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)

Streptozotocin (STR), an agent known to induce damage of pancreatic B cells in mammals, was used to study changes of plasma insulin concentration and hepatic insulin-like growth factor I (IGF-I) mRNA levels in juvenile coho salmon, Oncorhynchus kisutch. Fish were injected intraperitoneally with either 200 mg/kg body wt STR or the vehicle. All fish fed and grew throughout the experiment; however, the STR-injected fish had lower instantaneous growth rates than control fish (1.4% and 2.1%, correspondingly). Plasma insulin concentration and hepatic IGF-I mRNA levels in STR-treated fish were significantly lower than in the control fish, whereas there was no difference between the two groups of fish in plasma concentrations of either glucagon or growth hormone. Impaired insulin production caused by STR injection was either coincident with or slightly preceded reduction in hepatic IGF-I mRNA expression, implying that insulin may affect IGF-I production and, consequently, fish growth.
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PMID:Insulin and insulin-like growth factor I in coho salmon Oncorhynchus kisutch injected with streptozotocin. 797 72

Since the development of recombinant DNA technology, there has been a rapid expansion of interest in the use of human insulin-like growth factor I (IGF-I) synthesized by recombinant DNA technology for the treatment of clinical disorders. This article reviews recent studies of the metabolic effects of recombinant human IGF-I in normal humans. These studies demonstrated that under euglycemic conditions, IGF-I had potent effects on glucose (hepatic and peripheral), lipid and amino acid metabolism that closely resemble those of insulin, despite a concomitant inhibitory effect on insulin secretion. Hypoglycemia produced by IGF-I infusions (free-fall study and glucose clamps) had a different effect on counterregulatory responses compared with insulin. The glucagon response was absent, growth hormone (GH) release was attenuated, while norepinephrine levels were increased. Suppression of glucagon release during hypoglycemia impaired glucose recovery. Paradoxically, awareness of hypoglycemia was enhanced with IGF-I, partly due to stimulation of sympathetic activity. Studies performed under hyperglycemic conditions showed that IGF-I inhibited glucose-stimulated insulin secretion, but that this inhibitory effect was partially overcome by increasing the hyperglycemic stimulus. Moreover, despite the decrease in insulin secretion, glucose disposal was accelerated by IGF-I. These observations imply that IGF-I might be effective in human diabetes. In particular, normalization of the decreased basal IGF-I levels, which are characteristic of poorly controlled patients with insulin-dependent diabetes mellitus (IDDM), in pubertal patients might lower glucagon and GH levels and improve cellular metabolism in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic effects of insulin-like growth factor I in normal humans. 808 11

The anabolic actions of GH are well known, although specific tissue responses and the mechanism of nitrogen conservation are less well understood. This study was designed to examine the acute metabolic effects of GH on whole body and regional protein metabolism, using an experimental protocol which controlled for confounding perturbations in other hormones by a simultaneous infusion of somatostatin. Control subjects received replacement doses of insulin, glucagon, and GH for the entire 7-h study period, whereas GH subjects received an identical protocol, except for an increased dose of GH sufficient to increase serum concentrations into the high-physiological range (12-20 ng/mL) for the final 3.5 h of the study (P < 0.001). Thirteen young, healthy male subjects were studied in the postabsorptive period; five served as control subjects and eight as treatment (GH) subjects. Each received continuous iv infusions of somatostatin, L-[13-C]leucine, and L-[2H5]phenylalanine throughout the study. Femoral arterial and venous sampling allowed for simultaneous measurements across the leg and in the whole body. C-Peptide levels were suppressed throughout the infusion; insulin, glucagon, insulin-like growth factor I, cortisol, epinephrine, norepinephrine, and glucose concentrations were not different between groups. Glycerol concentrations increased 3-fold in GH subjects during the final 3.5-h period (P = 0.04). Concentrations of several amino acids declined through the study, but no differences were observed between treatment groups. Leucine oxidation was reduced in GH compared to control subjects (P = 0.04). No changes in CO2 production or whole body leucine or phenylalanine flux were observed, whereas nonoxidative disposal of leucine was marginally higher in GH compared to control subjects (P = 0.07). By contrast, rates of appearance and disappearance of both leucine and phenylalanine across the leg all were relatively lower in GH compared to control subjects; leucine balance across the leg was reduced by GH (P = 0.03), whereas phenylalanine balance was not influenced by GH. Our data thus demonstrate an acute stimulatory effect of GH on lipolysis, a decrease in leucine oxidation, and no stimulation of muscle protein synthesis in spite of enhanced protein synthesis in nonmuscle tissue.
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PMID:Acute growth hormone effects on amino acid and lipid metabolism. 817 57

To elucidate the effects of insulin-like growth factor I (IGF-I) on fuel oxidation and insulin sensitivity, eight healthy subjects were treated with saline and recombinant human (IGF-I (10 micrograms/kg.h) during 5 d in a crossover, randomized fashion, while receiving an isocaloric diet (30 kcal/kg.d) throughout the study period. On the third and fourth treatment days, respectively, an L-arginine stimulation test and an intravenous glucose tolerance test were performed. A euglycemic, hyperinsulinemic clamp combined with indirect calorimetry and a glucose tracer infusion were performed on the fifth treatment day. IGF-I treatment led to reduced fasting and stimulated (glucose and/or L-arginine) insulin and growth hormone secretion. Basal and stimulated glucagon secretion remained unchanged. Intravenous glucose tolerance was unaltered despite reduced insulin secretion. Resting energy expenditure and lipid oxidation were both elevated, while protein oxidation was reduced, and glucose turnover rates were unaltered on the fifth treatment day with IGF-I as compared to the control period. Enhanced lipolysis was reflected by elevated circulating free fatty acids. Moreover, insulin-stimulated oxidative and nonoxidative glucose disposal (i.e., insulin sensitivity) were enhanced during IGF-I treatment. Thus, IGF-I treatment leads to marked changes in lipid and protein oxidation, whereas, at the dose used, carbohydrate metabolism remains unaltered in the face of reduced insulin levels and enhanced insulin sensitivity.
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PMID:Insulin-like growth factor I stimulates lipid oxidation, reduces protein oxidation, and enhances insulin sensitivity in humans. 822 40

Insulin-like growth factor I (65 micrograms/kg) or insulin (0.1 IU/kg) were injected i.v. on two separate occasions in random order in normal and in Type 2 (non-insulin-dependent) diabetic subjects. Insulin-like growth factor I and insulin injection resulted in identical decrements of plasma glucose concentrations after 30 min but in delayed recovery after insulin-like growth factor I as compared to insulin in both groups (p < 0.05 insulin-like growth factor I vs insulin). Counterregulatory increases in plasma glucagon, adrenaline, cortisol and growth hormone concentrations after hypoglycaemia (1.9 +/- 0.2 mmol/l) in normal subjects were blunted after insulin-like growth factor I administration compared to insulin (p < 0.05). Plasma glucose in Type 2 diabetic subjects did not reach hypoglycaemic levels but the acute glucose decrease to 4.5 +/- 0.8 mmol/l was associated with significantly lower responses of plasma glucagon and adrenaline but higher cortisol levels after insulin-like growth factor I compared to insulin (p < 0.003). Plasma concentrations of non-esterified fatty acids and leucine decreased similarly after insulin-like growth factor I and insulin in both groups. The present results demonstrate that insulin-like growth factor I is capable of mimicking the acute effects of insulin on metabolic substrates (plasma glucose, non-esterified fatty acids, leucine). The decreases of plasma glucose were similar after both peptides in normal and in diabetic subjects who were presumably insulin resistant. Counterregulatory hormone responses to plasma glucose decrements differed, however, between insulin-like growth factor I and insulin and in the diabetic and the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of recombinant human insulin-like growth factor I and insulin on counterregulation during acute plasma glucose decrements in normal and type 2 (non-insulin-dependent) diabetic subjects. 824 78

Recombinant human growth hormone (rhGH) administration to normal volunteers increases estimates of whole-body and forearm protein synthesis but has little effect on rates of proteolysis in both the postabsorptive state and during meal absorption. In contrast, insulin decreases estimates of whole-body and forearm proteolysis while decreasing or, in the presence of infused (or ingested) amino acids, sustaining estimates of protein synthesis. We have used high-dose prednisone as a controlled model for protein catabolism in normal volunteers and demonstrated that glucocorticosteroids increase estimates of whole-body proteolysis and the oxidation of leucine with little or no effect on estimates of whole-body protein synthesis. We have recently demonstrated that high-dose rhGH together with prednisone prevents the protein-catabolic effects observed with treatment with prednisone alone, while inducing insulin resistance and increased secretion of proinsulin. GH is thought to mediate its effects via the generation of insulin-like growth factor I (IGF-I). However, high rates of infusion of rhIGF-I induce hypoglycemia and decrease estimates of whole-body proteolysis and suppress the secretion of GH, insulin and glucagon, suggesting a predominant insulin-like effect on protein and glucose metabolism. When rhIGF-I is infused at a rate that achieves plasma IGF-I concentrations similar to those observed during rhGH treatment and yet avoids hypoglycemia, estimates of proteolysis and protein synthesis were not affected in the absence or presence of prednisone treatment. When rhGH and rhIGF-I are administered simultaneously, nitrogen balance is remarkably improved. Thus, the mechanism of action of both rhGH and/or rhIGF-I on body protein metabolism remains to be elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of human growth hormone and insulin-like growth factor I on whole-body leucine and estimates of protein metabolism. 830 55

GH hypersecretion in insulin-dependent diabetes (IDDM) is well documented. Although it has recently been shown that residual insulin secretion determines the magnitude of this GH hypersecretion, the underlying mechanisms of the disorder have not yet been clarified. The 24-h GH and blood glucose profiles, insulin-like growth factor I (IGF-I) concentrations and GH responses to GRF were analyzed in 21 insulin-dependent diabetics and 4 healthy subjects before and after 7 days treatment with recombinant human GH (rhGH) (4 IU given sc at 0800 h). According to C-peptide response to glucagon IDDM patients were subdivided into C-peptide negative (CpN, n = 12) patients without endogenous pancreatic beta-cell activity and C-peptide positive (CpP, (n = 9) patients with endogenous insulin secretion. No significant difference could be observed between the mean 24-h blood glucose profile before and after rhGH treatment in any treated group. Before and on rhGH treatment the highest 24-h GH values were observed in CpN patients when compared to CpP and controls. The rhGH treatment induced a similar increase in the mean 24-h GH concentrations in all groups studied which was statistically significant only in CpP diabetics. Mean pretreatment serum IGF-I concentrations were not significantly different between CpN, CpP patients and controls. The net increase in IGF-I concentrations after rhGH treatment was however, significantly lower in CpN patients than in CpP and control subjects. GRF-induced GH response before and after rhGH treatment was significantly greater in diabetics than in controls. The response of GH to GRF in CpN diabetics was however, almost unchanged after treatment whereas it became lower in CpP diabetics and controls. The dose of 4 IU of rhGH increased significantly GH levels in diabetics with preserved beta-cell function with consequent increase in IGF-I levels and attenuation of GRF induced GH response. In contrast, the same dose of rhGH failed to induce significant increase in GH levels in diabetics without residual beta-cell activity, most probably due to already high pretreatment levels. In addition, neither increase in IGF-I levels nor suppression of GH response to GRF on rhGH treatment was observed in CpN diabetics. The results are in keeping with an important role of portal insulin in GH-induced hepatic IGF-I secretion.
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PMID:The effect of recombinant human growth hormone on regulation of growth hormone secretion and blood glucose in insulin-dependent diabetes. 832 51

To determine if insulin-like growth factor I (IGF-I) inhibits pulsatile growth hormone (GH) secretion in man, recombinant human IGF-I (rhIGF-I) was infused for 6 h at 10 micrograms.kg-1.h-1 during a euglycemic clamp in 10 normal men who were fasted for 32 h to enhance GH secretion. Saline alone was infused during an otherwise identical second admission as a control. As a result of rhIGF-I infusion, total and free IGF-I concentrations increased three- and fourfold, respectively. Mean GH concentrations fell from 6.3 +/- 1.6 to 0.59 +/- 0.07 micrograms/liter after 120 min. GH secretion rates, calculated by a deconvolution algorithm, decreased with a t 1/2 of 16.6 min and remained suppressed thereafter. Suppression of GH secretion rates occurred within 60 min when total and free IGF-I concentrations were 1.6-fold and 2-fold above baseline levels, respectively, and while glucose infusion rates were < 1 mumol.kg-1.min-1. During saline infusion, GH secretion rates remained elevated. Infusion of rhIGF-I decreased the mass of GH secreted per pulse by 84% (P < 0.01) and the number of detectable GH secretory pulses by 32% (P < 0.05). Plasma insulin and glucagon decreased to nearly undetectable levels after 60 min of rhIGF-I. Serum free fatty acids, beta-hydroxybutyrate, and acetoacetate were unaffected during the first 3 h of rhIGF-I but decreased thereafter to 52, 32, and 50% of levels observed during saline. We conclude that fasting-enhanced GH secretion is rapidly suppressed by a low-dose euglycemic infusion of rhIGF-I. This effect of rhIGF-I is likely mediated through IGF-I receptors independently of its insulin-like metabolic actions.
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PMID:A low dose euglycemic infusion of recombinant human insulin-like growth factor I rapidly suppresses fasting-enhanced pulsatile growth hormone secretion in humans. 851 57

The effect of Orlistat, a lipase inhibitor used in the treatment of obesity was studied on gastrointestinal transit time, on body composition and on hormones known to be influenced by the degree of hydrolysis of nutritional triglycerides or by reduced nutrient intake and absorption. After a placebo run-in period 14 patients were randomized to a 12-week treatment period on Orlistat 360 mg per day (mean body weight 93.1 +/- 9.8 kg) or placebo (mean body weight 90.7 +/- 10.5 kg). At randomization and after 12 weeks body weight, body composition, thyroid hormones, catecholamines, insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were measured. During 4 hours after consumption of a liquid fat-rich mixed meal containing study medication, 15 g lactulose and 25 g xylose, blood levels of glucose, insulin, c-peptide, glucagon, triglycerides, free fatty acids, cholecystokinin, pancreatic polypeptide and xylose and expiration air levels of hydrogen were measured. Weight loss was 4.2 +/- 3.5 kg in the Orlistat group versus 3.0 +/- 1.9 kg in the placebo group. Fat mass decreased to an equal degree, whereas lean body mass remained stable. No differences were found for thyroid hormones, catecholamines, IGF-I and IGFBP-3 levels. By comparing the areas under the curve (AUC) and the peak levels at randomization (acute effects) of insulin and c-peptide a tendency was found to be increased in the Orlistat group, whereas those of xylose were increased significantly, suggesting faster gastric emptying after Orlistat. No differences were found in the other parameters. By comparing the changes in responses (longer term effects) no significant differences were found. In conclusion, the presence in the gut of undigested and unabsorbed fat does not seem to have a relevant influence on hormonal status and body composition in a small group of moderately obese patients.
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PMID:Lipase inhibition and hormonal status, body composition and gastrointestinal processing of a liquid high-fat mixed meal in moderately obese subjects. 865 34

The association of hypoglycemia with nonislet cell tumors is well recognized and in nearly all instances has been related to the production of hormones with insulin-like activity. To determine the mechanism of such tumor-induced hypoglycemia and the response to pharmacological intervention, we studied a 54-yr-old man with refractory hypoglycemia and a large intraabdominal hemangiopericytoma. During a supervised fast, plasma glucose decreased to 2.2 mmol/L. Circulating insulin (< 7 pmol/L), C peptide (< 0.04 nmol/L), and GH levels (< 0.6 microgram/L) were all undetectable, insulin-like growth factor I (IGF-I; 5 nmol/L) was low, IGF-II was in the normal range (87 nmol/L), and free IGF-II and big IGF-II (E1-21 fragment) were elevated at 18 and 142 nmol/L, respectively. On another day, after maintaining euglycemia overnight with a 20% dextrose infusion, a euglycemic (5.0-5.5 mmol/L) glucose clamp study using [3-3H]glucose tracer infusion combined with arteriovenous leg catheterization was performed in the postabsorptive basal state and during 3 h of crystalline somatostatin infusion (0.08-0.24 pmol/kg min). In the postabsorptive state at euglycemia, free IGF-II and big IGF-II remained elevated at 16 and 162 nmol/L, respectively. Whole body glucose disposal was elevated at 21.1 mumol/kg.min, whereas the rate of glucose infusion was 12.1 mumol/kg.min, and depatic glucose output was 7.8 mumol/kg.min. The leg arterio-venous plasma glucose difference was increased at 0.6 mmol/L, as was leg glucose uptake at 203.9 mumol/min. After 3 h of somatostatin infusion, both free and big IGF-II decreased by 35-40% to 10 and 102 nmol/L, respectively. Whole body glucose disposal also decreased to near normal (12.8 mumol/kg.min), whereas leg arterio-venous plasma glucose difference and leg glucose uptake became negligible. The plasma glucose level remained at 5.0-5.5 mmol/L despite a marked fall in hepatic glucose output to 2.9 mumol/kg.min and a decrease in glucose infusion rate to 8.7 mumol/kg.min. During somatostatin treatment, GH remained suppressed at less than 0.6 microgram/L, and glucagon decreased from 99 to 78 ng/L. In this patient with a hemangiopericytoma, hypoglycemia was associated with increased circulating insulin-like activity from elevated free and big IGF-II, which stimulated glucose uptake primarily into muscle tissue. A continuous infusion of crystalline somatostatin effectively reduced the elevated levels of IGF-II and glucose uptake, but was unable to adequately control hypoglycemia without the simultaneous infusion of exogenous glucose or glucagon.
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PMID:Mechanisms of tumor-induced hypoglycemia with intraabdominal hemangiopericytoma. 877 51


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