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)

A series of experiments using isolated rat hepatocytes was carried out to establish rat liver cells in suspension as a physiological model for examining GH responses, and to determine whether acute recombinant bovine GH (rbGH) treatment of rat liver cells increased glucose output and/or suppressed fatty acid synthesis from lactate. Rat liver cells were isolated by collagenase perfusion and incubated in short-term (less than 60 min) suspension. The amount of insulin, glucagon or vasopressin required to elicit a half-maximal response was within the physiological range of the circulating hormone. When hepatocytes from normal rats were acutely (less than 60 min) treated with 0, 0.1, 10, 100 or 1000 nmol rbGH/l, rates of hepatocyte glucose output and fatty acid synthesis were unaltered. In addition, acute rbGH treatment (1000 nmol/l) did not alter hepatocyte responsiveness to insulin or vasopressin. However, acute rbGH treatment of hepatocytes isolated from hypophysectomized rats significantly (P less than 0.05) increased the rate of glucose output twofold and moderately (P less than 0.10) enhanced fatty acid synthesis. The accelerated rate of glucose production was not accompanied by an increase in the amount of glycogen phosphorylase-a. The observations with liver cells from hypophysectomized rats are not consistent with a GH receptor-transducing mechanism which is like that for glucagon (adenylate cyclase-linked) or insulin (tyrosine kinase-linked).
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PMID:Growth hormone acutely increases glucose output by hepatocytes isolated from hypophysectomized rats. 267 Dec 41

Genotypic and phenotypic heterogeneity in patients with growth hormone (GH) insensitivity syndrome suggests that partial defects exist in the GH receptor. The insulin-like growth factor I (IGF-I) generation test was assessed as a means of identifying partial GH receptor defects in a heterogeneous group of 22 prepubertal children with short stature. In a subgroup of nine patients with peak GH levels of 63.7 +/- 3.7 mU/l during a glucagon tolerance test, the response to the IGF-I generation test was no different from that for the group as a whole (peak GH, 43.3 +/- 4.5 mU/l), despite the fact that this subgroup exhibited a negative relationship between height SDS and peak GH and a positive relationship between height SDS and IGF binding protein-3. This preliminary study therefore suggests that the IGF-I generation test in its present form will not be useful as a primary screening test for partial GH insensitivity. Despite this, the IGF-I generation test has been extremely useful in the confirmation of the diagnosis of GHIS and may therefore also prove useful in the confirmation of partial defects in the GH receptor. A subgroup of short children with peak GH levels above 40 mU/l had some characteristics of partial GH receptor deficiency. These children, to whom GH therapy would not normally be given, may respond better to recombinant human IGF-I.
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PMID:The insulin-like growth factor I generation test in the investigation of short stature. 794 97

Liver production of insulin-like growth factor-I (IGF-I) is a major point of control in the growth hormone (GH)/IGF axis, the endocrine system regulating body growth in fishes and other vertebrates. Pituitary GH stimulates hepatocyte production of IGF-I; however, in catabolic states, hepatocyte GH resistance results in decreases in liver IGF-I production. To investigate endocrine mechanisms leading to the development of hepatocyte GH resistance, we examined the regulation of IGF-I mRNA level by GH and metabolic hormones in primary culture of salmon hepatocytes. Cells were cultured in RPMI medium, and exposed to insulin (Ins, 10(-6) M), glucagon (Glu, 10(-6) M), triiodothyronine (T3, 10(-7) M), dexamethasone (Dex, 10(-6) M) and glucagon-like peptide (GLP, 10(-6) M), in the presence and absence of GH (5 x 10(-9) M). GH always increased IGF-I mRNA. None of the other hormones tested alone affected IGF-I mRNA. However, Dex, Ins and Glu reduced the response to GH. The response to GH was inhibited by Dex at concentrations of 10(-12) M and above, by Ins at 10(-9) M and above, and by Glu only at 10(-6) M. Inhibition of GH response by glucocorticoids is found in other vertebrates. Salmon hepatocytes were very sensitive to Dex, suggesting that glucocorticoids may play an important role in salmon growth regulation even in unstressed conditions. Inhibition of GH response by Ins is the opposite of what is found in mammals and chickens, suggesting that the role of Ins in growth regulation may differ between fishes and tetrapods. To examine mechanisms for modulation of GH sensitivity, we measured hepatocyte GH receptor (GHR) mRNA levels. Ins inhibited and Dex stimulated GHR mRNA, suggesting that different mechanisms mediate the inhibition of GH response by these hormones. This study shows that glucocorticoids, Ins, and Glu induce GH resistance in cultured salmon hepatocytes.
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PMID:Metabolic hormones modulate the effect of growth hormone (GH) on insulin-like growth factor-I (IGF-I) mRNA level in primary culture of salmon hepatocytes. 1568 42

Perturbations in endocrine functions can impact normal growth. Endocrine traits were studied in three dwarf calves exhibiting retarded but proportionate growth and four phenotypically normal half-siblings, sired by the same bull, and four unrelated control calves. Plasma 3,5,3'-triiodothyronine and thyroxine concentrations in dwarfs and half-siblings were in the physiological range and responded normally to injected thyroid-releasing hormone. Plasma glucagon concentrations were different (dwarfs, controls>half-siblings; P<0.05). Plasma growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin concentrations in the three groups during an 8-h period were similar, but integrated GH concentrations (areas under concentration curves) were different (dwarfs>controls, P<0.02; half-siblings>controls, P=0.08). Responses of GH to xylazine and to a GH-releasing-factor analogue were similar in dwarfs and half-siblings. Relative gene expression of IGF-1, IGF-2, GH receptor (GHR), insulin receptor, IGF-1 type-1 and -2 receptors (IGF-1R, IGF-2R), and IGF binding proteins were measured in liver and anconeus muscle. GHR mRNA levels were different in liver (dwarfs<controls, P<0.002; dwarfs<half-siblings, P=0.06; half-siblings<controls, P=0.08) but not in muscle. IGF-1R mRNA abundance in liver in half-siblings and controls was 2.4- and 2.5-fold higher (P=0.003 and P=0.001, respectively) and in muscle tissue was 2.3- and 1.8-fold higher (P=0.01 and P=0.08, respectively) than in dwarfs. Hepatic IGF-1R protein levels (Western blots) in muscle were 2.5-fold higher (P<0.05) and in liver and muscle (quantitative immunohistochemistry) were higher (P<0.02 and P<0.07, respectively) in half-siblings than in dwarfs. The reduced presence of IGF-1R may have been the underlying cause of dwarfism in studied calves.
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PMID:Insulin-like growth factor type-1 receptor down-regulation associated with dwarfism in Holstein calves. 1682 14

Laron-type dwarfism is an autosomal recessive disorder caused by deletions or mutations of the growth hormone receptor gene. It is characterized by high circulating levels of growth hormone (GH) and low levels of insulin-like growth factor I (IGF-I). Patients are refractory to both endogenous and exogenous GH, and present severe growth retardation and obesity. Therapy with recombinant human insulin-like growth factor-I (rhIGF-I) accelerates linear growth. We describe a 2-year old girl with Laron syndrome, who presented with postnatal growth failure and hypoglycaemic seizures. Her evaluation disclosed high GH values during a glucagon test (peak GH value 170 ng/ml) and very low IGF I value (0.1 ng/ml) with no rise following GH administration. The growth velocity improved considerably with the administration of IGF I. Molecular analysis showed a heterozygous mutation on exon 4 of the GH receptor gene, inherited from the mother, a rather puzzling finding considering the clinical findings in mother and infant. This case constitutes the first report of Laron syndrome from Greece.
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PMID:Laron syndrome. First report from Greece. 1700 11

Birds have rapid pre- and post-hatching growth rates. The major hormones required to support normal growth are growth hormone (GH), triiodothyronine (T(3)) and insulin-like growth factor-I (IGF-I). Optimal growth requires a "set-point" concentration of both IGF-I and T(3) in the circulation. Pituitary GH plays a role in controlling the circulating concentrations of both IGF-I and T(3). Nutritional restriction (energy, protein) leads to reductions in circulating concentrations of both IGF-I and T(3) with increased GH secretion due removal of negative feedback. Similarly, there is un-coupling of the GH-IGF-I axis in stunting disease. A critical control point is at the level of the liver and GH receptor/signal transduction. The major hormones controlling metabolism include glucagon, insulin, adrenal glucocorticoid hormone, corticosterone and potentially somatostatin. Chickens and turkeys have higher circulating concentrations of glucose than those of livestock mammals. What are not known include the following: the biological basis for the high basal glucose concentrations; the quantitative fluxes of key metabolites in the fed and fasted state through growth and development; the relative contribution of different organs to gluconeogenesis; the relative importance of insulin and somatostatin in controlling lipolysis and the role of gastro-intestinal hormones in the control of metabolism.
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PMID:Perspectives on the endocrinology of poultry growth and metabolism. 1939 57