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 growth hormone profiles in adolescents with Type 1 (insulin-dependent) diabetes mellitus are characterized by both increases in pulse amplitude and higher baseline concentrations. To determine which of these abnormalities adversely affect metabolic control, we studied six young adults overnight on three occasions. On each night somatostatin (50-100 micrograms.m2-1.h-1) and glucagon (1 ng.kg-1.min-1) were infused continuously and 18 mU/kg of growth hormone was given as either: three discrete pulses of 6 mU.kg-1.h-1 at 180-min intervals or a 12-h infusion (1.5 mU.kg-1.h-1) or buffer solution only on a control night. Euglycaemia was maintained by an insulin-varying clamp. Blood samples were taken every 15 min for glucose and growth hormone and every hour for intermediate metabolites and non-esterified fatty acids. Comparable normoglycaemic conditions were achieved on all three nights. Growth hormone levels achieved (mean +/- SEM) on study nights were: 32.8 +/- 2.2 mU/l (peak level during growth hormone pulses); 9.8 +/- 0.8 mU/l (continuous growth hormone) and 1.1 +/- 0.3 mU/l (control level). Pulsatile growth hormone administration led to an increase in insulin requirements (mean +/- SEM: 0.17 +/- 0.03 vs control 0.09 +/- 0.01 mU.kg-1.min-1, p less than 0.05) whereas insulin requirements following continuous growth hormone administration were unchanged. Cross-correlation confirmed an increase in insulin requirements occurring 135 min after a growth hormone pulse (r = 0.21, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contrasting metabolic effects of continuous and pulsatile growth hormone administration in young adults with type 1 (insulin-dependent) diabetes mellitus. 161 27

To determine whether specific hormonal responses were involved in the production of cryoprotectant (glucose) by liver of the freeze tolerant wood frog, Rana sylvatica, metabolically active hepatocytes were isolated in reasonable yields (mean 20.1 +/- 1.30% SEM, n = 29) by in situ liver perfusion with collagenase. Freshly isolated cells from autumn-collected frogs contained large amounts of glycogen (650 mumol glucosyl units/g packed cells) and produced glucose from this endogenous reserve at a rate of 10 mumol g-1 hr-1 at 0 degrees. Glucose output from cells was highly responsive to the addition of hormones; rates of glucose release increased 2.1-, 1.7-, and 1.7-fold with the addition of 10(-7) M bovine glucagon, 10(-7) M epinephrine, and 5 x 10(-6) M dibutyryl-cyclic AMP, respectively. Norepinephrine, 5-hydroxytryptamine, and bovine insulin were without effect at 0.1 microM/l. Hormone stimulation of glucose release was correlated with an increase in both the total activity and the percentage a of glycogen phosphorylase in hepatocytes. However, none of the hormones tested affected the kinetic properties of hepatocyte pyruvate kinase, suggesting the absence of covalent modification control of the enzyme. The data indicate that the freezing-stimulated production of large quantities of glucose as a cryoprotectant by R. sylvatica liver does not involve qualitative differences in the hormonal control of liver glycogenolysis, compared with other lower vertebrates. However, quantitative differences were seen, such as the much greater phosphorylase activity, 4.38 +/- 0.33 mumol min-1 g-1 packed cells, in freshly isolated R. sylvatica hepatocytes compared with 0.36 +/- 0.06 mumol min-1 g-1 in Rana pipiens hepatocytes.
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PMID:Hormonal effects on glycogen metabolism in isolated hepatocytes of a freeze-tolerant frog. 162 97

Glucagon injected subcutaneously or intramuscularly may take up to 30 min to reverse hypoglycaemia. We investigated whether glucagon absorption could be accelerated by two manoeuvres known to enhance insulin absorption: addition of a powerful local hyperaemic agent (10 nmole alpha-calcitonin gene-related peptide; CGRP), and injection using a multihole 'sprinkler' needle. Glucagon (1 mg) given by conventional injection to six normal subjects produced peak plasma glucagon concentrations of 1.48 +/- 0.23 (SEM) ng ml-1 after 20 min and a peak glycaemic response of 7.8 +/- 0.8 mmol l-1 at 25 min. Glucagon injected with CGRP or using the sprinkler needle did not produce any significant differences in plasma glucagon or glycaemia profiles, compared with conventional injection. Further studies demonstrated that glucagon is itself a powerful vasodilator, causing a 300-500% increase in local blood flow, comparable to that induced by CGRP. Because of its intense local hyperaemic action, the absorption of subcutaneously-injected glucagon may be optimal and seems unlikely to be accelerated by pharmacological or other means.
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PMID:Attempts to accelerate glucagon absorption: effects of adding a vasodilator and of injection using a 'sprinkler' needle. 163 39

In recent years there has been great concern that human insulin (HI) may induce fewer hypoglycaemic warning symptoms than porcine insulin (PI). We addressed this issue in eight patients aged 25.6 +/- 3.3 (SEM) years with Type I (insulin-dependent) diabetes mellitus of 15.1 +/- 3.7 years duration who complained that hypoglycaemia unawareness had appeared after transferring from PI to HI. Acute induction of hypoglycaemia was induced on two occasions with semisynthetic HI and purified PI under double-blind conditions. Blood glucose was first clamped for 2 h at 4.4-6.7 mmol l-1 with an intravenous infusion of HI or PI at 50 mU kg-1 h-1 and 20% glucose at a variable rate. Thereafter, insulin infusion alone was maintained for 100 minutes. Heart rate, arterial pressure, reflex times, autonomic and neuroglycopenic signs and symptoms were assessed every 10 min. Arterialized venous blood samples were taken to measure blood glucose every 10 min and catecholamines, insulin, glucagon, growth hormone, and cortisol every 20 min. Autonomic symptoms first appeared at a plasma glucose level of 2.92 +/- 0.21 mmol l-1 with HI vs 2.92 +/- 0.48 mmol l-1 with PI (NS). There were no significant differences between the two studies concerning any of the above mentioned clinical parameters or the counterregulatory hormone responses. A differential effect of insulin species on the ability to perceive hypoglycaemia in patients who ascribed diminished perception of hypoglycaemia to the use of HI was thus not observed.
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PMID:Symptomatic and hormonal hypoglycaemic responses to human and porcine insulin in patients with type I diabetes mellitus. 164 99

In order to observe whether the improvement of diabetic control would promote insulin release of elder non-insulin-dependent diabetics, we performed oral glucose tolerance test and glucagon infusion in eight patients before and after fasting plasma glucose normalized with insulin therapy for three weeks. The levels of plasma glucose and C-peptide both on fasting and following intravenous glucagon infusion and oral glucose loading were measured. Their ages ranged from 60 to 72 years old. The initial fasting plasma glucose levels were 261 +/- 18 mg/dl (Mean +/- SEM). After insulin therapy for three weeks, the fasting plasma glucose levels dropped to 130 +/- 8 mg/dl (Mean +/- SEM, P less than 0.001). The fasting C-peptide/glucose ratio showed no difference before and after therapy. On the other hand, the C-peptidogenic index was markedly improved following insulin therapy, as compared with the value before therapy (P less than 0.05). These results suggested that greater C-peptide response was found in non-insulin dependent elderly diabetics following oral glucose after plasma glucose normalized with insulin therapy.
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PMID:Insulin treatment improved glucose-induced insulin release in elderly non-insulin-dependent diabetes mellitus, secondary failure to oral hypoglycemic agents. 164 73

1. Splanchnic haemodynamic changes were studied in seven healthy subjects during hypoglycaemia induced by the intravenous infusion of insulin. Superior mesenteric artery blood flow and cardiac output were examined noninvasively by a Doppler ultrasound technique. 2. Blood glucose concentration fell from 4.5 (0.14) mmol/l basally to 1.5 (0.09) mmol/l [mean (SEM), P less than 0.003] at the hypoglycaemic reaction ('R') and recovered to baseline by 'R' + 60 min. There was an associated rise in plasma glucagon, adrenaline and noradrenaline levels. 3. Superior mesenteric artery blood flow rose at 'R' from a basal value of 532 (38) ml/min to a peak of 803 (73) ml/min at 'R' + 10 min [mean (SEM), P less than 0.005] and remained significantly elevated until 'R' + 40 min. Resistance in this vessel fell by 33% at 'R' + 10 min (P less than 0.005) and remained significantly low until 'R' + 40 min. 4. Cardiac output rose by 33% at 'R' (P less than 0.004) and returned to normal by 'R' + 20 min. This was associated with a 24% rise in pulse rate (P less than 0.03), but no change in stroke volume or mean arterial pressure. Total peripheral resistance fell by 21% at 'R' (P less than 0.005) and had returned to normal by 'R' + 20 min. 5. The sustained rise in splanchnic blood flow during hypoglycaemic recovery may be of homoeostatic importance by providing metabolic fuel to the liver for gluconeogenesis.
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PMID:Splanchnic haemodynamic changes during acute hypoglycaemia in man. 165 99

Some insulin-dependent diabetic patients who have clear symptoms of hypoglycaemia during animal insulin treatment have reported loss of these symptoms when human insulin preparations are introduced. A survey of Mersey Region, UK, identified eleven patients whose awareness of hypoglycaemia was lost after introduction of human insulin but returned with animal insulin treatment; seven took part in the study. Acute hypoglycaemia was induced in these patients on two occasions by intravenous infusion of porcine or human soluble insulin (2.5 mU.kg-1, min-1) in random order. There was no significant difference between porcine and soluble insulin in the plasma glucose profile; mean (SEM) plasma glucose fell from 7.1 (0.4) mmol/l to a nadir of 1.5 (0.1) mmol/l with porcine insulin and from 7.1 (0.5) mmol/l to 1.6 (0.2) mmol/l with human insulin. An acute autonomic reaction occurred in all seven patients, at a similar plasma glucose concentration (1.9 [0.1] mmol/l with porcine insulin; 2.0 [0.2] mmol/l with human insulin). There were no significant differences in the frequency of symptoms or signs of hypoglycaemia between the two insulin species, nor any consistent differences in plasma glucagon, cortisol, growth hormone, adrenaline, or noradrenaline responses to hypoglycaemia. Symptomatic and hormonal responses to acute hypoglycaemia induced by porcine and human soluble insulins therefore seem to be almost indistinguishable, even in patients carefully selected for their apparent loss of hypoglycaemia awareness with human insulin.
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PMID:Human insulin and awareness of acute hypoglycaemic symptoms in insulin-dependent diabetes. 168 Dec 96

The present study was designed to determine in humans the dose of CCK which suppresses food intake. 18 male subjects received in randomized order either i.v. saline or Thr28 Nle31 CCK 25-33 (CCK-9) at 100 or 500 pmol/kgh, respectively. In addition, 7 subjects received CCK together with the opiate receptor antagonist naloxone to examine if activation of endogenous opioids might interfere with the potential satiating effect of CCK. Food intake during saline was 32 +/- 2 sandwiches (mean +/- SEM), during CCK-9 100 pmol/kgh 28 +/- 2 (n.s.) and only 12 +/- 3 during CCK-9 500 pmol/kgh (p less than 0.01). The respective water intake was 730 +/- 70 ml, 590 +/- 60 ml (n.s.) and 320 +/- 50 ml (p less than 0.01). Naloxone further reduced food and water intake during high but not low dose CCK or saline. During saline postprandial insulin levels rose by 49 +/- 6 microU/ml within 45 min which was attenuated during low dose (23 +/- 6 microU/ml; p less than 0.01) and high dose CCK-9 (1 +/- 1 microU/ml; p less than 0.001). Plasma glucagon did not change in control or CCK experiments. The postprandial rise of pancreatic polypeptide was attenuated during high dose CCK. Naloxone had no effect on the hormonal response except for a prolonged reduction of insulin and glucose levels following high dose CCK + naloxone. Plasma CCK levels rose by 5.4 pmol/l in controls but by 55 and 255 pmol/l during the low and high dose CCK infusion, respectively. These data demonstrate that suppression of food intake in man by i.v. CCK is a pharmacological rather than a physiological effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of CCK on food intake in man: physiological or pharmacological effect? 171 70

Muscarinic blockade by atropine has been shown to decrease the thermic effect of a mixed meal, but not of intravenous glucose. To further delineate the mechanisms involved in the atropine-induced inhibition of thermogenesis after a meal, plasma substrate and hormone concentrations, energy expenditure (EE) and substrate oxidation rates were measured before and during a continuous glucose infusion (44.4 mumol.kg-1.min-1) with or without atropine. After 2 h of glucose infusion, a 20-g oral fructose load was administered while the glucose infusion was continued. Plasma insulin concentrations attained a plateau at 596 (SEM 100) pmol.l-1 after 120 min of glucose infusion and were not affected by muscarinic blockade; plasma glucose concentrations peaked at 13.3 (SEM 0.5) mmol.l-1 at 90 min and decreased progressively thereafter; no difference was observed with or without atropine. Plasma free fatty acid and glucagon concentrations, with or without atropine, were both decreased to 201 (SEM 18) mumol.l-1 and 74 (SEM 4) ng.l-1, respectively, after 2 h of glucose infusion, and were not further suppressed after oral fructose. Carbohydrate oxidation rates (CHO(ox)) increased to 20.8 (SEM 1.4) mumol.kg-1.min-1 and lipid oxidation rates (Lox) decreased to 1.5 (SEM 0.3) mumol.kg-1.min-1 between 90 and 120 min after the beginning of glucose infusion and were not affected by atropine. Glucose-induced thermogenesis was similar with [6.5% (SEM 1.4%) of basal EE] or without [6.0% (SEM 1.0%), NS) muscarinic blockade during the 30 min preceding fructose ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of muscarinic blockade on the thermic effect of oral or intravenous carbohydrate. 176 Oct 15

We have previously reported that the combination of IFN-gamma plus TNF-alpha is able to induce the de novo expression of HLA class II on human beta cells. In the present study, we have investigated the effect of these cytokines, alone or in combination, on the function and viability of human islet cells in vitro. Three hour insulin release was markedly reduced in human islet monolayer cultures after 4 days' exposure to 1000 U/ml of the combination TNF-alpha plus IFN-gamma (36.7 +/- 7.7, % of the control +/- SEM) or to TNF-alpha alone (49.5 +/- 7% of the control) while IFN-gamma had little effect. On direct inspection cell damage was clearly detected only in the cultures treated with TNF-alpha plus IFN-gamma in which staining by indirect immunofluorescence (IFL) for insulin revealed that the number of beta cells was also significantly reduced, thus suggesting a real cytotoxic effect of this cytokine combination. This effect was not beta cell specific since glucagon release and the number of alpha cells were also reduced in the cultures exposed to IFN-gamma plus TNF-alpha. 51Cr release experiments supported the cytoxicity of these cytokines to normal islet cells. There was a time course relationship between class II induction (2 days) and the cytotoxic effect of IFN-gamma plus TNF-alpha (4 days) on the same islet cells. In conclusion, these results indicate that the combination of IFN-gamma and TNF-alpha exerts a cytotoxic effect on human islet cells in vitro.
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PMID:Cytotoxic effect of IFN-gamma plus TNF-alpha on human islet cells. 190 37


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