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)

The insulinlike growth factors (IGFs) circulate in association with insulinlike growth factor binding proteins (IGFBPs) that modulate IGF action, but mechanisms of IGFBP regulation are poorly understood. We investigated the regulation of IGFBPs in primary cultures of rat hepatocytes, measuring the appearance of export proteins by ligand blotting after separation via SDS/PAGE, and evaluating mRNA with cDNA probes. Northern blotting studies revealed that IGFBP-1 was expressed at high levels in cultured hepatocytes, in which sustained release of both insulinlike growth factor I and albumin marks preservation of differentiated status. In contrast, transcripts of IGFBP-3 and IGFBP-2 were not detected. Release of IGFBP-1 was unaffected by exposure to glucose (20-500 mg/dl) or to provision of amino acids (0.25-6.25 times normal rat arterial plasma levels). Hormonal studies revealed little effect of glucagon, inhibition by insulin, stimulation by dexamethasone, and blunting of dexamethasone effects by added insulin. Adding dexamethasone provided progressive stimulation: 5-, 11-, and 26-fold at 10(-9), 10(-8), and 10(-7) M, all P less than 0.01; increases in IGFBP-1 protein (ligand blot) and IGFBP-1 mRNA (Northern blot) were highly correlated (r = 0.62, P less than 0.001). In contrast, adding insulin resulted in progressive suppression of both IGFBP-1 protein and IGFBP-1 mRNA, 43% at 10(-10) M, 74% at 10(-9) M, and 83% (maximal) at 10(-8) M; ED50 of approximately 10(-10) M is within the physiological range of insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nutrition and somatomedin XXIX. Molecular regulation of IGFBP-1 in hepatocyte primary culture. 137 36

Previous cross-sectional studies have suggested that lower levels of insulin-like growth factor-1 (IGF-1) in older persons are related in part to diminished physical exercise. However, it is unknown whether the introduction of long-term exercise in previously inactive older individuals increases IGF-1, and whether the response is different between older men and women. Thus, we examined the effects of 8 weeks of endurance training on changes in IGF-1, IGF-1 binding protein-1 (IGFBP-1), IGFBP-3, and maximal aerobic power (VO2max) in 18 older individuals (aged 66.1 +/- 1.4 years, 10 men and eight women). Individuals were also characterized for changes in body composition, estimated energy intake, and fasting plasma levels of glucose, insulin, and glucagon before and after an exercise training program. Endurance training increased VO2max similarly in men (14%, P < .01) and women (14%, P < .01), but women showed a smaller increase in IGF-1 (8%, NS) than men (19%, P < .01). The correlation between changes in VO2max and IGF-1 was significant in men (r = .79, P < .02), but not in women (r = .22, NS). Although no mean group change in IGFBP-1 or IGFBP-3 was noted, the individual changes between IGF-1 and IGFBP-3 showed a tendency to be related in men (r = .48, P = .15), but not in women (-.21, NS). Exercise training decreased plasma glucose (P < .05) in men, but not in women.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The influence of endurance training on insulin-like growth factor-1 in older individuals. 752 25

Regulation of the production of insulin-like growth factor (IGF)-I, IGF-II, IGF binding proteins (IGFBPs), and their related proteins by various hormones was investigated in primary cultures of rat liver parenchymal and nonparenchymal cells. Freshly isolated parenchymal cells contained mRNAs of IGF-I, IGF-II, IGFBP-1, IGFBP-4, growth hormone (GH) receptor, and the acid-labile subunit (ALS), which forms a ternary complex with IGF-I and IGFBP-3; however, parenchymal cells did not express the IGFBP-3 gene. In contrast, nonparenchymal cells contained IGFBP-3 mRNA exclusively, as we reported previously [Takenaka et al. Agric. Biol. Chem., 55, 1191-1193 (1991)]. Cultured rat parenchymal cells produced IGF-I, IGFBP-1, and IGFBP-4 prominently. In these cells, secretion of IGF-I and the content of IGF-I mRNA was greatly increased in the presence of GH in the medium. Insulin also increased the production of IGF-I. Secretion of IGFBP-1 into the medium was enhanced by treatment with glucagon, dibutyrylcyclic AMP (Bu2cAMP), and dexamethasone (Dex) and these enhancements with glucagon and Dex reflected the increase in its mRNA content. Insulin depressed the secretion of IGFBP-1. The content of IGFBP-4 in the parenchymal cells was increased by insulin, Bu2cAMP, and triiodothyronine (T3), thereby enhancing the production of IGFBP-4 and secretion into the medium. Cultured liver nonparenchymal cells of rats produced IGFBP-1, IGFBP-3, and IGFBP-4. Secretion of IGFBP-1 was increased by Bu2cAMP in the medium, that of IGFBP-3 by IGF-I, and that of IGFBP-4 by both IGF-I and Bu2cAMP. Regulation of the production of IGFBP-3 by IGF-I was demonstrated in these investigations. These results suggest that GH increases production of IGF-I in the parenchymal cells and this IGF-I, in turn, increases the production of IGFBP-3 in nonparenchymal cells. As we found GH also increases ALS production in parenchymal cells, by these mechanisms, GH increases the formation of the ternary complex of IGF-I, IGFBP-3, and ALS. This study clearly demonstrates the interrelationship between parenchymal and nonparenchymal cells in the production of IGF-I and IGFBPs in the liver.
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PMID:Production of insulin-like growth factors and their binding proteins in primary cultures of rat liver parenchymal and nonparenchymal cells. 754 2

Insulin-like growth factor-binding protein (IGFBP)-1 is one of six homologous proteins that specifically bind and modulate the mitogenic and metabolic actions of insulin-like growth factor (IGF)-I and IGF-II. Of the six IGFBP, IGFBP-1 is the only one that displays rapid dynamic regulation in vivo, with serum levels varying 10-fold or more in relation to meals. The complementary cDNA for IGFBP-1 was first reported in 1988. The predicted 234-amino acid sequence has a molecular mass of 25.3 kDa. The N-terminal and C-terminal regions are highly homologous among rat, human, and bovine sequences, and contain 18 conserved cysteines which are postulated to provide a framework for ligand binding. The 65-residue midregion is less homologous and does not contain cysteines, but does include a Pro-Glu-Ser-Thr (PEST) domain that is typical of rapidly metabolized proteins. The gene for IGFBP-1 has been localized to human chromosome region 7p12-p14, where it is contiguous with the gene for IGFBP-3. IGFBP-1 mRNA and protein expression have been identified in human liver and uterine decidua, and in nonhuman kidney. In vitro and in vivo studies indicate that insulin is the primary regulator of IGFBP-1 expression in these tissues, and that the primary effect of insulin is rapid inhibition of transcription. On the other hand, cortisol, glucagon, and cAMP stimulate IGFBP-1 production. Limited data also show a potent stimulatory effect of phorbol esters. A detailed review of IGFBP-1 levels and physiology in vivo and in vitro is presented. The function of IGFBP-1 is not completely defined. However, several studies demonstrate that IGFBP-1 inhibits IGF binding to cell surface receptors and thereby inhibits IGF-mediated mitogenic and cell metabolic actions. Furthermore, IGFBP-1 regulation by insulin and glucoregulatory hormones in vitro and limited in vivo data are consistent with a role for IGFBP-1 in glucose counterregulation.
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PMID:Regulation and function of insulin-like growth factor-binding protein-1. 769 Apr 86

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

An anabolic stimulus is needed in addition to conventional nutritional support in the catabolic "flow" phase of severe trauma. One promising therapy appears to be rhGH infusion which has direct as well as hormonal mediated substrate effects. We investigated on a whole-body level, the basic metabolic effects of trauma within 48-60 h after injury in 20 severely injured (injury severity score [ISS] = 31 +/- 2), highly catabolic (N loss = 19 +/- 2 g/d), hypermetabolic (resting energy expenditure [REE] = 141 +/- 5% basal energy expenditure [BEE]), adult (age 46 +/- 5 y) multiple-trauma victims, before starting nutrition therapy and its modification after 1 wk of rhGH supplementation with TPN (1.1 x REE calories, 250 mg N.kg-1.d-1). Group H (n = 10) randomly received at 8:00 a.m. on a daily basis rhGH (0.15 mg.kg-1.d-1) and Group C (n = 10) received the vehicle of infusion. Protein metabolism (turnover, synthesis and breakdown rates, and N balance); glucose kinetics (production, oxidation, and recycling); lipid metabolism, (lipolysis and fat oxidation rates), daily metabolic and fuel substrate oxidation rate (indirect calorimetry); and plasma levels of hormones, substrates, and amino acids were quantified. In group H compared to group C: N balance is less negative (-41 +/- 18 vs -121 +/- 19 mg N.kg-1.d-1, P = 0.001); whole body protein synthesis rate is 28 +/- 2% (P = 0.05) higher; protein synthesis efficiency is higher (62 +/- 2% vs 48 +/- 3%, P = 0.010); plasma glucose level is significantly elevated (256 +/- 25 vs 202 +/- 17 mg/dL, P = 0.05) without affecting hepatic glucose output (1.51 +/- 0.20 vs 1.56 +/- 0.6 mg N.kg-1.min-1), glucose oxidation and recycling rates; significantly enhanced rate of lipolysis (P = 0.006) and free fatty acid reesterification (P = 0.05); significantly elevated plasma levels of anabolic GH, IGF-1, IGFBP-3, and insulin; trauma induced counter-regulatory hormone (cortisol, glucagon, catecholamines) levels are not altered; trauma induced hypoaminoacidemia is normalized (P < 0.05) and 3-methylhistidine excretion is significantly low (P < 0.001). Improved plasma IGF-1 levels in Group H compared with Group C account for protein anabolic effects of adjuvant rhGH and may be helpful in promoting tissue repair and early recovery. Skeletal muscle protein is spared by rhGH resulting in the stimulation of visceral protein breakdown. The hyperglycemic, hyperinsulinemia observed during rhGH supplementation may be due to defective nonoxidative glucose disposal, as well as inhibition of glucose transport activity into tissue cells. The simultaneous operation of increased lipolytic and reesterification processes may allow the adipocyte to respond rapidly to changes in peripheral metabolic fuel requirements during injury. This integral approach helps us to better understand the mechanism of the metabolic effects of rhGH.
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PMID:Integrated nutritional, hormonal, and metabolic effects of recombinant human growth hormone (rhGH) supplementation in trauma patients. 897 4

The effect of body condition per se on plasma IGFs and IGF-binding proteins (IGFBPs) and the whole-body metabolic responses to recombinant DNA-derived bovine GH (rbGH) in both the fed and the fasted state were determined in lean and dietary obese sheep (n = 6/group). Sheep at zero-energy balance and equilibrium body weight were injected s.c. for 12 days with 100 micrograms/kg rbGH immediately before their morning feeding. Before GH treatment, fasting plasma concentrations of insulin (17.0 +/- 1.9 vs 7.5 +/- 0.7 microU/ml), IGF-I (345 +/- 25 vs 248 +/- 10 ng/ml), glucose (52.6 +/- 1.1 vs 48.3 +/- 0.7 mg/dl), and free fatty acid (FFA) (355 +/- 45 vs 229 +/- 24 nmol/ml) were greater (P < 0.05) and those of GH (1.1 +/- 0.2 vs 2.6 +/- 0.3 ng/ml) were lower (P < 0.05) in obese than in lean sheep. Fasting concentrations of IGF-II and glucagon were not affected (P > 0.05) by obesity. GH concentrations were increased equivalently by 6-9 ng/ml in lean and obese sheep during GH treatment. GH caused an immediate and a marked fivefold increase in the fasting insulin level in obese sheep but only minimally affected insulin concentration in lean sheep. The increment in fasting glucose during GH treatment was greater (P < 0.05) in obese (8-12 mg/dl) than in lean (2-5 mg/dl) sheep. Frequent measurements in the first 8 h after feeding and injection of excipient (day 0) or the first (day 1) sixth (day 6) and twelfth (day 12) daily injection of GH showed that prandial metabolism in both groups of sheep was affected minimally by GH. However, GH treatment on day 1 (not days 6 or 12) acutely attenuated the feeding-induced suppression of plasma FFA in both groups of sheep and this effect was significantly greater in obese than in lean sheep. Although obese sheep were hyposomatotropic, the basal and GH-induced increases in plasma IGF-I concentrations were greater (P < 0.05) in obese than in lean sheep. Plasma IGF-II was unaffected by obesity and was not increased by GH stimulation. Western ligand blotting showed that IGFBP-3 accounted for approximately 50-60% of the plasma IGF-I binding capacity in sheep respectively both before and during GH treatment. Basal plasma levels of IGFBP-2 were lower (P < 0.05) and those of IGFBP-3 greater (P < 0.05) in obese compared with lean sheep. GH increased the level of IGFBP-3 equally in lean and obese sheep, but suppressed the expression of IGFBP-2 more (P < 0.05) in lean than in obese sheep. We concluded that the diabetogenic-like actions of GH in sheep were exaggerated markedly by obesity, and were expressed more during the fasted than the fed states. The effects of GH stimulation on the endocrine pancreas may be selective for beta-cells and preferentially enhanced by obesity. GH regulation of IGF-I and the IGFBPs differs in lean and obese sheep.
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PMID:Differential effects of GH stimulation on fasting and prandial metabolism and plasma IGFs and IGF-binding proteins in lean and obese sheep. 929 44

We studied the effects of continuous subcutaneous infusion of octreotide (100 micrograms/day for 5 days) on glycaemic values, counterregulatory hormones secretion, hepatic glucose production (HGP) and glucose disposal during an euglycaemic clamp in 7 C-peptide-negative type 1 diabetic patients and 7 C-peptide positive insulin-treated type 2 diabetic patients. In type 1, but not type 2 diabetic patients, octreotide significantly reduced glycaemic values (P < 0.005) and also diminished HGP during an euglycaemic clamp (P < 0.05). However, insulin stimulated global glucose uptake remained unchanged. GH, glucagon, IGF-I, IGFBP-3 levels, were significantly lowered by octreotide in both type 1 and type 2 diabetic patients whereas cortisol and epinephrine remained unmodified. Moreover in type 2 diabetic patients both basal (P < 0.05) and after-meal (P < 0.01) C-peptide secretion was reduced by octreotide. These data point to different metabolic effects of octreotide in type 1 versus type 2 diabetic patients with the drug only being able to reduce glycaemic values and HGP in the former but not in the latter subjects. The failure of octreotide to diminish glycaemic values and HGP in type 2 diabetic patients in spite of its ability to lower GH and glucagon may probably depend on temporary blockage of residual endogenous insulin secretion induced by octreotide administration.
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PMID:Effects of octreotide on glycaemic control, glucose disposal, hepatic glucose production and counterregulatory hormones secretion in type 1 and type 2 insulin treated diabetic patients. 948 71

The purpose of the study was to investigate the effects of octreotide on the response of counterregulatory hormones to insulin-induced hypoglycaemia in 9 Type 1 diabetic patients without autonomic neuropathy. During an euglycaemic clamp, saline or octreotide (50 mcg) was randomly injected subcutaneously. Patients were then clamped to hypoglycaemic levels (2.5 mmol/l), and hormonal response was evaluated after 30 min of hypoglycaemia. Although octreotide suppressed both GH (0.5 +/- 0.01 vs 9.5 +/- 0.9 ng/ml, p < 0.001) and glucagon (110 +/- 9 vs 165 +/- 10 pg/ml, p < 0.05) responses, it did not affect cortisol, epinephrine, IGF-1 and IGFBP-3 levels. The time required for recovery from hypoglycaemia was longer after octreotide (19.1 +/- 1.2 min vs 14.3 +/- 0.9 min, p < 0.05), and a greater amount of infused glucose was needed to reach normoglycaemia (g 24.6 +/- 1.2 vs 17.7 +/- 1.3, p < 0.05). These findings suggest that administration of octreotide to insulin-treated Type 1 diabetic patients may impair anti-hypoglycaemic counterregulatory mechanisms through suppression of glucagon and GH responses.
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PMID:Effect of octreotide on growth hormone, IGF-I, IGFBP-3, glucagon, cortisol and epinephrine response to insulin-induced hypoglycaemia in insulin-dependent diabetic patients. 949 59

Growth failure and anterior pituitary dysfunction are clinical features of the CHARGE and VATER associations. This study investigated pituitary dysfunction as a potential cause of poor growth in a series of four and three patients with the CHARGE and VATER associations, respectively, who had height standard deviation scores (SDS) less than-2. Five of the seven patients had associated subnormal growth velocity SDS. Patients were investigated with a combination of dynamic and basal endocrine tests. All patients were found to be normonatraemic and to have normal basal thyrotroph and stimulated corticotroph function. The one peripubertal patient had evidence of biochemical gonadotroph dysfunction. Although two patients had marginally low stimulated serum growth hormone responses to glucagon stimulation testing, this was associated with either normal growth velocity or normal serum insulin-like growth factor binding protein 3 (IGFBP-3) concentrations. Thus, somatotroph dysfunction could not be demonstrated unequivocally in any patient. Poor childhood linear growth in the CHARGE and VATER associations does not appear to be associated with pituitary dysfunction.
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PMID:Growth failure and pituitary function in CHARGE and VATER associations. 1032 34

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