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)

1. The physiological factors that prevent the precocious appearance of glucokinase activity in the 13-day-old rat that can be induced by oral glucose administration were explored. 2. Evidence is presented that the galactose component of milk sugar is inhibitory. In the absence of this inhibitory galactose, the amount of glucose necessary to effect appreciable induction is greater than that present in milk. 3. The induction is prevented both by administration of mannoheptulose, which inhibits insulin release, and by excess insulin; the amount of insulin available therefore seems to be critical. 4. The inhibition of induction by galactose does not appear to be via competition with glucose but by enhancing insulin release and thereby making this excessive. The relative amounts of glucose and insulin appear to be important in regulating glucokinase induction. 5. The precocious induction of glucokinase by glucose is inhibited by simultaneous treatment with approriate amounts of adrenaline, glucagon, dibutyryl cyclic AMP or isoprenaline but not by vasopressin or angiotensin II. 6. No single cause of glucokinase induction in neonatal rat liver can be recognized. The process is subject to regulation by many factors at a time subsequent to when competence to synthesize the enzyme has been established.
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PMID:Factors that prevent the premature appearance of glucokinase in neonatal rat liver. 699 15

A generalized characteristic of all aging populations is the progressively impaired ability to adapt to an altered environment. The increased latent period for the response of hepatic glucokinase activity to glucose in aging rats is one specific example of this phenomenon. The disturbed regulation of hepatic glucokinase activity probably is the consequence of altered control of the secretion of key hormones rather than effects of aging on hepatic function. Such changes in the regulation of hormone secretion already are documented or suspected at least for insulin, glucagon, adrenal glucocorticoids, and thyroid hormones. The regulation of insulin secretion by glucose is altered during aging within the predominant population of islets of Langerhans, perhaps by differences in cell-to-cell communication within these islets. Once the nature of limiting biochemical modifications is established within a specific cell population, it may be possible to identify the origin of at least a distinct set of gerontological phenomena.
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PMID:The role of hormones in changing adaptive mechanisms during aging. 700 18

The role of glucocorticosteroid and thyroid hormone and of glucagon and insulin in the pre- and postnatal developmental formation of carbamoyl-phosphate synthase, ornithine transcarbamoylase, arginase, glutamate dehydrogenase, tyrosine aminotransferase, glucose-6-phosphatase, hexokinase and glucokinase activities in rat liver was investigated. Glucocorticosteroids and a low insulin/glucagon ratio always stimulate formation of carbamoyl-phosphate synthase, ornithine transcarbamoylase, arginase, glutamate dehydrogenase, tyrosine aminotransferase and glucose-6-phosphatase, while glucocorticosteroids and a high insulin/glucagon ratio stimulate formation of glucokinase. Thyroid hormone stimulates the formation of carbamoyl-phosphate synthase, arginase and tyrosine aminotransferase only before birth, whereas it stimulates the formation of glutamate dehydrogenase and glucose-6-phosphatase both before and after birth. Ornithine transcarbamoylase activity is depressed after thyroid-hormone treatment before and after birth. DNA content is always decreased by glucocorticosteroids and increased by thyroid hormone. The effect of these hormones on hexokinase is complex, probably due to different responses of the constitutive isozymes. With the exception of the effects of thyroid hormone on carbamoyl-phosphate synthase, arginase and tyrosine aminotransferase before birth, which may be indirect, the responses of enzyme activities and DNA content to treatment with glucocorticosteroid hormones, glucagon, insulin and thyroid hormone are qualitatively the same in fetuses, neonates, sucklings, weanlings and adults. Thus, the developmental profiles of the enzyme clusters reflect the changing levels of the relevant hormones. The enzymes that are stimulated by glucocorticosteroids and the insulin/glucagon ratio show increases in enzyme activity perinatally and around weaning, and relatively low activities in between, while those enzymes that are additionally stimulated by thyroid hormone differ in exhibiting relatively high activities between birth and weaning.
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PMID:Multihormonal control of enzyme clusters in rat liver ontogenesis. II. Role of glucocorticosteroid and thyroid hormone and of glucagon and insulin. 702 60

Glucose uptake/production was studied as a function of varied glucose loads in isolated perfused livers from glucagon-treated alloxan-diabetic rats. Uptake of D-[U-14C]glucose was seen at all levels studied - 9.5-71 mM. In studies with unlabelled D-glucose carried out in the absence of 3-mercaptopicolinate, livers of diabetic rats showed a net production of glucose with perfusate glucose levels less than 22 mM. Above this level, these livers exhibited a time- and concentration-dependent net uptake of glucose for a period of 20-30 min. When 4 mM 3-mercaptopicolinate, which inhibited gluconeogenesis from endogenous substrates, was included in perfusates, a continuous net uptake of unlabelled glucose was observed at all levels above 4 mM. This lowering of the null-point, cross-over glucose concentration was shown to relate mechanistically to the observed reduction in steady-state hepatic glucose 6-phosphate level produced by mercaptopicolinate. The need for supplemental mechanisms of glucose utilization by high Km hepatic enzyme(s) operative in the virtual absence of insulin-dependent glucokinase also is indicated by these observations and by kinetic analysis.
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PMID:Stimulation by 3-mercaptopicolinate of net glucose uptake by perfused livers from diabetic rats. 715 Jun 40

The influence of recombinant human interleukin-6, the major mediator of the inflammatory response in liver, on the glucagon- and insulin-dependent induction of the phosphoenolpyruvate carboxykinase and glucokinase gene, respectively, was monitored on the level of gene transcription, mRNA abundance and enzyme activity in cultured rat hepatocytes. As control markers of the interleukin-6-induced acute-phase response the mRNA levels of the acute phase proteins alpha 2-macroglobulin and beta-fibrinogen were determined. In cultured rat hepatocytes, recombinant human interleukin-6, added simultaneously with glucagon and insulin, lowered the maximal increase in glucagon-induced phosphoenolpyruvate carboxykinase mRNA levels after 2 hr and the maximal increase in glucokinase mRNA levels after 3 hr to about 30%, respectively. It inhibited the glucagon-induced increase in phosphoenolpyruvate carboxykinase gene transcription and phosphoenolpyruvate carboxykinase enzyme activity, as well as the insulin-induced increases in glucokinase gene transcription and glucokinase enzyme activity. Recombinant human interleukin-6 increased the mRNA levels of the acute-phase proteins alpha 2-macroglobulin and beta-fibrinogen gradually over 4 to 6 hr. Recombinant human interleukin-6, added 2 hr after glucagon or 3 hr after insulin at the maximum of the hormone-induced enzyme mRNA levels, almost doubled the decay rate of phosphoenolpyruvate carboxykinase mRNA and glucokinase mRNA. The results show that interleukin-6 induced the expression of inflammatory proteins and simultaneously inhibited the hormone-induced expression of enzymes of intermediary metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition by recombinant human interleukin-6 of the glucagon-dependent induction of phosphoenolpyruvate carboxykinase and of the insulin-dependent induction of glucokinase gene expression in cultured rat hepatocytes: regulation of gene transcription and messenger RNA degradation. 752 6

Differential developmental regulation of pancreas-specific genes has not been reported for the human fetal pancreas. We have therefore undertaken a systematic, quantitative analysis of the transcriptional levels of various genes in the human pancreas at different stages of fetal and postnatal development. Using sensitive ribonuclease protection assays, in situ hybridization, and the polymerase chain reaction, our results indicate the following: 1) Transcriptional levels of insulin and amylin remain lower in the fetal than in the adult pancreas, whereas glucagon and somatostatin mRNA levels are consistently greater after 14 wk gestation than postnatally. These results are in agreement with previous immunohistochemical studies of these gene products. 2) The reg gene exhibits a 20-fold increase in mRNA levels after 16 wk gestation. The gene is expressed exclusively in the acinar cells and does not colocalize with insulin. This restricted exocrine expression does not indicate a direct role for the reg gene in islet development. 3) Glucose transporter 2 and glucokinase mRNA are detectable as early as 13 wk gestation and remain low throughout development. Glucose transporter 1 reaches adult transcriptional levels by 18 wk gestation. The early detection of glucose transporter 2 and glucokinase implies that lack of expression of these "glucose sensor" genes does not account for the known insensitivity of the fetal beta-cells to glucose.
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PMID:Developmental gene expression in the human fetal pancreas. 752 96

It has been previously demonstrated that the enteric hormone glucagon-like peptide-1 (7-36 amide) (GLP-1) has acute effects on glucose-induced insulin secretion by RIN 1046-38 cells. In this study, we investigated the effects of extended exposure of RIN 1046-38 cells to GLP-1 and examine the mechanism by which GLP-1 synergizes with glucose in stimulating insulin secretion. Compared with cells cultured with glucose alone, incubation of cells with glucose plus 1 or 10 nM GLP-1 for 12 or 24 h significantly increased insulin release by about 3-fold, intracellular insulin content by 1.5-fold, and insulin messenger RNA (mRNA) by almost 2.5-fold. The insulinotropic effects of GLP-1 on RIN 1046-38 cells were accompanied by an up-regulation of both glucose transporter-1 (GLUT-1) and hexokinase I mRNA by about 2-fold. mRNA levels of GLUT-2 and glucokinase, which were low in controls, were unchanged by GLP-1 treatment. Treatment of cells with a transcription inhibitor, actinomycin D, demonstrated that elevated insulin mRNA levels after a GLP-1 exposure are mainly due to stabilization of the mRNA. In contrast, the elevated mRNA levels of GLUT-1 and hexokinase I are the result of increased transcription stimulated by GLP-1 exposure. Actinomycin D blunted the GLP-1 effect on insulin release but did not affect GLP-1 mediated elevation of insulin mRNA. This suggests that actinomycin D inhibits the transcription of the proteins necessary for insulin biosynthesis and insulin release, such as GLUT-1 and hexokinase I. Our study suggests that the mechanisms by which extended exposure of RIN 1046-38 cells to GLP-1 increases glucose-stimulated insulin secretion include significant up-regulation of glucose-sensing elements.
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PMID:Glucagon-like peptide-1 affects gene transcription and messenger ribonucleic acid stability of components of the insulin secretory system in RIN 1046-38 cells. 758 24

Hormonal and non-hormonal regulation of glucokinase gene expression was investigsted in cultured rat islet cells. To measure glucokinase mRNA in pancreatic islet cells, the competitive PCR method was adopted. With this method, GKmRNA levels can be measured using only 0.1-1.0 microgram of total RNA isolated from cultured rat islet cells. Following 24 h preculture with 5.5 mM glucose, islet cells were cultured for 24 or 8 h with hormonal or non-hormonal factors. Glucokinase mRNA levels tended to increase, but not significantly, at 16.7 mM glucose compared to those at 5.5 mM glucose. Treatment with either 1 microM T3 or 1 microM glucagon resulted in a decrease in the glucokinase mRNA level with 16.7 mM glucose, whereas 1 microM insulin had no effect on glucokinase mRNA. Five mM dibutyryl cyclic AMP decreased the glucokinase mRNA level with 16.7 mM glucose, but cycloheximide did not block this inhibitory effect, suggesting that the effect of glucagon may be mediated by cyclic AMP and that protein synthesis is not involved in the response. Furthermore, the islet glucokinase mRNA level increased in response to 1 microM glibenclamide with 5.5 mM glucose and the response was abolished by cycloheximide, which indicates the involvement of protein synthesis in the glibenclamide-induced mRNA change. An 8-bromo-cyclic GMP (1 microM) and vanadate (1 microM) did not affect the islet GKmRNA level. These findings suggested that thyroid hormone and glucagon-cyclic AMP suppress, and glibenclamide increases the GKmRNA level in cultured rat islet cells, and that insulin, cyclic GMP and vanadate differentially affect glucokinase gene expression in pancreatic islet cells and in the liver.
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PMID:Regulation of glucokinase gene expression in cultured rat islet cells: the inhibitory effects of T3 and glucagon, and the stimulatory effect of glibenclamide. 766 33

Glucokinase and phosphoenolpyruvate carboxykinase are key enzymes of glucose metabolism in the rat liver. The former is considered to be instrumental in regulating glucose hepatic release/uptake according to the glycaemia level, and cytosolic phosphoenolpyruvate carboxykinase is a major flux-generating enzyme for gluconeogenesis. The level of expression of both enzymes and the regulation of their mRNAs in the human liver cell were investigated. Surgical biopsies of liver from patients undergoing partial hepatectomies and parenchymal hepatocytes derived from the biopsies were used to assay glucokinase, hexokinase and phosphoenolpyruvate carboxykinase activities. Hepatocytes were placed in culture and the actions of insulin, glucagon and cAMP on glucokinase and phosphoenolpyruvate carboxykinase mRNAs were studied. The main results are: (a) glucokinase accounts for 95% of the glucose phosphorylation activity of human hepatocytes, although this fact is masked in assays of total liver tissue; (b) glucokinase activity is set at a lower level in human hepatocytes than in rat hepatocytes, and vice-versa for the gluconeogenic enzyme phosphoenolpyruvate carboxykinase; and (c) as previously shown in rat liver, glucokinase and phosphoenolpyruvate carboxykinase mRNAs are regulated in a reciprocal fashion in human hepatocytes, insulin inducing the first enzyme and repressing the latter, whereas glucagon has opposite effects. These data have interesting implications with respect to metabolic regulation and intracellular hormone signaling in the human liver.
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PMID:Glucokinase and cytosolic phosphoenolpyruvate carboxykinase (GTP) in the human liver. Regulation of gene expression in cultured hepatocytes. 773 62

Glucosamine, a potent inhibitor of glucokinase (hexokinase IV or D), was used to estimate the contribution of this enzyme to glucose phosphorylation in freshly isolated rat hepatocytes and its sensitivity to fructose 6-phosphate in situ. Experiments with radiolabelled glucosamine indicated that this amino sugar, at concentrations of 5 or 40 mM, readily penetrated hepatocytes to reach in 1 min a total (i.e., glucosamine+metabolites) intracellular concentration equal to 0.8-1.2-fold its extracellular concentration. In marked contrast, N-acetylglucosamine barely penetrated the cells. The detritiation of [2-3H]glucose, used to estimate glucose phosphorylation in intact cells, was inhibited by glucosamine much more potently than by N-acetylglucosamine, half-maximal effects being reached at about 2.5 and 30 mM respectively. Extrapolation of the data indicated that about 12% of the detritiation was resistant to glucosamine. Dihydroxyacetone (10 mM), lactate (10 mM) + pyruvate (1 mM), and glucagon (1 microM) increased up to 8-fold the concentration of hexose 6-phosphates (glucose 6-phosphate+fructose 6-phosphate) and, against expectations, modestly decreased the detritiation rate measured in the absence of glucosamine. In the presence of 40 mM glucosamine, these agents increased the detritiation rate, which then positively correlated with the concentration of hexose 6-phosphates. This hexose 6-phosphates-dependent detritiation was sensitive to inhibition by vanadate, and was also catalysed by gel-filtered cell-free extracts, as well as by liver microsomes in the presence of phosphoglucoisomerase; it can be explained by an exchange reaction catalysed by glucose-6-phosphatase. When this exchange reaction is taken into account, it appears that the rate of glucose detritiation attributable to glucokinase decreases when the concentration of hexose 6-phosphates increases. This is in agreement with the known effect of fructose 6-phosphate to potentiate the inhibition of glucokinase by its regulatory protein.
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PMID:Glucosamine-sensitive and -insensitive detritiation of [2-3H]glucose in isolated rat hepatocytes: a study of the contributions of glucokinase and glucose-6-phosphatase. 775 69

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