UNIPROT:P01275 - FACTA Search

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Query: UNIPROT:P01275 (glucagon)
26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High plasma concentrations of C-terminal immunoreactive glucagon (IRG) have been found during early life in several mammalian species. We have analyzed the plasma IRG of 12 h to 60 day-old dogs in terms of the 4 peaks (IRG greater than 20,000, IRG9000, IRG3500 and IRG2000) obtained by gel filtration on Bio-Gel P-30. Significant changes with age and in response to administered agents were confined to IRG9000 and IRG3500. IRG9000 was 9-fold higher in 12-36 h old dogs than in adults (108 +/- 24 pg/ml pancreatic glucagon equivalents v. 12 +/- 3 pg/ml, mean +/- SEM) and showed a decline to 2-fold higher (27 +/- 5 pg/ml) at 31-60 days. IRG3500 was higher than in the adult only during the first 36 h of life (36 +/- 5 pg/ml v. 15 +/- 3 pg/ml). Arginine infusion (0.5 g/kg over 15 min) caused an increase in plasma levels of both IRG9000 and IRG3500 in the newborn, whereas in adult dogs only IRG3500 was increased. Insulin injection (0.2 U/kg intravenously) causing a marked hypoglycemia had no significant effect on the plasma level of any IRG component in newborn dogs. Dihydrosomatostatin infusion (10 micrograms/kg bolus +/- 90 micrograms/kg over 30 min) caused a decrease in both IRG9000 and IRG3500. The increased basal level and secretory response to arginine of IRG9000 in newborn dogs may reflect an immaturity of the A cells, whereby more of this component, which may represent a precursor of pancreatic glucagon, is secreted than in the adult. The immature A cells also appear to have an impaired secretory response to hypoglycemia.
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PMID:Plasma glucagon-immunoreactive components in early life in dogs. 286 2

We assessed the effects of insulin and normalization of blood glucose on plasma levels of somatostatin-like immunoreactivity (SLI) in patients with noninsulin-dependent diabetes mellitus (NIDDM). In one series of experiments, normalization of blood glucose was achieved by Biostator-controlled feedback infusion of insulin. This procedure reduced plasma SLI levels by 34% [from 17.1 +/- 2.1 (+/- SEM) to 11.3 +/- 1.9 pg/ml; P less than 0.05], concomitant with a significant reduction in plasma glucagon and C-peptide and an evanescent decrease in plasma gastric inhibitory peptide (GIP) levels. An ensuing mixed meal elicited a rise in SLI that reached the same levels during infusion of insulin as during uncontrolled hyperglycemia; the incremental increase was, however, 45% higher (P less than 0.005) during insulin infusion. Furthermore feedback insulin infusion enhanced GIP and decreased C-peptide responses, but did not affect the glucagon response to the meal. To further evaluate the influence of insulin of SLI levels, we compared the effects of normo- and hyperglycemia during constant hyperinsulinemia by varying the rate of glucose infusion (glucose clamping). Basal SLI levels decreased significantly only during the normoglycemic clamp. The SLI response to a meal was more pronounced during the normoglycemic than the hyperglycemic clamp. The patterns of glucagon and GIP were similar during the two clamp conditions, while both basal and stimulated C-peptide levels were lower during the normoglycemic clamp. To investigate the temporal relationship between changes in blood glucose and SLI levels, patients were studied during a prolonged (270-min) period of normoglycemic clamp and fasting. After attaining normoglycemia, SLI levels continued to decline for 150 min, whereas glucagon and GIP levels did not change. We conclude that in patients with NIDDM, insulin significantly lowers basal SLI levels if normoglycemia is concomitantly attained; this action of insulin was partially dissociated from its hypoglycemic action; hyperglycemia per se inhibits a meal-induced SLI response, and insulin effects on SLI are not secondary to changes in glucagon or GIP levels.
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PMID:Effects of insulin on fasting and meal-stimulated somatostatin-like immunoreactivity in noninsulin-dependent diabetes mellitus: evidence for more than one mechanism of action. 286 96

In order to evaluate whether glucagon-induced hyperkalemia is due to mobilization of potassium from the splanchnic region, we measured potassium changes in the hepatic veins following a glucagon injection into the ascending aorta. Twenty-seven subjects undergoing routine cardiac catheterization for diagnostic purposes were studied. Hepatic venous and aortic blood samples were withdrawn simultaneously under basal condition and 30, 60, 120, 180, 300, 600 s after a bolus injection of either saline, glucagon (100 ng/kg body weight) or glucagon +somatostatin (100 micrograms). After the intra-aortic injection, plasma glucagon in the hepatic veins reached levels comparable to those observed under pathophysiological conditions. Plasma potassium increased promptly with a peak at 60 s (delta max: 0.79 +/- 0.12 mmol/l, mean +/- SEM; p less than 0.01). The glucose increment peaked at 300 s (delta max: 2.36 +/- 0.20 mmol/l, mean +/- SEM; p less than 0.01). Potassium increment was potentiated by the addition of somatostatin, despite the abolition of insulin and C-peptide rises (potassium delta max: 0.56 +/- 0.10 mmol/l; p less than 0.05). In conclusion, these data demonstrate that glucagon induces a transient mobilization of potassium from the splanchnic region in man. This effect of glucagon on potassium is not antagonized by glucagon-induced insulin secretion.
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PMID:Pathophysiological doses of glucagon cause a transient increase of the hepatic vein potassium concentration in man. 287 Apr 23

The physiological significance of the hyperglucagonemia that occurs in patients with many catabolic conditions is unclear. The effect of hyperglucagonemia on resting metabolic rate (RMR) was studied in six normal subjects. Infusion of somatostatin (SRIH; 500 micrograms/h for 210 min) resulted in a 5-fold decrease in plasma C-peptide and a 2-fold decrease in plasma insulin and glucagon concentrations, but did not change RMR significantly. When glucagon (0.2 micrograms/kg X h), was infused with SRIH (500 micrograms/h for 210 min), the decreases in plasma C-peptide and insulin were similar to that during the infusion of SRIH alone, but plasma glucagon increased from 160 +/- 24 (+/- SEM) to 560 +/- 80 pg/mL (P less than 0.001). There was a significant increase in RMR during the entire period (210 min) of glucagon infusion (P less than 0.01). During the last hour of the glucagon plus SRIH infusion, the RMR was 1.38 +/- 0.10 Cal/min, which was 15% higher than the preinfusion RMR (1.19 +/- 0.10 Cal/min; P less than 0.01) and 14% higher than the RMR during the same period when SRIH alone was infused (1.21 +/- 0.11 Cal/min; P less than 0.01). When SRIH and glucagon were infused, protein oxidation (calculated from urinary nitrogen loss) was 52 +/- 5 mg/min, 29% higher than when SRIH alone was infused (40 +/- 5 mg/min; P less than 0.05). These results indicate that hyperglucagonemia during insulin deficiency results in an increase in energy expenditure, which may contribute to the catabolic state in many conditions.
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PMID:Hyperglucagonemia increases resting metabolic rate in man during insulin deficiency. 288 43

To evaluate the glomerular filtration rate (GFR) response to a protein meal in patients with diabetes and to study the role of glucagon and growth hormone, we studied inulin clearance for three 30-minute periods before and 3 hours after an 80 g protein meal in seven healthy volunteers and 10 patients with diabetes. Patients with diabetes were chosen because their renal response to such a meal has been reported to be abnormal. All had an increase in GFR and plasma glucagon levels after the protein meal. The peak rise in GFR occurred from 1 to 2 1/2 hours after the meal (mean +/- SEM, delta 26 +/- 5 mL/min/m2, controls; delta 22 +/- 7 mL/min/m2, patients with diabetes), with the mean time to normal rise in GFR occurring at 2 hours after the meal. Similarly, plasma glucagon values peaked at different times in individual patients (delta 769 +/- 532 pg/mL, controls; delta 267 +/- 69 pg/mL, patients with diabetes), with the mean plasma glucagon rise occurring 1 hours after the meal. Premeal growth hormone levels tended to be higher in the patients with diabetes (7.6 +/- 1.4 vs 2.1 +/- 0.4 ng/mL), and did not change after the meal. To allow study of the contribution of the increased plasma glucagon to the rise in GFR, eight of these patients (five with diabetes) volunteered to undergo a second GFR response test with a simultaneous infusion of somatostatin. The glucagon response was significantly lowered at all time periods during the infusion (P less than 0.05); no significant change in growth hormone occurred. Without somatostatin in these eight patients, peak increase in postmeal GFR average 20.6 +/- 1.5 mL/min/m2; with the somatostatin, peak increase in GFR was 6.0 +/- 1.8 mL/min/m2 (P less than 0.01). Neither metabolic control nor degree of albuminuria was significantly different at the time of the two studies. Thus, as has been shown in animals, somatostatin infusion limits the rise in GFR after a protein meal in humans.
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PMID:Somatostatin limits rise in glomerular filtration rate after a protein meal. 288 74

We examined the effect of somatostatin (SRIH) infusion on insulin-mediated glucose disposal (Rd) in normal young subjects (n = 8) to determine the influence of SRIH on insulin action. Paired 3-h euglycemic insulin clamp studies were performed in random order employing insulin alone (25 mU/m2 X min) or insulin with SRIH (250 micrograms/h) and replacement of basal glucagon (0.4 ng/kg X min). Basal plasma glucose, insulin, glucagon (IRG), and GH concentrations, hepatic glucose production, and Rd were similar on each occasion. Steady state (10-180 min) plasma insulin insulin alone, 283 +/- 10 (+/- SEM); insulin, IRG, and SRIH, 284 +/- 10 pmol/L) and glucagon levels (insulin alone, 84 +/- 7; insulin, IRG, and SRIH, 82 +/- 7 ng/L) were similar. Hepatic glucose production (insulin alone, 0.66 +/- 0.12; insulin, IRG, and SRIH, 0.78 +/- 0.48 mg/kg X min) and Rd (insulin alone, 8.16 +/- 0.62; insulin, IRG, and SRIH, 8.17 +/- 0.61 mg/kg X min) were not different at steady state. We conclude that SRIH infusion with glucagon replacement does not augment insulin-mediated glucose disposal in normal young subjects at physiological insulin levels.
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PMID:Somatostatin does not alter insulin-mediated glucose disposal. 288 37

The metabolic effects and secretory properties of a radiation-induced transplantable insulinoma were examined in 16-17 week old NEDH rats. Subcutaneous subscapular implantation of tumour fragments resulted in hyperphagia, increased body weight gain, marked hyperinsulinaemia and severe hypoglycaemia, with the resulting death of the recipient by 27 days. Ultimate tumour size was 2.1 +/- 0.4 g (mean +/- SEM). At 3 days after transplantation, plasma glucose and insulin responses to intraperitoneal glucose, insulin, arginine and adrenaline were similar to control rats. At 20 days, plasma glucose concentrations of insulinoma-bearing rats remained low throughout glucose tolerance tests, and insulin responsiveness to glucose stimulation was absent. 2-Deoxy-D-glucose produced only a small rise of glucose concentrations in tumour-bearing rats. Insulin sensitivity was not appreciably impaired at 20 days despite severe hyperinsulinaemia and hypoglycaemia. The ability of adrenaline and propranolol to suppress plasma insulin and raise plasma glucose concentrations was also retained. At 20 days, glucagon evoked a marked plasma insulin response with no change in plasma glucose concentrations. In contrast, arginine and glibenclamide failed to stimulate insulin above high basal concentrations.
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PMID:Metabolic effects and secretory properties of a radiation-induced transplantable rat insulinoma. 288 53

Imprecise control of neonatal glucose homeostasis may be partially due to decreased hepatic response to insulin. In prior kinetic studies the effect of that response could not be determined because the hormonal effects of insulin could not be separated from those of glucagon. Somatostatin (SRIF) suppresses secretion of both and has been used to differentiate the hormonal effects. Eighteen term lambs (age 4.2 +/- 0.3 days and birth weight 4.0 +/- 0.2 kg (M +/- SEM] were infused with 0.9% NaCl at 0.06 mL.kg-1 min-1 plus 100 microCi/kg D[6-3H] glucose by prime plus constant infusion. Ra (production) and Rd (utilization) were measured during infusion of SRIF or SRIF plus replacement insulin (0.2 mU.kg-1 min-1). There was a rise in pl. glucose (98 +/- 10 to 119 +/- 10 mg/dL (P less than .0001)); a fall (46.2%) in pl insulin [13 +/- 2 to 7 +/- 1 microU/mL (P less than .0004); a rise in Ra (7.8 +/- 1.5 to 13.2 +/- 4.1 mg.kg-1 min-1 P less than .047); and a rise in Rd (7.7 +/- 1.4 to 11.3 +/- 3.0 mg.kg-1 min-1 (P less than .047)) in SRIF treated animals compared to nontreated controls. There was no change in plasma glucagon (454 +/- 182 to 255 +/- 141 pg/mL) in SRIF treated animals compared to nontreated controls. All perturbations were eliminated when SRIF plus replacement insulin produced control insulin levels. Insulin suppression in the neonatal period resulted in glucagon being unopposed which produced an elevated rate of glucose production and elevated plasma glucose concentration.
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PMID:Hepatic response to insulin in control of glucose kinetics in the neonatal lamb. 289 78

In order to investigate the action of somatostatin-28 (SS-28) on the metabolic homeostasis of insulin-dependent diabetics, we compared its effects to those of somatostatin-14 (SS-14) in terms of insulin sparing, changes in dextrose demands, glucose fluctuations and behavior of growth hormone and glucagon secretion. Eight insulin-dependent subjects were connected to Artificial Endocrine Pancreas (Biostator) for 84 hours during which they received intravenous infusions of either SS-14, SS-28 or isotonic saline in a randomized order, after a steady state of metabolism had been achieved. Five of the patients received SS-28 100 micrograms/h and SS-14 250 micrograms/h for 10 hours and three of them SS-28, 50 micrograms/h and SS-14 250 micrograms/h for 12 hours. Identical doses of both peptides were administered as bolus infusions prior to the continuous ones. Under SS-28 100 micrograms/h and SS-14 250 micrograms/h patients required 13.5 +/- 2.3 and 14.5 +/- 1.9 U of insulin respectively vs 40 +/- 5.6 U under isotonic saline infusion (mean +/- SEM, P less than 0.005 and P less than 0.01). At the same period the apparatus delivered 15 times more dextrose under SS-28 and 20 times more under SS-14. The magnitude of glucose fluctuations diminished from 64.6 +/- 2.47 mg% without to 41.4 +/- 2 mg% under SS-14 (P less than 0.01) and 46 +/- 3.8 mg% under SS-28 (P less than 0.02). Similar changes were observed in the remaining three patients who received SS-28 in the dose of 50 micrograms/h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The antidiabetic action of somatostatin-28 as assessed by the artificial endocrine pancreas: greater potency than somatostatin-14. 289 70

On the basis of the inhibitory actions of the somatostatin analogue SMS 201-995 on growth hormone (GH) and glucagon (IRG) secretion we investigated its effects on carbohydrate metabolism of insulin-dependent diabetics. Six patients with no residual insulin secretion were connected to the artificial endocrine pancreas (AEP) and after the establishment of a steady state overnight they were injected either normal saline or 50 micrograms of SMS 201-995 s.c., t.i.d., or 100 micrograms of the same compound b.i.d. Insulin requirements were assessed by the AEP and compared during the 24 h and after the main meals. The inhibition of GH and IRG secretion was evaluated as well. 50 micrograms of SMS analogue t.i.d. induced a significant reduction of insulin requirement (mean +/- SEM) while no significant difference was observed between control and 100 micrograms s.c., b.i.d., nor between 50 micrograms and 100 micrograms. The curve of glucose fluctuations was smoother after 50 micrograms than after 100 micrograms and control. Postprandial IRG secretion was inhibited by both regimens of SMS after lunch and dinner. GH secretion was significantly inhibited after all meals during the days of analogue administration. SMS 201-995 analogue appears to have a remarkable antidiabetic activity as shown by the sparing of administered amount of insulin, suppression of counter-insulin hormones and smoothing of blood glucose curve. It may constitute a safe and effective adjunctive measure in the management of insulin-dependent diabetics.
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PMID:The effects of the somatostatin analogue SMS 201-995 on carbohydrate homeostasis of insulin-dependent diabetics as assessed by the artificial endocrine pancreas. 290 29

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