged. During the infusion of epinephrine alone (study A), metabolic rate and concentrations of glucagon, free fatty acids, and C-peptide increased as expected. Also as expected, the glycemic response to epinephrine infusion was much larger when insulin and glucagon levels were fixed with the islet clamp (study C). In contrast, the metabolic rate and the free fatty acid concentration responded similarly to epinephrine infusion when insulin and glucagon were fixed (study C) and when they were changing (study A). We conclude that epinephrine increases metabolic rate independently of physiological changes in plasma glucagon or insulin or the circulating fuels they modulate.
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PMID:Epinephrine's effect on metabolic rate is independent of changes in plasma insulin or glucagon. 256 29

The sphincter of Oddi is the smooth muscle connection between the bile duct and the duodenum. Its physiological function is associated with a regular motility characterized by phasic contractions superimposed on the sphincter of Oddi baseline pressure. Recently introduced ERCP-manometry permits further studies of sphincter of Oddi pharmacology. A number of drugs have so far been studied. Sedatives of the diazepam type had no effect on the sphincter, while butylscopolaminium bromide, a typical neurotropic agent, brings about cessation of the sphincter motility for 3-8 minutes. Hymecromon lowered the sphincter baseline pressure from 9.8 to 7.8 mmHg. A 1.2 mg sublingual dose of nitroglycerin, a typical musculotropic agent, caused significant relaxation of the sphincter, and decreased baseline pressure from 8.9 mmHg to 2.9 mmHg; Sphincter motility was not affected. Morphine-like analgetics, in particular pentazocine, elevated sphincter baseline pressure, but buprenorphine and tramadol did not. Pharmacological doses of gastrointestinal hormones also affect the sphincter; CCK octapeptide, glucagon and secretin are able to decrease sphincter of Oddi baseline pressure, and CCK octapeptide abolishes sphincter motility. Sphincter of Oddi pharmacology is of clinical interest. The administration of sphincter-relaxing agents, in particular nitroglycerin and butylscopolaminium bromide, enables the endoscopist to extract small common bile duct stones without previous papillotomy. Analgetics that induce sphincter contraction and thus hinder the flow of bile and pancreatic juice, may be helpful for the treatment of pain in patients with pancreatico-biliary disease. Investigations into the effect of CCK on the healthy and diseased sphincter permit us to identify patients with sphincter dysfunction using a special CCK-provocation test.
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PMID:Pharmacology of the sphincter of Oddi. 304 55

The effects of glucagon and the glucagon-(1-21)-peptide on the duodenal pressure activity in 12 healthy subjects were studied and compared with those of placebo. A 1-mg bolus injection of either glucagon or glucagon-(1-21)-peptide was given at the end of the first interdigestive migrating complex, followed by intravenous infusion of 2 mg of each drug during the subsequent 2 h. Both glucagon and glucagon-(1-21)-peptide caused significant change (p less than 0.05) in the duodenal pressure activity, as the length of the cycle was significantly increased and the migrating motor complexes were significantly reduced. The frequency of side effects and the degree of discomfort during the recordings were significantly higher (p less than 0.01) in the glucagon period than in both the glucagon-(1-21)-peptide and the placebo periods. No differences in side effects and discomfort between glucagon-(1-21)-peptide and placebo were detected. Glucagon caused a significant increase in both serum glucose and insulin levels (p less than 0.01).
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PMID:The effect of glucagon, glucagon-(1-21)-peptide, and placebo on duodenal pressure activity in healthy subjects. 352 57

Glucose tolerance tends to decrease in healthy aged subjects without family history of diabetes. Either reduced insulin secretion or insulin resistance may be responsible. Insulin secretion and insulin sensitivity were studied in 7 aged subjects (68-75 years) and 8 young controls (21-27 years). A 1-mg i.v. glucagon and a 5-U/m2 body area i.v. insulin test were run in each subject at 07(00) and at 19(00) on two different days to detect diurnal variations. An arginine test was also performed to evaluate pancreatic glucagon behavior. In the evening, young subjects presented a glucose tolerance impairment with significantly decreased plasma insulin levels, and a reduced hypoglycemic effect of exogenous insulin. Resistance to both endogenous and exogenous insulin in the aged was observed in the morning without significant morning/evening variations. Since the response to contra-insular hormones (GH in the insulin test, glucagon in the arginine test) was the same in both age groups, their role in the phenomenon could be ruled out. It is suggested that in the aged a stable reduction in number and/or a change in affinity of insulin receptors may occur. In addition, since aging is seen to be associated with the disappearance of diurnal variations in glucose tolerance and insulin secretion and sensitivity, and since a reduction in the receptor level of young healthy subjects in the evening has been reported by some authors, it is suggested that aged subjects may be less able to modulate the binding of insulin to its peripheral receptors in the course of the day.
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PMID:Diurnal variations in insulin secretion and insulin sensitivity in aged subjects. 700 42

In vitro, truncated glucagon-like peptides [GLP-1(7-36)-amide and GLP-1(7-37)] increase insulin secretion in a glucose-dependent manner, and desensitization to the action of GLP-1(7-37) has been demonstrated acutely with high concentrations. The purpose of these studies was to evaluate the glucose dependency and threshold of GLP-1(7-37) action in normal rats and in a rat model of type II diabetes and to assess the effects of long-term administration in vivo. All studies were conducted in conscious catheterized rats. An intravenous (IV) infusion of GLP-1(7-37) at 0.5, 5, or 50 pmol/min/kg during the second hour of a 2-hour 11-mmol/L hyperglycemic clamp in Sprague-Dawley rats produced a dose-related enhancement of the glucose-induced increase in plasma insulin concentration. A 1-hour infusion of a submaximal dose of GLP-1(7-37) (5 pmol/min/kg IV) in fasted and fed Sprague-Dawley rats produced small transient increases in plasma insulin (incremental increases above basal, 72 +/- 27 and 96 +/- 28 pmol/L, respectively) and decreases in plasma glucose (to levels > or = 5.2 mmol/L). Infusion of GLP-1(7-37) (5 pmol/min/kg IV) during a hyperglycemic clamp at two sequentially increasing concentrations of glucose, 11 and 17 mmol/L, produced incremental increases in insulin of 600 and 1,200 pmol/L, respectively, relative to levels in clamped control rats. Similarly, infusion of GLP-1(7-37) (5 pmol/min/kg IV) in hyperinsulinemic, hyperglycemic Zucker diabetic fatty (ZDF) rats produced a transitory increase in plasma insulin concentration and normalized the plasma glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose-dependent action of glucagon-like peptide-1 (7-37) in vivo during short- or long-term administration. 766

Glucagon-like peptide-2 (GLP-2) regulates energy homeostasis via effects on nutrient absorption and maintenance of gut mucosal epithelial integrity. The biological actions of GLP-2 in the central nervous system (CNS) remain poorly understood. We studied the sites of endogenous GLP-2 receptor (GLP-2R) expression, the localization of transgenic LacZ expression under the control of the mouse GLP-2R promoter, and the actions of GLP-2 in the murine CNS. GLP-2R expression was detected in multiple extrahypothalamic regions of the mouse and rat CNS, including cell groups in the cerebellum, medulla, amygdala, hippocampus, dentate gyrus, pons, cerebral cortex, and pituitary. A 1.5-kilobase fragment of the mouse GLP-2R promoter directed LacZ expression to the gastrointestinal tract and CNS regions in the mouse that exhibited endogenous GLP-2R expression, including the cerebellum, amygdala, hippocampus, and dentate gyrus. Intracerebroventricular injection of GLP-2 significantly inhibited food intake during dark-phase feeding in wild-type mice. Disruption of glucagon-like peptide-1 receptor (GLP-1R) signaling with the antagonist exendin-(9-39) in wild-type mice or genetically in GLP-1R(-)/- mice significantly potentiated the anorectic actions of GLP-2. These findings illustrate that CNS GLP-2R expression is not restricted to hypothalamic nuclei and demonstrate that the anorectic effects of GLP-2 are transient and modulated by the presence or absence of GLP-1R signaling in vivo.
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PMID:Glucagon-like peptide (GLP)-2 action in the murine central nervous system is enhanced by elimination of GLP-1 receptor signaling. 1126 90

A possible role for GLUT2 transiently expressed in the rat jejunal brush-border membrane (BBM) under the influence of glucagon-like peptide 2 (GLP-2) was investigated using in vivo perfusion of the intestinal lumen as well as isolation of membrane proteins and immunohistochemistry. A 1 h vascular infusion of GLP-2 in vivo doubled the rate of fructose absorption and this increase could be blocked by luminal phloretin. Immunohistochemistry of frozen sections of rat jejunum showed the expression of GLUT2 in both the basolateral and BBMs of mature enterocytes. Perfusion of the intestinal lumen with 50 mM D-glucose or vascular infusion of 800 pM GLP-2 for 1 h increased the expression of GLUT2 in the BBM. Quantification of these changes using Western blotting of biotinylated surface-exposed protein showed a doubling of the expression of GLUT2 in the BBM, but the effects of glucose and GLP-2 were not additive. These results indicate that vascular GLP-2 can promote the insertion of GLUT2 into the rat jejunal BBM providing a low-affinity/high-capacity route of entry for dietary hexoses.
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PMID:Rapid insertion of GLUT2 into the rat jejunal brush-border membrane promoted by glucagon-like peptide 2. 1209 16

Abdominally obese individuals have reduced 24-h plasma GH concentrations. Their normal plasma IGF-I levels may reflect GH hypersensitivity. Alternatively, obesity-associated hyposomatotropism may cause less biological effect in target tissues. We therefore determined whole-body responsiveness to the anabolic effects of GH in abdominally obese (OB) and normal weight (NW) premenopausal women. A 1-h iv infusion of GH or placebo was randomly administered to six NW (body mass index, 21.1 +/- 1.9 kg/m(2)) and six OB (body mass index, 35.5 +/- 1.5 kg/m(2)) women in a cross-over design. Endogenous insulin, glucagon and GH secretion was suppressed by infusion of somatostatin. Whole-body protein turnover was measured using a 10-h infusion of [(13)C]-leucine. GH administration induced a similar plasma GH peak in NW and OB women (49.8 +/- 10.4 vs. 45.1 +/- 5.6 mU/liter). GH, compared with placebo infusion, increased nonoxidative leucine disposal, P < 0.0001) and endogenous leucine appearance (R(a), P = 0.0004) but decreased leucine oxidation (P = 0.0051). All changes were similar in both groups. Accordingly, whole-body GH responsiveness, defined as the maximum response of nonoxidative leucine disposal, leucine R(a), and oxidation per unit of GH, was not different in OB and NW women (0.25 +/- 0.18 vs. 0.19 +/- 0.17 micro mol/kg.h, 0.21 +/- 0.23 vs. 0.13 +/- 0.17 micro mol/kg.h, and -0.10 +/- 0.08 vs. -0.08 +/- 0.05 micro mol/kg.h, respectively). These results indicated that whole-body tissue responsiveness to the net anabolic effect of GH is similar in OB and NW women. Hence, we inferred that hyposomatotropism may promote amino acid oxidation and blunt protein turnover in abdominal obesity. However, hyposomatotropism cannot account for all anomalous features of protein metabolism in abdominally obese humans.
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PMID:Growth hormone blunts protein oxidation and promotes protein turnover to a similar extent in abdominally obese and normal-weight women. 1246 70

It has been suggested that (abdominally) obese individuals are hypersensitive to growth hormone (GH) action. Because GH affects glucose metabolism, this may impact glucose homeostasis in abdominal obesity. Therefore, we studied the effect of GH on glucose metabolism in abdominally obese (OB) and normal-weight (NW) premenopausal women. A 1-h intravenous infusion of GH or placebo was randomly administered to six NW [body mass index (BMI) 21.1 +/- 1.9 kg/m(2)] and six OB (BMI 35.5 +/- 1.5 kg/m(2)) women in a crossover design. Insulin, glucagon, and GH secretion were suppressed by concomitant infusion of somatostatin. Glucose kinetics were measured using a 10-h infusion of [6,6-(2)H(2)]glucose. In both groups, similar physiological GH peaks were reached by infusion of GH. GH strongly stimulated endogenous glucose production (EGP) in both groups. The percent increase was significantly greater in OB than in NW women (29.8 +/- 11.3 vs. 13.3 +/- 7.4%, P = 0.014). Accordingly, GH responsiveness, defined as the maximum response of EGP per unit GH, was increased in OB vs. NW subjects (6.0 +/- 2.1 vs. 2.2 +/- 1.5 micromol.min(-1).mU(-1).l(-1), P = 0.006). These results suggest that the liver is hyperresponsive to GH action in abdominally obese women. The role of the somatotropic ensemble in the control of glucose homeostasis in abdominal obesity is discussed.
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PMID:Glucose homeostasis in abdominal obesity: hepatic hyperresponsiveness to growth hormone action. 1497 4


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