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)

Four lactating Holstein cows averaging 155 d postpartum were used in a crossover design to examine the influence of somatotropin administration (33 mg/d for 28 d) and dietary CP (11 vs. 16% CP) concentration on physiological responses to single intravenous injections of glucagon, insulin, glucose, and somatotropin. Dietary CP was without influence on plasma hormone or metabolite responses to the challenges but increased basal concentrations of FFA. Basal concentrations of glucagon, glucose, and insulin were not significantly increased by somatotropin treatment; however, there was a tendency for insulin concentrations to be higher in somatotropin-treated cows. Somatotropin treatment increased basal concentrations of somatotropin and FFA. Increases in glucose concentrations after glucagon challenge occurred more quickly, reached a greater peak, and lasted longer for cows treated with somatotropin than for control cows. Insulin concentrations were decreased after somatotropin challenge in control cows, but not in somatotropin-treated cows. Responses of metabolites and hormones to glucose or somatotropin challenges were not influenced by somatotropin treatment. Changes in the metabolism of glucose and insulin suggest that cows treated with somatotropin have a greater ability to synthesize and conserve glucose than control cows. Data obtained support the concept of the homeorhetic action of somatotropin.
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PMID:Effect of somatotropin and dietary protein concentration on hormone and metabolite responses to single injections of hormones and glucose. 264 22

The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects and drug interactions, dosage, availability and cost, and indications for use of octreotide, a new synthetic analogue of the peptide hormone somatostatin (SS), are reviewed. Like SS, octreotide suppresses secretion of pituitary growth hormone (GH) and thyrotropin and decreases release of a variety of pancreatic islet cell hormones including insulin, glucagon, and vasoactive intestinal peptide (VIP). Octreotide also reduces splanchnic blood flow, gastric acid secretion, GI motility, and pancreatic exocrine function and alters the absorption of water, electrolytes, and nutrients from the GI tract. The elimination half-life of i.v. octreotide is 72-98 minutes, compared with 2-3 minutes for i.v. SS. Usual administration of octreotide is by the i.v. or s.c. route. Octreotide has been studied in the treatment of hormone-secreting pituitary tumors and pancreatic islet cell tumors. Octreotide therapy lowers GH secretion and improves clinical symptoms in patients with acromegaly and may suppress clinical symptoms to a greater degree than bromocriptine. Patients with carcinoid syndrome and VIP-secreting tumors (vipomas) have had substantial improvement in clinical symptoms with administration of octreotide. This agent does not appear to be effective in the treatment of nonvariceal upper GI bleeding and acute pancreatitis; its relative usefulness in the treatment of variceal bleeding is not established. Adverse effects associated with octreotide therapy generally have been mild, including pain or burning at the injection site, abdominal pain, and diarrhea. Octreotide has been shown to interfere with absorption of oral cyclosporine. Standard initial therapy is octreotide acetate 50-100 micrograms s.c. every 8-12 hours, with titration based on clinical and biochemical effects. Up to 3000 micrograms/day of octreotide acetate has been administered to patients with acromegaly without serious adverse effect. Octreotide is marketed under the brand name Sandostatin and is available in 1-mL ampuls containing 50, 100, and 500 micrograms of octreotide acetate. Because the conditions for which octreotide appears to be most effective are uncommon, the drug should be considered for addition to the formulary in tertiary-care institutions only; addition of octreotide to the formulary of a community hospital is probably unnecessary. The synthetic analogue octreotide is longer acting and more specific in pharmacologic action than SS.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Octreotide, a new somatostatin analogue. 265 11

Growth hormone (GH) hypersecretion in insulin-dependent diabetes mellitus (IDDM) subjects has been shown to be causally related to early-morning hyperglycemia. We studied the effect of nocturnal GH suppression on acute glycemic control in six IDDM patients during a constant overnight insulin infusion (0.075 mU.kg-1.min-1). In control experiments (infusion of insulin alone), plasma glucose increased from 5.6 +/- 0.6 mM at 2400 to 11.1 +/- 1.3 mM at 0900 (P = .0024). When in addition the cholinergic muscarinic antagonist pirenzepine was given (100 mg at 2200 and again at 2400), plasma glucose increased from 5.6 +/- 0.3 mM at 2400 to 8.4 +/- 1.4 mM at 0900 (P greater than .05). The nocturnal surges of GH that were demonstrated in all patients during the control nights were suppressed during the treatment nights. There were no significant changes in insulin, cortisol, or epinephrine concentrations. Mean glucagon and norepinephrine concentrations. Mean glucagon and norepinephrine concentrations were reduced from 127 +/- 2.7 ng/L and 8.7 +/- 0.5 nM to 101 +/- 1.9 ng/L (P less than .001) and 3.5 +/- 0.2 nM (P less than .001) on control and treatment nights, respectively. Neither glucagon nor norepinephrine concentrations changed significantly between 2400 and 0900 on either control or treatment nights. We conclude that nocturnal GH suppression by pirenzepine during a constant low-rate insulin infusion is associated with an attenuation of the early-morning plasma glucose rise.
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PMID:Early-morning hyperglycemia in IDDM. Acute effects of cholinergic blockade. 225 1

Net flux of insulin, glucagon, somatotropin, somatomedin-C, and somatostatin across the portal-drained viscera and liver of four lactating Holstein cows was measured at 4 and 8 wk postpartum. Cows were fed ad libitum intake a 60:40 corn silage:concentrate diet and milked at 12-h intervals. Milk yield and DM intake were 32.2 and 15.6 kg/d respectively. Twenty-four consecutive measurements of insulin, glucagon, and somatotropin net flux were obtained at 30-min intervals; 12 hourly measurements were obtained for somatomedin-C and somatostatin. Net flux is venous-arterial concentration difference times blood flow. Net flux of somatomedin-C was not detectable across the portal-drained viscera or liver. Somatotropin was removed by total splanchnic tissues. There was net production of somatostatin across portal-drained viscera, but net flux of somatostatin across liver was not significant. On a net basis, removal of insulin and glucagon by liver accounted for 66% of portal-drained visceral production. Within cows and sampling days, increases in net portal-drained visceral production of insulin and glucagon often were mirrored by increases in net removal by liver. As in other species, the bovine liver is an important regulator of circulating concentrations of insulin and glucagon.
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PMID:Net metabolism of hormones by portal-drained viscera and liver of lactating holstein cows. 266 59

Hypoglycemia causes substantial morbidity and some mortality in insulin-dependent diabetes mellitus (IDDM). It is often the limiting factor in attempts to achieve euglycemia. The prevention or correction of hypoglycemia normally involves both dissipation of insulin and activation of glucose counterregulatory systems. Among the latter, glucagon plays a primary role initially, whereas epinephrine is not critical, although it becomes critical when glucagon is deficient. Growth hormone and cortisol play demonstrable roles in recovery from prolonged hypoglycemia. Glucose autoregulation may be involved in defense against severe hypoglycemia. With respect to pathophysiology, counterregulatory systems are involved in at least five clinical glucoregulatory syndromes. Defective glucose counterregulation is associated with, and best attributed to, combined deficiencies of the glucagon and epinephrine responses to plasma glucose decrements. Almost assuredly in concert with hypoglycemia unawareness, it results in a markedly increased frequency of severe hypoglycemia, at least during intensive therapy of IDDM. Defined as a night to morning increase in plasma glucose concentration, the dawn phenomenon is thought to result from dissipation of insulin plus the effects of nocturnal growth hormone secretion. Despite a sound rationale, the clinical relevance of the Somogyi phenomenon has been recently questioned. The clinical impression of altered glycemic thresholds for symptoms, i.e., patients with poorly controlled IDDM suffer symptoms of hypoglycemia at relatively high plasma glucose levels, whereas those with very well-controlled IDDM often tolerate subnormal glucose levels, has received experimental support. Clearly, hypoglycemia in IDDM is a problem that needs to be solved. Numerous issues need to be addressed through both basic and clinical research.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypoglycemia in IDDM. 276 40

Concentrations of insulin, glucagon, growth hormone, adrenocorticotropin, and cortisol were determined in plasma samples obtained at 20-min intervals for 6 h from low and high producing dairy cows at d 30 and 90 postpartum. Four nonpregnant, nonlactating cows also were sampled. Insulin concentrations were reduced at d 30 in both groups of lactating cows compared with concentrations in nonlactating cows; glucagon concentrations were unchanged. The molar insulin: glucagon was reduced at d 30 in both groups and at d 90 for low, but not high producers. Growth hormone concentrations were higher at d 30 in high producers than at d 90, in low producers at d 30, and higher than in nonlactating cows. Cortisol concentrations were lower in high producing cows at d 30 than at d 90 or in nonlactating cows due to a reduced pulse amplitude. No differences were observed for adrenocorticotropin. Reduced molar insulin: glucagon may be an integral response of the cow to lactation, while the difference in the insulin: glucagon for high and low producers at d 90 postpartum may indicate a continued need for a gluconeogenic stimulus in low producers. The elevated growth hormone and low cortisol concentrations likely participate in the enhanced production observed in high producing dairy cows.
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PMID:Plasma concentrations of metabolic hormones in high and low producing dairy cows. 283 86

Many metabolic hormones (glucagon, hydrocortisone, corticosterone, TSH, thyroxine and triiodothyronine) did not stimulate porcine adipose tissue lipolysis in vitro. Growth hormone and ACTH stimulated lipolysis at high concentrations, in the presence of theophylline. Insulin inhibited lipolysis. Infusion of metabolic hormones with measurement of plasma free fatty acid and glycerol concentrations, purportedly indicative of in vivo lipolysis, indicated that glucagon and somatotropin had no effect, adrenocorticotropin increased and insulin depressed plasma concentrations of the metabolites. Overall, the in vitro predicts the in vivo response. There were exceptions, e.g. adrenocorticotropin moderately increased plasma metabolites but had little effect in vitro.
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PMID:Acute effects of metabolic hormones in swine. 287 Aug 58

Growth hormone (GH) is important in diabetes in view of its anti-insulin actions and its relation to the long-term complications of the disease. The suppression of GH secretion in diabetics has theoretical and possible therapeutic interest. Native somatostatin has multiple actions, including inhibition of the secretion of insulin, glucagon, thyroid-stimulating hormone (TSH), and various gut hormones. It also has inhibitory effects on gastrointestinal motility, exocrine secretion, nutrient absorption, and splanchnic blood flow. Its therapeutic use is limited by a duration of effect of several minutes only. SMS 201-995 holds more potential than native somatostatin in view of its longer duration of action. Preliminary data suggest that 50 micrograms SMS 201-995 subcutaneously at night inhibits the nocturnal rise in GH secretion in normal man, but no effect on 24-h GH secretion is observed when SMS 201-995 is injected twice daily before meals. SMS 201-995 inhibits secretion of insulin, glucagon, and TSH in addition to growth hormone and induces carbohydrate intolerance when administered before food in normal subjects. Gastrointestinal side effects suggest additional effects on nutrient disposal, which are important when it is administered before food. Further studies are required to elucidate these effects of SMS 201-995 on endocrine and gastro-intestinal function in normal and diabetic man.
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PMID:Effects of somatostatin and SMS 201-995 on carbohydrate metabolism in normal man. 287 1

The treatment of acromegaly is not optimal at present, since many patients have continued growth hormone hypersecretion. We report the acute effects of a cyclic octapeptide analogue of somatostatin, SMS 201-995 (Sandoz) in 9 nondiabetic, acromegalic patients between the ages of 30 and 74. We report potent and prolonged dose-dependent effects to suppress growth hormone secretion. A single 50 micrograms dose of SMS 201-995 inhibited growth hormone concentration rapidly within 15 minutes, with maximal effect in 75 minutes. Maximal inhibition was of the order of 80%, with absolute concentrations under 2 micrograms/L for about 6 hours in 5 of 7 patients. Growth hormone concentrations remained significantly suppressed below placebo control for up to 24 hours after a single dose of SMS 201-995, but the inhibitory effects on insulin and C-peptide concentrations were limited to 2 hours. The effects on glucagon secretion were minimal, and also evident for only 2 hours. Mild transient postprandial elevations of plasma glucose and FFA were documented. No adverse effects were noted; routine hematology, biochemistry, and vital signs were not altered. Thus SMS 201-995, with preferential effects at the pituitary somatotroph, holds considerable promise as an attractive and viable alternative for treatment of acromegaly.
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PMID:The somatostatin analogue SMS 201-995 in acromegaly: prolonged, preferential suppression of growth hormone but not pancreatic hormones. 288 54

We investigated in 6 acromegalic patients the acute effects on glucose tolerance and insulin secretion of a single sc injection of the somatostatin analogue SMS 201-995, performed 4 h before a mixed meal with xylose administration. Growth hormone levels decreased from 34.0 +/- 20.3 (mean +/- SE) to a minimum of 9.3 +/- 3.0 ng/ml, 3 1/2 h after the injection. A significant inhibition of insulin secretion was also noticed, with a fall from 25.3 +/- 6.4 to 6.3 +/- 2.3 microU/ml at 1 h, and a lower and delayed peak level after the mixed meal. However, the postprandial plasma glucose increase was not different from a control day, while plasma xylose levels were lower. Mean glucagon level after SMS 201-995 was lower than control value in 3 out of the 4 patients in whom it was determined. The decrease of serum growth hormone levels, together with partial glucagon inhibition and, more important, a slowing of intestinal absorptive processes, counterbalanced the inhibitory action of SMS 201-995 on insulin secretion, and no deterioration in carbohydrate tolerance could be demonstrated. However, before SMS 201-995 is employed in the management of acromegalic patients refractory to surgery and bromocriptine therapy, we need further observations of postprandial glycemic profiles during long-term therapy with multiple daily injections of the compound.
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PMID:Effect of a new long-acting somatostatin analogue (SMS 201-995) on glycemic and hormonal response to a mixed meal in acromegalic patients. 289 7


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