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)

In order to investigate the causes underlying metabolic instability in type I diabetes mellitus, we studied 8 unstable (group 1) and 4 well-controlled (group 2) diabetic patients, matched for age and duration of diabetes. Subjects were connected overnight to an artificial pancreas and brought to normoglycemia. On the following morning, insulin administration was discontinued for 6 hours and both metabolic and hormonal studies were carried out during this period. After insulin withdrawal, group 1 showed a faster rise of blood glucose (peak: 324.63 +/- 24.93 vs 175.25 +/- 42.63 mg/dl, p less than 0.01), beta-OH-butyrate (peak: 2,273.25 +/- 415.78 vs 550.50 +/- 158.17 mumol/l, p less than 0.01), and glycerol (164.10 +/- 38.90 vs 28.25 +/- 10.6 mumol/l, p less than 0.01). C-peptide secretion increased in group 2 from 0.09 +/- 0.052 to 0.22 +/- 0.099 pmol/ml whereas it remained almost undetectable in group 1 (p less than 0.01, group 1 vs group 2). Growth hormone, cortisol and immunoreactive glucagon were not significantly different in the two groups at any time after insulin withdrawal. Free insulin, after repeated s.c. or i.m. injection of porcine monocomponent insulin (10 IU), was not different in the two groups. We concluded that type I diabetic patients showing severe metabolic instability produced more glucose, ketone bodies and glycerol after insulin withdrawal than control 'stable' patients. This difference could not be accounted for by an excessive secretion of counterregulatory hormones or by an erratic insulin absorption from the injection sites and may have been related to the degree of B-cell failure, as measured by the absence of C-peptide and/or to the degree of insulin resistance.
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PMID:Metabolic instability in type I diabetic patients. Studies on insulin absorption, hepatic production of metabolites and glucose counterregulation. 390 36

The endocrine basis for control of metabolism in nonthyroidal illness is not yet understood. Burn injury is associated with reduced serum concentrations of thyroid hormones and with resting hypermetabolism. One index of severity is total burn size (TBS, % body surface). After overnight fasting and recumbency, resting metabolic rate (MR, O2 consumption) was measured weekly and plasma was sampled for determination of glucose, total cholesterol, triglycerides, insulin, glucagon, somatostatin, growth hormone, norepinephrine, epinephrine, and cortisol in 28 burned men, 17-23 years old, TBS 2%-85%, including 8 controls with minimal injury (TBS less than or equal to 7.5%). MR was elevated in proportion to burn size mainly in the first week then declined toward normal. Growth hormone was not changed. Two multiple regression analyses (validated by random partitioning of data) determined which plasma variables independently reflected residual variation in MR: without TBS entered as a variable, high MR was associated with elevated glucose, cortisol, and glucagon, and low cholesterol (cumulative r2 = 0.79); with TBS entered, high MR was associated with greater TBS, elevated norepinephrine, and again high glucagon and low cholesterol (r2 = 0.81). Resting metabolism after burn injury is controlled not by the thyroid but may be controlled by a set of antiinsulin hormones that does not include growth hormone, but possibly includes glucagon.
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PMID:Nonthyroidal control of metabolism after burn injury: possible role of glucagon. 401 May 24

1. The administration of glucagon, cAMP [adenosine 3',5'-(cyclic)-monophosphate], BcAMP [6-N-2'-O-dibutyryladenosine 3',5'-(cyclic)-monophosphate] or adrenaline to foetal rats during the last 2 days of gestation evoked the appearance of tyrosine aminotransferase and enhanced the accumulation of glucose 6-phosphatase in the liver. In foetuses 1-2 days younger only BcAMP was effective. After birth liver glucose 6-phosphatase no longer responds to glucagon or BcAMP. Tyrosine aminotransferase is still inducible by these agents in 2-day-old rats, but not in 50-day-old rats. After adrenalectomy of adults glucagon or BcAMP can enhance the induction of the enzyme by hydrocortisone. The results indicate that the ability to synthesize tyrosine aminotransferase and glucose 6-phosphatase when exposed to cAMP develops sooner than the ability to respond to glucagon with an increase in the concentration of cAMP; the responsiveness of enzymes to different hormones changes with age. A scheme illustrating the sequential development of competence in regulating the level of an enzyme is presented. 2. Actinomycin inhibited the effects of glucagon and BcAMP on liver tyrosine aminotransferase and glucose 6-phosphatase in foetal rats. Growth hormone, insulin and hydrocortisone did not enhance the formation of these enzymes. 3. The time-course of accumulation of glucose 6-phosphatase in the kidney is different from that in the liver. Hormones that increase the accumulation in foetal liver do not do so in the kidney of the same foetus or in the livers of postnatal rats.
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PMID:The hormonal regulation of enzymes in penatal and postnatal rat liver. Effects of adenosine 3',5'-(cyclic)-monophosphate. 418 80

Growth hormone release inhibiting hormone (GH-RIH) was infused at a rate of 1.3 mug/min for 28 hours into four patients with acromegaly, two of whom also had clinical diabetes mellitus. Growth hormone and glucagon were suppressed throughout the infusion though delayed secretion of insulin occurred in association with both meals and an oral glucose load. Glucose tolerance was improved in one diabetic patient who was taking chlorpropamide while the other required much less insulin than usual. Secretion of endogenous thyroid-stimulating hormone was lowered in one euthyroid patient on carbimazole. Luteinizing hormone, follicle-stimulating hormone, ACTH, and prolactin were not affected. Serum somatomedin levels were reduced in one patient. There was a rapid rebound of all the suppressed hormones when the infusions stopped. Longer-acting analogues of GH-RIH will be needed before long-term therapy of acromegaly or diabetes mellitus becomes possible, but such preparations should be available soon for clinical trial.
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PMID:Long-term infusion of growth hormone release inhibiting hormone in acromegaly: effects on pituitary and pancreatic hormones. 437 89

The initiation of DNA synthesis has been studied in quiescent primary cultures of fetal rat hepatocytes using defined hormones and chemically defined medium. Preparations of crystalline insulin (0.01-10 microg/ml) or 20,000-fold purified somatomedin (0.01-1 microg/ml) are stimulatory. Growth hormone (0.025 microg/ml) and hydroxycortisone (0.025 microg/ml), 3':5'-GMP! (10(-5) M) fail by themselves to initiate DNA synthesis but added together with insulin, enhance the stimulatory response by 50-100%. Thyroid hormones (L-T(3), L-T(4), 7.5-30 ng/ml) are by themselves without effect, but when they are added to thyroid hormone-depleted serum, the reconstituted mixtures show an enhanced capacity to initiate DNA synthesis. In contrast, glucagon (0.01 microg/ml) inhibits the insulin-stimulated response by about 50% without reducing basal DNA synthesis rates. The results described here and in the accompanying two reports indicate that environmental control over the initiation of DNA synthesis is complex, and can involve the participation of many factors. The in vitro findings are consistent with the concept that liver regeneration is hormonally controlled and raise the possibility that alterations of the intrahepatic ratio of insulin to glucagon are growth regulatory.
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PMID:Growth control of differentiated fetal rat hepatocytes in primary monolayer culture. VII. Hormonal control of DNA synthesis and its possible significance to the problem of liver regeneration. 485 45

Five insulin treated diabetics were studied on three consecutive days. Overnight variable intravenous insulin infusions were used before each study to maintain normoglycaemia and to calculate the optimal basal insulin infusion rate (1.1 +/- 0.1 U/h) which ws then kept constant throughout the study day. A standard 400 kCal breakfast with 25 g xylose was given at 0800 h. When the blood glucose rose above 4.1 mmol/l, an external artificial pancreas was used to infuse either extra insulin (day INS) or somatostatin for either 3h (day som) or the entire 8h experimental period (day SOM). Peak post-prandial blood glucose values were similar on all three days. The blood glucose rebounded after the cessation of the somatostatin infusion on day som. Post-prandial blood xylose peaks were lowered by somatostatin on both days but rebounded after the cessation of the somatostatin infusion on day som. The area under the plasma and urinary xylose curves was lowered by somatostatin only on day SOM. Growth hormone and glucagon levels were not statistically different on all 3 days. Thus somatostatin, when added to an optimal insulin infusion, minimised the insulin requirements by slowing intestinal absorption, but led to rebound hyperglycaemia if not feed-back controlled.
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PMID:Effects of somatostatin added to insulin in a glucose-controlled insulin infusion system. 611 91

The contributions of adrenergic and cholinergic mechanisms to recovery from acute hypoglycaemia induced by insulin (0.15 units/kg i.v.) were examined in eleven normal subjects, six subjects with a pre-ganglionic sympathectomy (adrenergic denervation) and six sympathectomized subjects given atropine (combined adrenergic denervation and cholinergic blockade). Blood glucose recovery was impaired only in the sympathectomized subjects given atropine. The blood lactate response was reduced and the rise in free fatty acids was delayed in both groups of sympathectomized subjects, in whom the normal rises of plasma cyclic AMP and noradrenaline were absent. The plasma pancreatic glucagon response was appropriate to the prevailing blood glucose concentrations in all three groups. The cortisol response was impaired and the pattern of ACTH secretion was abnormal in sympathectomized subjects given atropine. Growth hormone levels were higher in both sympathectomized groups. Blood glucose homeostasis was impaired during combined adrenergic denervation and cholinergic blockade. Glucagon secretion was activated independently of vagal control. In the sympathectomized group given atropine, the rise in plasma cortisol was blunted despite a greater degree of hypoglycaemia. A blockade of central cholinergic receptors producing impaired activation of ACTH secretion at hypothalamic level may explain, at least in part, this delayed restoration of normoglycaemia.
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PMID:Autonomic neural control mechanisms of substrate and hormonal responses to acute hypoglycaemia in man. 627 18

In insulin-dependent diabetics, insulin requirements increase significantly after 0600 h, resulting in prebreakfast hyperglycemia with either conventional insulin therapy or constant insulin infusions with insulin infusion devices. In order to clarify the role of the pituitary-adrenocortical axis and further examine the mechanisms of the phenomenon of nocturnal variability in insulin requirements, we studied five IDDs using a closed-loop insulin infusion device (Biostator, GCIIS). The subjects were given saline (SAL) or dexamethasone (DEX) i.v. from 1800 to 0900 h on successive nights. From 2400-0300 to 0600-0900 h, mean insulin infusion rates required to maintain blood glucose values between 109 and 120 mg/dl increased by 0.21 +/- 0.05 mU/kg/min during the SAL infusion, and 0.16 +/- 0.04 mU/kg/min during the DEX infusion, when plasma cortisols were suppressed to less than or equal to 2 micrograms/dl. Mean free insulin concentrations did not increase and remained constant throughout both study nights in spite of the significantly higher 0600-0900-h insulin infusion rates. Growth hormone, glucagon, epinephrine, and norepinephrine concentrations showed normal nocturnal and early morning patterns during both study nights. We conclude that the nocturnal variability in insulin requirements persists despite suppression of the pituitary-adrenocortical axis, and that increased free insulin clearance or degradation may contribute to the "dawn phenomenon" of rising prebreakfast glucose despite constant insulin infusion.
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PMID:Examination of the role of the pituitary-adrenocortical axis, counterregulatory hormones, and insulin clearance in variable nocturnal insulin requirements in insulin-dependent diabetes. 634 Nov 22

We infused growth hormone into normal subjects in doses that raised circulating hormone to levels (30-35 ng/ml) similar to those seen during stress. Growth hormone excess failed to alter fasting glucose and somatomedin concentrations. However, non-esterified fatty acids and ketones increased by 50% (p less than 0.05) and 120% (p less than 0.01), respectively, despite 35% higher plasma insulin concentrations. When oral glucose was ingested 5 h after initiating the growth hormone infusion, plasma glucose rose by 2-2.5 mmol/l above control (saline infusion) values and the area under the glucose curve increased twofold (p less than 0.005). This occurred in the face of twofold higher insulin levels and normal suppression of glucagon. Growth hormone also did not affect the hyperglycaemic response to a combined infusion of cortisol, glucagon and adrenaline, but accentuated the rise in non-esterified fatty acids, ketones, and insulin caused by these hormones. Our data suggest that growth hormone excess rapidly produces insulin antagonistic effects that may contribute to stress-induced glucose intolerance and lipolysis, even though fasting glucose levels remain unchanged.
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PMID:Effect of growth hormone on oral glucose tolerance and circulating metabolic fuels in man. 634 Nov 44

Phlorizin and 1,3-butanediol were used to determine effects of glucosuria and ketonemia on concentrations of metabolites in blood plasma and on kinetics of glucose metabolism. Four steers received four treatments (control; control plus dietary 1,3-butanediol; control plus phlorizin injections; and control plus phlorizin and 1,3-butanediol) in a Latin square design. Treatments lasted 14 days. All steers received a 30% grain, 70% forage ration in equal meals every 2 h. Metabolite concentrations in blood plasma and urine and glucose kinetics were measured on each of the last 3 days of each treatment period. Phlorizin caused glucosuria; decreased plasma glucose, glucose total entry rate, and glucose recycling; and increased plasma free fatty acids and glucose irreversible loss. Glucose pool size was increased by 1,3-butanediol. Phlorizin plus 1,3-butanediol caused glucosuria and ketonuria; decreased plasma glucose; and increased blood ketone bodies, plasma free fatty acids, glucose irreversible loss, and glucose pool size. Growth hormone, insulin, and glucagon were not affected by treatment. Physiological perturbations in these steers were characteristic of some of those in ketotic cows.
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PMID:Glucose kinetics, plasma metabolites, and endocrine responses during experimental ketosis in steers. 638 28


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