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)

Hyperglycaemia in diabetes results from a combination of increased hepatic glucose production and decreased metabolic clearance of glucose. Our report summarizes recent work conducted in our laboratory to investigate the regulatory factors involved in the control of glucose turnover in diabetes. The action of insulin, both directly and indirectly, in regulating glucose turnover in diabetic dogs is considered. 1) In the depancreatized diabetic dog, peripheral rather than portal insulin levels determine the suppression of hepatic glucose production via indirect mechanisms such as limiting, precursors for gluconeogenesis and/or inhibiting glucagon secretion. 2) The differential effects of insulin and insulin-like growth factor I on glucose turnover may be dependent on a decline in glycaemia since previously observed differential effects on glucose turnover were masked under conditions of clamped hyperglycaemia in the depancreatized dog. 3) In a paradoxical dichotomous fashion, hyperglycaemia both contributes to, and compensates for, defective glucose clearance in diabetes. Acute restoration of euglycaemia significantly improves glucose clearance at rest and normalizes the exercise-induced increment in clearance in alloxan-diabetic dogs. 4) Our model of centrally-induced stress also shows that an increase in glucose utilization and clearance is largely independent of changes in insulin and that the combined effects of catecholamines and glucagon are responsible for increasing glucose production.
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PMID:Determinants of glucose turnover in the pathophysiology of diabetes: an in vivo analysis in diabetic dogs. 879 91

Eight healthy subjects were treated with saline or insulin-like growth factor I (IGF-I, 10 micrograms.kg-1.h-1 sc) for 3 days in a crossover randomized fashion. Substrate balances across the forearm skeletal vascular bed were determined in the postabsorptive state and during a hyperinsulinemic euglycemic clamp. In the basal state, net forearm uptake of free fatty acids and ketone bodies was increased during IGF-I administration in the face of elevated plasma levels of these substrates, whereas basal glucose levels and forearm glucose balance were unchanged. However, whole body and net forearm glucose uptakes were more markedly stimulated by insulin (+20 and +8%, respectively) in the IGF-I period. Additionally, counterregulatory hormone responses were examined during insulin-induced stepwise hypoglycemia. Responses of growth hormone and glucagon were blunted, those of cortisol and epinephrine were more marked, and that of norepineprine was unchanged during IGF-I administration. These changes were accompanied with delayed recovery from hypoglycemia.
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PMID:IGF-I alters skeletal muscle substrate metabolism and blunts recovery from insulin-induced hypoglycemia. 892 57

The potential effects of growth hormone (GH) deficiency in adults and the importance of GH secretion in adult life have only been recognized and documented recently. It has been suggested that GH-deficient adults may have premature mortality, abnormalities in body composition and bone density with impaired physical performance and psychological well-being, which are sometimes improved by GH replacement. It is essential, therefore, to establish reliable standards to define GH deficiency in adults. Patients with possible GH deficiency often have primary pituitary or hypothalamic disorders or have undergone surgery or radiotherapy, and thus show evidence of a failure of one of the other pituitary hormones. Several biochemical approaches have been studied to define GH deficiency in the adult and no universal consensus has yet been reached. The most widely established criterion is the peak serum GH concentration achieved during a provocative test, usually the insulin tolerance test (ITT), or following other pharmacological stimuli (e.g. glucagon, arginine, clonidine or GH-releasing factor) but, alternatively, a more physiological stimulus (such as sleep, fasting or exercise) has been used. Spontaneous circulating levels of hormones of the GH axis [24-hour integrated GH concentration, serum insulin-like growth factor I (IGF-I) or IGF-binding protein-3] have been used in the diagnosis of childhood GH deficiency. They have been tested in adults as well but seem to have a more limited role. There are several factors complicating the evaluation of these results. Basal and stimulated GH and IGF-I levels decline with age and with obesity, levels tend to be higher in females and are dependent on nutritional and physical status. The ITT potentially has some risk attached, e.g. in the presence of ischaemic heart disease, but it has proved to be safe in general when used in specialized departments. Other tests are less reliable; releasing hormone tests only assess the readily releasable stores within the pituitary and not the physiological secretory status. The 'cut-off' point for the definition of subnormal responses ideally needs to be set for each provocative test, for each age group, for each degree of obesity and for both sexes. There is considerable variability in GH assays among different laboratories, which makes it difficult to compare hormone levels. The reproducibility of provocative tests can also be variable. An advantage of the hypoglycaemia and glucagon tests is that they allow simultaneous assessment of the adrenocorticotropic hormone reserve.
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PMID:Diagnosis of growth hormone deficiency in adults. 895 Jun 17

Insulin-degrading enzyme (IDE) is a component of a cytosolic complex that includes multicatalytic proteinase (MCP), the major cytoplasmic proteolytic activity. Insulin, the primary substrate for IDE, inhibits the proteolytic activity of the IDE-MCP complex but not of purified MCP. This provides a regulatory role for IDE in cellular proteolysis and a potential mechanism for intracellular insulin action. To examine the specificity and to explore the mechanisms for the IDE-MCP interaction, we studied the functional interaction of a variety of peptides with the complex. Atrial natriuretic peptide (ANP), relaxin, glucagon, proinsulin, and insulin-like growth factor II (IGF-II) bind to and are degraded by IDE. These peptides have significant inhibitory effects on the chymotrypsin-like and trypsin-like MCP catalytic activities but not the peptidyl-glutamyl hydrolyzing activity. A panel of peptides that are not ligands of IDE had no effect. To explore the potential mechanism for the IDE control of MCP activity, dose response curves for insulin-like growth factor I (IGF-I) and IGF-II effects on MCP chymotrypsin-like activity were determined. IGF-II, which (similar to insulin) is a good substrate for IDE, had a substantial inhibitory effect, whereas IGF-I, which is bound but poorly degraded, had little inhibitory activity on MCP. Proinsulin, another ligand of IDE that is tightly bound but poorly degraded, had a partial effect on MCP activity, but inhibited the full insulin effect. These data suggest a requirement for both the binding and degradation of IDE ligands for the full inhibition of MCP. Insulin-sized degradation products, substrates of IDE, also inhibited MCP activity. Further examination of the insulin effect on MCP included kinetic studies. Insulin produced a noncompetitive inhibition of both the chymotrypsin-like and trypsin-like activities of MCP. These data suggest that the insulin-IDE effect on MCP is due to conformational changes in the IDE-MCP complex and provide an intracellular mechanism of action for insulin.
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PMID:Characterization of the insulin inhibition of the peptidolytic activities of the insulin-degrading enzyme-proteasome complex. 900 Jun 94

The ontogeny of endocrine cells and nerve fibers containing immunoreactivities for 12 regulatory peptides and serotonin was studied in the digestive tract of a flatfish, the turbot (Scophthalmus maximus), using antisera specific for mammalian and teleostean hormones. Transient insulin-immunoreactive (-IR) endocrine cells were detected from day 5 to day 10 in stomach and intestine I. Somatostatin (SOM)-IR cells appeared at day 8 in the stomach anlage and intestine I. In contrast to the islet cells, they reacted with antisera against mammalian (m) SOM-14 and salmon (s) SOM-25. Infrequent nerve fibers reacting only with anti-mSOM-14 appeared around day 24. Thus, different forms of SOM seem to be present in the gastro-entero-pancreatic system and the enteric nervous system. Neuropeptide Y (NPY)-, salmon pancreatic polypeptide (sPP)- and mPP-immunoreactivities coexisted throughout development. In entero-endocrine cells, NPY/PP-immunoreactivity was first observed at day 8 and around day 24 in enteric nerve fibers. Glucagon (GLUC)-IR entero-endocrine cells appeared at day 5. No coexistence of NPY/PP- and GLUC-immunoreactivities was observed. The first insulin-like growth factor I (IGF-I)-IR cells were identified around day 8. They seemed to contain none of the other peptides. Their number and distribution exhibited great interindividual differences. Vasoactive intestinal polypeptide (VIP)-IR entero-endocrine cells appeared as late as around day 24. The first VIP-IR nerve fibers, however, were identified at day 5. Infrequent neurotensin (NT)-IR cells appeared along the intestine around day 10 and NT-IR nerve fibers at day 17. The first serotonin (SER)-IR cells were observed in the stomach anlage around day 10 and SER-IR nerve fibers at day 15 throughout the gastro-intestinal tract. Gastrin (GAS)/cholecystokinin (CCK)-IR cells appeared around day 11 in stomach and intestine I. The first substance P (SP)-IR enteric nerve fibers were detected around day 8 and SP-IR endocrine cells at day 11. Pancreastatin (PST)-IR cells were identified in the stomach anlage and intestine I around day 8 and contained NT-, GAS/CCK- and SER-immunoreactivities in coexistence. Thus, several developmental phases can be distinguished: (1) at the onset of exogenous feeding only transient INS-IR cells and VIP-IR nerve fibers are present; (2) a differentiated entero-endocrine system establishes during the early phase of exogenous feeding; (3) before the final differentiation of stomach and gut GAS/CCK-IR cell appear; (4) after metamorphosis most of the different types of regulatory peptide-containing nerve fibers develop, probably setting up the fine regulation of gastro-intestinal blood flow and motility.
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PMID:An immunohistochemical analysis of the ontogeny, distribution and coexistence of 12 regulatory peptides and serotonin in endocrine cells and nerve fibers of the digestive tract of the turbot, Scophthalmus maximus (Teleostei). 900 19

Between 20% and 87% of young adults who had completed growth hormone (GH) therapy in childhood for a putative diagnosis of GH deficiency (GHD) had normal GH responses to provocative tests when they were retested. Patients with isolated idiopathic GHD were more likely to exhibit normal GH responses at retest in young adult life than were patients with multiple pituitary hormone deficits. When determining which patients should receive GH therapy in adult life, those who have isolated GHD should undergo two tests of GH status, while those with multiple anterior pituitary hormone deficits require only one test. Most information is available for the insulin tolerance test, the arginine stimulation test and the glucagon stimulation test, but more recent methods, such as GH-releasing hormone in combination with pyridostigmine, are showing promise in the investigation of GHD. In young adults with childhood-onset GHD, the serum concentration of insulin-like growth factor I is a useful marker of GH status, and can be used in conjunction with a GH provocative test. The choice of GH provocative test should ultimately depend on the experience and policy developed at the centre performing the assessment. Whichever tests are chosen, each should be validated in subjects known to have hypothalamic-pituitary disease as well as in normal individuals.
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PMID:Diagnosis of severe growth hormone (GH) deficiency in young adults who received GH replacement therapy during childhood. 940 59

The control of intestinal epithelial growth is regulated by interactions of growth factors in various cellular compartments of the small and large bowel. Little information is available on the intestinal growth response to combinations of growth factors. We studied the intestinotrophic properties of a dipeptidyl peptidase IV resistant glucagon-like peptide 2 (GLP-2) analog, human [Gly2]GLP-2 (h[Gly2]GLP-2), as well as of epidermal growth factor (EGF), long [Arg3]insulin-like growth factor I (LR3IGF-I), [Gly1]IGF-II, and human growth hormone (hGH), administered by subcutaneous injection alone or in combination in mice. At the doses tested, h[Gly2]GLP-2 was the most potent agent for increasing small and large bowel mass. Mice treated with h[Gly2]GLP-2 and either GH or IGF-I exhibited greater increases in histological parameters of small intestinal growth than did mice treated with h[Gly2]GLP-2 alone. Administration of all five growth factors together induced significant increases in crypt plus villus height and in small and large bowel length and weight. The results of these experiments define regional differences in both the cellular targets and relative activities of intestinotrophic molecules and raise the possibility that selective growth factor combinations may be useful for enhancement of intestinal adaptation in vivo.
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PMID:Intestinal response to growth factors administered alone or in combination with human [Gly2]glucagon-like peptide 2. 943 50

The ontogeny of the classical islet hormones insulin (INS), glucagon (GLUC), somatostatin (SOM), and pancreatic polypeptide (PP) as well as insulin-like growth factor I (IGF-I) in the gastro-entero-pancreatic (GEP) system of Xenopus laevis (stages 41-66) was studied using double immunofluorescence and morphometric analysis. As early as stage 41, clustered INS-immunoreactive (-IR) and isolated GLUC-IR cells occurred in the pancreas. The first SOM-IR cells appeared at stage 43, followed by PP-IR cells at stage 46. About 79% of the PP immunoreactivity was confined to a subpopulation of the GLUC-IR cells. Both the GLUC/PP-IR cells and the PP-IR cells were located in a distinct area of the pancreas. The first islets occurred in premetamorphosis (around stage 50) and comprised mainly INS-IR and GLUC-IR cells. The majority of SOM-IR, PP-IR, and GLUC/PP-IR cells was dispersed. The numbers of hormone cells remained quite constant until the end of prometamorphosis (stage 58). Around stages 60-62, the islets were partly disintegrated and the numbers of islet cells slightly decreased. At stage 63, the cell number began to increase and reached the levels typical for the adult around stage 66. After metamorphic climax, the islets were reformed. In the gastrointestinal tract, transient INS-IR cells occurred prior to the adaptation of the gastrointestinal tract to feeding (stages 41-44) and during metamorphosis when there is remodeling of the gastrointestinal tract (stages 60-63). Therefore, INS released from the transient mucosal INS-IR cells may be involved in the temporary proliferation of mucosal epithelial cells. The first GLUC-IR and SOM-IR cells were seen at stage 41. PP-IR cells followed at stage 46. In contrast to the islets, GLUC-IR and PP-IR cells constituted different cell populations. Around stage 46, the first IGF-I immunoreactions appeared in the GEP-system. In pancreas, IGF-I immunoreactivity was found in the GLUC/PP-IR, cells (85-99%) but was absent from INS-IR, GLUC-IR, and SOM-IR cells. The IGF-I-IR gastro-entero-endocrine cells, however, seemed to contain none of the classical islet hormones.
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PMID:An immunohistochemical and morphometric analysis of insulin, insulin-like growth factor I, glucagon, somatostatin, and PP in the development of the gastro-entero-pancreatic system of Xenopus laevis. 957 Sep 39

Liver fatty acid-binding protein (LFABP) is an abundant protein in hepatocytes that binds most of the long chain fatty acids present in the cytosol. It is suggested to be of importance for fatty acid uptake and utilization in the hepatocyte. In the present study, the effects of bovine GH (bGH) and other hormones on the expression of LFABP and its messenger RNA (mRNA) were studied in hypophysectomized rats and in vitro using primary cultures of rat hepatocytes. One injection of bGH increased LFABP mRNA levels about 5-fold after 6 h, but there was no effect of this treatment on LFABP levels. However, 7 days of bGH treatment increased both LFABP mRNA and LFABP protein levels 2- to 5-fold. Female rats had higher levels of LFABP than male rats. Hypophysectomy of female rats, but not that of male rats, decreased LFABP levels markedly. Treatment of hypophysectomized rats with bGH for 7 days as two daily injections or as a continuous infusion increased LFABP levels to a similar degree. This finding indicates that the sex difference in the expression of LFABP is not regulated by the sexually dimorphic secretory pattern of GH. Neither insulin nor insulin-like growth factor I treatment of hypophysectomized rats for 6-7 days had any effect on LFABP mRNA or LFABP levels. In vitro, bGH dose-dependently increased the expression of LFABP mRNA, but only in the presence of insulin. Insulin alone had a marked dose-dependent effect on LFABP mRNA levels and was of importance for maintaining the expression of LFABP mRNA during the culture. Incubation with bGH increased LFABP mRNA levels within 3 h. GH had no effect on LFABP mRNA levels in the presence of actinomycin D, indicating a transcriptional effect of GH. Incubation with glucagon in vitro decreased LFABP mRNA levels markedly, indicating that glucagon, in contrast to GH, has an effect opposite that of insulin on LFABP mRNA expression. It is concluded that GH is an important regulator of LFABP in vivo and in vitro. In contrast to the effect of GH on insulin-like growth factor I mRNA, the presence of insulin was a prerequisite for the effect of GH on LFABP mRNA expression in vitro. The results emphasize the role of GH in the regulation of hepatic fatty acid metabolism.
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PMID:Hormonal regulation of liver fatty acid-binding protein in vivo and in vitro: effects of growth hormone and insulin. 960 75

The addition of oligofructose as a dietary fiber decreases the serum concentration and the hepatic release of VLDL-triglycerides in rats. Because glucose, insulin, insulin-like growth factor I (IGF-I) and gut peptides [i.e., glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)]) are factors involved in the metabolic response to nutrients, this paper analyzes their putative role in the hypolipidemic effect of oligofructose. Male Wistar rats were fed a nonpurified diet with or without 10% oligofructose for 30 d. Glucose, insulin, IGF-I and GIP concentrations were measured in the serum of rats after eating. GIP and GLP-1 contents were also assayed in small intestine and cecal extracts, respectively. A glucose tolerance test was performed in food-deprived rats. Serum insulin level was significantly lower in oligofructose-fed rats both after eating and in the glucose tolerance test, whereas glycemia was lower only in the postprandial state. IGF-I serum level did not differ between groups. GIP concentration was significantly higher in the serum of oligofructose-fed rats. The GLP-1 cecal pool was also significantly higher. In this study, we have shown that cecal proliferation induced by oligofructose leads to an increase in GLP-1 concentration. This latter incretin could be involved in the maintenance of glycemia despite a lower insulinemia in the glucose tolerance test in oligofructose-fed rats. We discuss also the role of hormonal changes in the antilipogenic effect of oligofructose.
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PMID:Insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide and insulin-like growth factor I as putative mediators of the hypolipidemic effect of oligofructose in rats. 964 91

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