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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of acute administration of human recombinant insulin-like growth factor-I (rhIGF-I) on amino acid (AA) flux between hindlimbs, liver and gut were investigated in anaesthetized post-operative dogs. rhIGF-I produced about a 10-fold increase in plasma IGF-I concentrations above baseline values (P < 0.001), increased the plasma levels of glucagon and adrenaline (P < 0.05), and evoked a fall in plasma glucose (-55 +/- 8%; (P < 0.001) and plasma total AA levels (-23 +/- 8%; P < 0.05). AA flux in post-absorptive dogs under NaCl infusions was characterized by an efflux of AA from the hindlimbs (as a result of the protein-catabolic situation), an equal AA balance across the gut and an AA uptake by the liver. The administration of rhIGF-I increased hepatic AA uptake in the NaCl group from 3.51 +/- 0.8 to 7.5 +/- 0.4 mumol/min per kg (P < 0.01) and in the AA-infused group from 16.8 +/- 0.6 to 22.4 +/- 1.5 mumol/min per kg (P < 0.05), but did not influence the AA balance across hindlimbs and gut. Glucose infusions normalized the plasma concentrations of counter-regulatory hormones without influencing the inter-organ AA balances. We conclude that hypoaminoacidaemia caused by rhIGF-I infusions is the result of a stimulated AA uptake by the liver, but is unrelated to alterations of AA exchange across the hindlimbs.
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PMID:Acute effects of insulin-like growth factor I on inter-organ amino acid flux in protein-catabolic dogs. 828 75

Previous in vivo and in vitro studies indicate that insulin is required in adult newt forelimb regeneration. The objectives of the current study were 1) to detect insulin receptors in the liver (a classical target organ for insulin) and once verified, detection of insulin receptors in the adult newt forelimb regenerate; and 2) to determine whether locally implanting insulin antibody-soaked hydrolyzed polyacrylamide beads (hypa beads) into a regenerating forelimb blastema would affect its growth and/or differentiation. The results show that insulin receptors are detectable in the plasma membranes of newt liver and forelimb regenerates. Radioiodinated bovine insulin binding is time-dependent and specific; unlabeled bovine insulin competes with labeled insulin for binding to NLPM more effectively than does insulin-like growth factor-I, guinea pig insulin, and glucagon. The newt hepatic insulin receptor binds insulin with high affinity (1.1 nM-1) and low capacity (63 +/- 8 fmoles/mg). The size of the alpha subunit of the newt insulin receptor is 130 kDA and that of the beta subunit is 95 kDa. The beta subunits undergo insulin-stimulated phosphorylation in response to insulin. An autoantibody against the human insulin receptor recognizes the newt receptor protein. Insulin receptors are also detectable in 15 and 20 day newt forelimb regenerates. Specific immunogold labelling of the receptor-bound antibody appears to be restricted to the cellular processes of the regenerate. Implanting hypa beads soaked with purified insulin antibody into regenerating adult newt forelimbs results in abnormal growth and differentiation of the regenerates, confirming that insulin plays an essential role in adult newt forelimb regeneration.
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PMID:Detection of insulin receptors in newt liver and forelimb regenerates and the effects of local insulin deprivation on epimorphic regeneration. 835 93

Sucrose density centrifugation was used to prepare a partially purified membrane fraction from the mammary glands of non-pregnant, pregnant and lactating sheep. The binding of 125I-labelled insulin-like growth factor-I (IGF-I) was dependent on membrane protein concentration, pH, time and temperature. The binding showed the characteristics of a type-1 IGF receptor, being displaced by IGF-I (median effective dose (ED50) 0.55 nmol/l), less effectively by IGF-II (ED50 8.8 nmol/l) and least effectively by insulin. Glucagon, ovine prolactin and ovine placental lactogen could not displace binding. A molecular weight of 135,000 was determined by affinity cross-linking using disuccinimidyl suberate; this was consistent with the reported size of the type-1 receptor alpha-subunit. Scatchard analysis was used to determine binding affinity and numbers of IGF-I-binding sites. A single class of high-affinity binding sites was found in all physiological states. In non-pregnant sheep and sheep at days 40, 75 and 110-120 of pregnancy and at term, the binding affinity was similar (apparent dissociation constant (Kd) 2.73 +/- 0.31 nmol/l, n = 22). In lactating sheep (weeks 1, 4 and 10), the binding affinity was significantly (P = 0.02) higher (Kd 0.77 +/- 0.06 nmol/l n = 9). Binding capacity was similar in non-pregnant and pregnant sheep (1005 +/- 113 fmol/mg, n = 19), but fell by parturition and remained low in lactation (570 +/- 52 fmol/mg membrane protein, n = 12). The results suggest that the mammary growth of pregnancy is not regulated at the level of the type-1 IGF receptor.
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PMID:Receptor binding of insulin-like growth factor-I to mammary microsomes from non-pregnant, pregnant and lactating sheep. 845 95

Seven children, with a mean (SD) age of 4.6 (2.1) years, who as infants (21 (7.5) days) underwent near total (95-98%) pancreatectomy for persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) were studied. At birth all the infants were macrosomic. Four infants had been born after a difficult labour, of whom three had moderate birth asphyxia and respiratory distress. All had normal thyroid function. After surgery transient hyperglycaemia was manifest in six of the children and required insulin treatment for 5.8 (3.8) weeks, and transient hypoglycaemia was encountered in one child and responded well to increased carbohydrate intake and diazoxide for three weeks. Six of the children rapidly crossed down their length and weight centiles during the first year after surgery. At the end of the first year these children were at or below the 5th centile of height and weight for their age and gender. After a period of 4.6 (2.1) years, their mean (SD) height score was -2.57 (0.5), growth velocity 3.9 (0.75) cm/year, and growth velocity SD score -2.1 (0.55)l these were significantly low and denoted significant growth retardation. The growth hormone peak responses to provocation with clonidine were normal (13.5 (2.8) micrograms/l). However, the circulating insulin-like growth factor-I (IGF-I) concentrations were significantly decreased (79 (34) ng/ml). Three of the children developed diabetes at two and a half, five, and seven years after surgery, two others had impaired oral glucose tolerance and six out of the seven children had an impaired C peptide response to glucagon. Defective insulin secretion in these children might directly inhibit IGF-I synthesis in the liver. The body mass index of the pancreatectomised children was 14.9 (0.5) and was normal for age and gender; they had a normal 72 hour faecal fat content and normal serum albumin concentration. These data indicated grossly adequate exocrine pancreatic function. It appears that children requiring near total pancreatectomy for PHHI have normal developmental milestones but defective linear growth with impaired insulin secretion and low IGF-I production despite normal growth hormone response to provocation.
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PMID:Growth and endocrine function after near total pancreatectomy for hyperinsulinaemic hypoglycaemia. 866 50

We have previously reported fasting hyperglycaemia, hyperinsulinaemia, and glucose intolerance in transgenic (Tg) mice which overexpress rat insulin-like growth factor binding protein-1 (IGFBP-1). An increase in pancreatic islet size and number was also observed in this model. Islets from Tg mice had relatively more beta cells and less alpha cells than islets from wild-type (Wt) mice. These observations prompted us to investigate the effects of glucose and insulin-like growth factor-I (IGF-I) on insulin and glucagon release by isolated islets from Tg and Wt mice. Under basal glucose conditions, islets from Tg mice released significantly more insulin and less glucagon than islets from Wt mice. This difference was significant even when corrected for the increased size and cellularity of islets from Tg mice. A dose-dependent increase in insulin release was observed with increased glucose concentrations in both Wt and Tg mice. At all but the highest glucose concentration, islets from Tg mice released significantly greater amounts of insulin than islets from Wt mice. Addition of IGF-I to islet incubations resulted in a dose-dependent increase in insulin release. However, the effect of IGF-I on islets from Tg mice was reduced compared to islets from Wt mice. From these data we conclude that IGF-I stimulates rather than inhibits insulin secretion in isolated murine islets. Furthermore, an intrinsic defect in pancreatic islet insulin release is not responsible for the glucose intolerance in Tg mice. Rather, the data suggest that the hyperglycaemia or local effects of IGFBP-1 over-expression results in a state of enhanced insulin secretion which persists under short-term in vitro culture conditions.
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PMID:Effects of insulin-like growth factors (IGF) on pancreatic islet function in IGF binding protein-1 transgenic mice. 893 88

Hypertransfusion therapy has dramatically increased the duration and quality of life in patients with B-thalassemia major; however, it leads to chronic iron overload, and is frequently complicated by the development of diabetes mellitus or impaired glucose tolerance. To determine the early effect of iron overload on the endocrine pancreatic function, we studied glucose, insulin, and glucagon responses to oral load of glucose and to arginine provocation in 15 children with B-thalassemia major, before and after (3.1 +/- 0.6 years) high-transfusion and iron chelation and compared them with 15 age matched normal controls. In addition, we evaluated growth hormone (GH) responses to oral clonidine and measured the circulating insulin-like growth factor-I concentration in thalassemic children on long-term transfusion and controls. After long-term high-transfusion, thalassemic children had significantly decreased serum insulin concentrations and low insulin/glucose ratios at 60 and 120 min after an oral glucose load (1.75 g/kg) in comparison with values before therapy and those for controls. None of the thalassemic children had glucose intolerance after this period of frequent blood transfusion; however, their serum glucose levels at 60 and 120 min after the oral glucose load were significantly higher compared to control children. Thirty minutes after starting arginine infusion, serum insulin concentration was significantly lower in thalassemic children compared to before therapy. Basal and arginine-stimulated glucagon secretions were significantly elevated in thalassemic children on long-term blood transfusion with significantly low serum insulin/glucagon ratios. In addition, the high basal serum glucagon concentrations were not suppressed after the oral glucose load. Despite hyperglucagonaemia in all thalassemic children, their blood glucose dropped appropriately below 50 per cent of the fasting glucose level after an intravenous insulin dose (0.1 U/kg) ruling out any significant insulin-resistance. GH responses to clonidine provocation were subnormal in thalassemic children after long-term blood transfusion compared to controls. In summary, thalassemic children on long-term blood transfusion and iron chelation have progressive and early loss of B-cell mass, manifested by decreased insulin release in response to secretagogues, before the development of significant insulin resistance or impairment of glucose tolerance.
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PMID:Insulin and glucagon responses to provocation with glucose and arginine in prepubertal children with thalassemia major before and after long-term blood transfusion. 893 61

Local vascular expression and action of insulin-like growth factor-I (IGF-I) appear to be important in the biologic events that follow arterial wall injury. Octreotide, a long-acting somatostatin analog, is a potent inhibitor of the growth hormone/IGF-I axis. We examined the effects of octreotide on the vascular IGF-I and IGF-binding proteins (IGFBP), gene regulation, smooth muscle cell proliferation, and neointimal thickening after arterial wall injury. Treatment with octreotide selectively decreased IGF-I mRNA expression in normal rat arteries by 70% and prevented the induction of the IGF-I gene after balloon injury. Because up-regulation of platelet-derived growth factor-A gene was not affected, and because there was no change in plasma growth hormone, IGF-I, and glucagon levels, it appears that this effect is selective and mediated locally. Of the IGFBP, IGFBP-4 was modestly up-regulated after balloon injury, whereas treatment with octreotide had no effect on IGFBP-4 expression. The inhibitory effects of octreotide on vascular IGF-I were associated with a decrease in the number of proliferating cell nuclear antigen-positive cells and an up to 90% reduction in neointimal thickening after balloon injury in a dose-dependent fashion.
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PMID:Direct effects of somatostatin analog octreotide on insulin-like growth factor-I in the arterial wall. 912 Nov 16

Impaired growth involving both height and weight accompanying sickle cell disease (SCD) poses diagnostic and therapeutic problems. We undertook this study to test the hypothesis that this impaired growth is associated with abnormalities of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF binding protein-3 (IGFBP-3) axis in 21 children with SCD and that SCD is associated with GH resistance. Nine of 21 children with SCD had a defective GH response to both clonidine and glucagon provocation (peak < 10 micrograms/L); these children differed from the 12 others in having slower linear growth velocity (GV and GVSDS), lower circulating concentrations of IGF-I and IGFBP-3, and either partial or complete empty sellae in computed tomographic scans of the hypothalamic-pituitary area. In this group of patients with SCD, it appears that defective GH secretion and consequent low IGF-I production are the major etiological factors causing the slow growth. The two groups with SCD did not differ significantly in dietary intake, body mass index (BMI), midarm circumferences, skinfold thickness, serum albumin concentration, or intestinal absorption of D-xylose. A single injection of GH produced a smaller increase in circulating IGF-I in children with SCD with or without defective GH secretion versus 10 age-matched children with idiopathic short stature (ISS) and 11 children with isolated GH deficiency (GHD), suggesting partial GH resistance in the SCD group. The presence of defective GH secretion, decreased IGF-I synthesis, and partial resistance to GH in short children with SCD suggests that treatment with IGF-I may be superior to GH therapy for improving growth.
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PMID:Growth hormone secretion and circulating insulin-like growth factor-I (IGF-I) and IGF binding protein-3 concentrations in children with sickle cell disease. 936 79

Hyperinsulinemic, normoglycemic clamps were performed before and after 24 h of either hypocaloric nutrition or bed rest in healthy subjects. Decreased insulin sensitivity and insulin-like growth factor-I (IGF-I) bioavalibility, as measured by the serum IGF-I/insulin-like growth factor binding protein-1 (IGFBP-1) ratio, was found after fasting, whereas no metabolic changes were found after bed rest. Glucagon seems to be a key regulator of IGFBP-1 after brief hypocaloric nutrition. Hypocaloric nutrition and immobilization may add to the catabolic response to surgery and other trauma. Presently, six healthy subjects were studied before and after a 24-h period of hypocaloric nutrition (200 kcal/24 h, fast) or immobilization (bed rest) using the hyperinsulinemic (0.8 mU.kg-1.min-1), normoglycemic (4.5 mmol/L) clamp, indirect calorimetry, and circulating levels of substrates and hormones. After fast, body weight decreased (P < 0.05), and nitrogen balance was negative (-10 +/- 1 g urea nitrogen/24 h). Basal levels of free fatty acids, glucagon, and IGFBP-1 increased (P < 0.05), whereas c-peptide levels and the IGF-I/IGFBP-1 ratio decreased (P < 0.05). However, no change was found in basal levels of IGF-1 or substrate oxidation. Furthermore, changes (%) in basal levels of glucagon after fast correlated to IGFBP-1 (r = 1.0, P < 0.05), whereas the suppressibility of IGFBP-1 by insulin was maintained at normal levels. During clamps, glucose infusion rates (GIR) decreased after fast (-43 +/- 13%, mean +/- SEM, P < 0.001). Although not significantly, clamp levels of fat oxidation tended to increase and glucose oxidation tended to decrease. Levels of IGFBP-1 during clamps were higher as compared with the control clamp (P < 0.05). No adverse metabolic changes were seen after bed rest, and no change in GIR during clamps were seen as compared with the control measurement (0 +/- 14%). After brief hypocaloric nutrition, insulin sensitivity is reduced, whereas IGF-I bioavalibility is reduced by an increase in levels of IGFBP-1. Glucagon seems to contribute to the increase in IGFBP-1 during these conditions.
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PMID:Short-term hypocaloric nutrition but not bed rest decrease insulin sensitivity and IGF-I bioavailability in healthy subjects: the importance of glucagon. 943 9

To investigate whether recombinant human insulin-like growth factor-I (rhIGF-I) has direct effects on the insulin requirement to maintain euglycemia independent of the growth hormone (GH) level, nine subjects with insulin-dependent diabetes mellitus ([IDDM] seven females; median (range) age, duration of diabetes, and hemoglobin A1C [HbA1C], 16.9 (12.5 to 21.9) years, 11.8 (4.6 to 16.8) years, and 9.8% (7.9% to 14.1%), respectively) underwent two euglycemic studies (6:00 PM to 8:00 AM) after double-blind subcutaneous administration of rhIGF-I/placebo (40 microg/kg). Octreotide infusion (300 ng/kg/h) suppressed endogenous GH, and three identical discrete GH pulses were infused on both nights. Variable-rate insulin infusion maintained euglycemia. Samples were taken every 15 minutes (glucose and GH), 30 minutes (insulin and intermediate metabolites), and 60 minutes (IGF-I and nonesterified fatty acids [NEFA]). Variables were analyzed during the steady-state period of euglycemia (4:00 to 8:00 AM). Data are expressed as the mean +/- SEM. The insulin infusion rate and free-insulin level were both significantly reduced after rhIGF-I administration (0.13 +/- 0.03 v placebo 0.23 +/- 0.05 mU/kg/min, P = .04, and 8.4 +/- 1.3 v placebo 12.1 +/- 1.4 mU/L, P = .03, respectively). GH pulse-related changes in the insulin requirement observed after placebo were not present after rhIGF-I. Glucagon levels were equally suppressed on both nights. Insulin clearance was not altered after rhIGF-I administration. NEFA and ketone levels also were not different on the 2 nights. In conclusion, in adolescents and young adults with diabetes, rhIGF-I administration directly affected insulin requirements independent of GH levels, but had no effect on fatty acid or ketone levels. This difference is related to the abolition of changes in the insulin requirement after GH pulses, and would suggest a complex interaction between GH and IGF-I on insulin action.
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PMID:Recombinant human insulin-like growth factor-I abolishes changes in insulin requirements consequent upon growth hormone pulsatility in young adults with type I diabetes mellitus. 944 Apr 74


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