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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies were made on whether glucose starvation causes fatty liver in pyridoxine-deficient male Wistar rats. Pyridoxine deficiency resulted in significantly lower levels of liver glucose than in pair-fed controls but no significant change in the serum glucose concentration. In non-starving animals, serum immuno-reactive insulin (IRI) was significantly lower in pyridoxine-deficient rats than in pair- or ad libitum-fed controls. Liver glucokinase activity in pyridoxine-deficient rats was also significantly lower than in ad libitum-fed controls. The extent of insulin deficiency was evaluated by examining the effect of administration of insulin on pyridoxine-deficient rats. Administration of insulin had no effect on the activity of liver glucokinase in pyridoxine-deficient rats, but induced the enzyme in ad libitum-fed controls. In response to a decrease in the activity of liver glucokinase or hexokinase in the deficient group, glycolytic activity, estimated as lactate production from glucose in the liver supernatant spun at 100,000 X g, was reduced to half the control level in pyridoxine-deficient rats. The effects of glucose administration on the liver lipid content, serum insulin and serum glucose were investigated. The serum glucose concentration was not significantly different in pyridoxine-deficient and control rats at any time after the glucose load. The level of serum IRI after the load was similar in the two groups after 30 min but then gradually decreased in the deficient group. The liver lipid content of the deficient rats tended to decrease whereas that of the controls remained unchanged throughout the experiment. Thus glucose starvation in pyridoxine-deficient rats is one factor responsible for fatty liver formation. Possible mechanisms of this phenomenon are discussed.
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PMID:Role of glucose on fatty liver formation in pyridoxine-deficient rats. 675 93

Regulation of synthesis and degradation of glucokinase, key enzyme of glucose metabolism in liver, was investigated in intact and adrenalectomized rats in vivo, using pulse-labeling experiments and a specific antibody against the enzyme. Refeeding glucose in starved rats resulted in a marked rise in glucokinase activity (from the starvation value 4.8 mU/mg protein to 9.6 mU/mg protein at 4 h, and to 21.8 mU/mg protein at 8 h), which closely correlated to the increase in enzyme synthesis by factor 1.7 at 4 h and 4.1 at 8 h. Similar alterations in enzyme activity and synthesis were observed after glucose refeeding in adrenalectomized/glucocorticoid-restored rats. In contrast, refeeding glucose in adrenalectomized rats led within 8 h only to a small elevation in enzyme activity (from the starvation value 4.2 mU/mg protein to 9.6 mU/mg protein) and a minor rise in enzyme synthesis (factor 1.7). Glucocorticoids per se were without effect on glucokinase activity and synthesis in starved rats. When adapted to pure glucose diet, intact, adrenalectomized and adrenalectomized/glucocorticoid-restored rats showed highly elevated levels in glucokinase (27, 23, 28 mU/mg protein, respectively). However, enzyme synthesis was elevated significantly only in intact and adrenalectomized/glucocorticoid-restored rats. Under these conditions glucokinase degradation was estimated by the double-pulse-labeling technique, applying [14C]leucine and [3H]leucine. From the 3H/14C ratios the apparent half-lives were calculated: 17 h in intact and adrenalectomized/glucocorticoid-restored rats, and 35 h in adrenalectomized rats. It is concluded that in vivo glucocorticoids not only exert a 'permissive' action on glucokinase induction, but also enhance the degradation of the enzyme.
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PMID:Hepatic glucokinase turnover in intact and adrenalectomized rats in vivo. 678 Mar 51

Glucokinase and hexokinase activities were measured in the periportal and perivenous zone of the liver acinus separated by microdissection. A microfluorimetric assay was established for the separate determination of both enzyme activities. Glucokinase activity was about 3.5-fold higher in the perivenous than in the periportal zone in fed male and female rats. after 24 h starvation this gradient was only slightly changed. Hexokinase showed an inverse gradient with about 1.5-fold higher activities in the periportal than in the perivenous zone in both fed and fasted animals. Since glucokinase is restricted to parenchymal cells and hexokinase is present predominantly or even exclusively in non-parenchymal cells, the heterogeneous distribution of glucokinase activity supports the model of a "metabolic zonation of liver parenchyma" with a predominance of glucose uptake in the perivenous and glucose release in the periportal hepatocytes.
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PMID:Reciprocal distribution of hexokinase and glucokinase in the periportal and perivenous zone of the rat liver acinus. 707 32

Rat liver glucokinase synthesis and degradation was estimated in fasted/fed and diabetic/diabetic-insulin-treated rats by the radioimmunological technique. Starvation and Streptozotocin-diabetes led to basal rates of synthesis and, consequently, to low levels in enzyme activity. In addition, a decrease in the apparent half-life from about 19 h in the fed or diabetic-insulin substituted to about 11 h in the starved or diabetic rat, respectively, was observed. Injection of Bt2cAMP into glucose-fed animals reduced glucokinase synthesis to basal levels within 90 min, without affecting enzyme activity. It is concluded that in metabolic states associated with elevated levels in tissue cAMP glucokinase synthesis is reduced to basal values and, in addition, its rate of degradation is significantly enhanced.
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PMID:Accelerated turnover of hepatic glucokinase in starved and streptozotocin-diabetic rat. 717 97

The role of different thyroid states on the rate of rat liver glucokinase synthesis and degradation was studied in vivo by the radioimmunochemical technique. In eu- and hyperthyroid starved rats, glucose refeeding induced a rapid and similar increase in glucokiase synthesis and activity, whereas in hypothyroid rats, only minor alterations in synthesis and activity was observed. 3,3',5'-Triiodo-L-thyronine substitution in hypothyroid animals restored the response of the enzyme within 24 h. The thyroid states per se had only a minor effect on glucokinase synthesis during the starvation period. In addition, in hypo-, eu-, and hyperthyroid rats adapted to a glucose diet, glucokinase degradation was estimated by double-pulse-labeling experiments, applying [14C]- and [3H]leucine. From the 3H/14C ratios, similar apparent half-lives were calculated: 17-19 h. It is concluded that thyroid hormones in their physiological range are an essential factor in the induction of hepatic glucokinase in vivo, exerting their action probably via a "permissive" effect, yet the degradation rate is unaffected by the thyroid state.
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PMID:Effect of different thyroid states on rat liver glucokinase synthesis and degradation in vivo. 728 95

The product of the c-myc proto-oncogene (c-Myc) is involved in the control of cell proliferation, differentiation, and apoptosis. It acts as a transcription factor that recognizes the CACGTG motif. This sequence has also been found in the glucose-responsive elements of genes involved in the control of liver glycolysis and lipogenesis. To determine whether c-Myc can regulate hepatic carbohydrate metabolism in vivo, transgenic mice that overexpress c-myc under control of the P-enolpyruvate carboxykinase (PEPCK) gene promoter have been generated. These mice showed a threefold increase in c-Myc protein in liver nuclei. Hepatocytes from transgenic mice were normal and did not acquire the fetal phenotype. However, transgenic mice showed higher levels (threefold) of L-type pyruvate kinase mRNA and enzyme activity than control mice. The increase in pyruvate kinase activity led to a three- to fivefold increase in liver lactate content and a fivefold induction of lactate production by hepatocytes in primary culture. The expression of the 6-phosphofructo-2-kinase gene was also increased in the liver of these transgenic mice. The induction of hepatic glycolysis was related with an increase in the expression (about fourfold) and activity (about threefold) of liver glucokinase, whereas no change was noted in hexokinase-I. This change in glucokinase activity led to an increase in both glucose 6-phosphate and glycogen contents in the liver of transgenic mice. The expression of the liver-specific glucose transporter GLUT2 was also increased in transgenic mice, whereas no change was noted in the mRNA concentration of GLUT1. Furthermore, the changes of liver glucose metabolism led to a marked reduction of blood glucose (25%) and insulin (40%) concentrations in starvation, whereas the fall in both was only 10% in fed mice. Thus, liver glucose metabolism could determine the blood glucose and insulin set points in the transgenic mice. All these results indicated that the increase in c-Myc protein was able to induce liver glucose utilization and accumulation, and suggested that c-Myc transcription factor is involved in the control in vivo of liver carbohydrate metabolism.
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PMID:Evidence from transgenic mice that myc regulates hepatic glycolysis. 764 6

The mutual role of glucose and insulin in the regulation of glucokinase and GLUT2 glucose transporter gene expression in pancreatic B-cells and liver has been studied in vivo in the rat. Glucokinase mRNA was quantified by competitive reverse-transcriptase PCR analysis, and GLUT2 mRNA by Northern-blot analysis in total RNA fractions. As in the liver, glucokinase mRNA decreased by 64% in pancreatic B-cells after starvation for 2 days and was induced 3-fold by short-term treatment (1 h) of the rats with oral glucose (4 g/kg body wt.). In contrast the sulphonylurea compound glibenclamide (0.1 mg/kg body wt.) did not significantly stimulate glucokinase gene expression in pancreatic B-cells. But glibenclamide caused a 4-fold increase of glucokinase mRNA in liver which was abolished by concomitant administration of diazoxide, a drug which antagonizes glibenclamide stimulated insulin secretion. GLUT2 gene expression was decreased by 50% in pancreatic B-cells and liver after starvation of the rats for 2 days. Neither short-term treatment (1 h) with glucose nor glibenclamide resulted in a significant increase of GLUT2 gene expression in pancreatic B-cells and liver. The results suggest that it is glucose which stimulates glucokinase gene expression in pancreatic B-cells whereas the transcriptional regulation of the glucokinase gene in liver is directed by insulin.
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PMID:Effects of glucose refeeding and glibenclamide treatment on glucokinase and GLUT2 gene expression in pancreatic B-cells and liver from rats. 775 56

The activity of liver glucokinase is controlled in the short term by the concentration of its substrate glucose and by a regulatory protein, which acts as a competitive inhibitor with respect to glucose. In mammalian species, the effect of this protein is modulated by fructose 6-phosphate, which reinforces the inhibition, and by fructose 1-phosphate which antagonizes it. In the rat, the regulatory protein is found in the two tissues that express glucokinase, i.e., the liver and the pancreatic islets. Of particular interest is the fact that the regulatory protein is absent from the liver in those species that have no hepatic glucokinase. These results indicate that the two proteins form a functional unit. The regulatory protein appears in rat liver before birth, whereas glucokinase is only synthesized after 15 days of extrauterine life. The concentration of regulatory protein in the liver of the adult rat decreases by about 50% during starvation and in diabetes mellitus. Under these conditions, the difference between the concentrations of regulatory protein and glucokinase remains constant at about 0.4-0.5 nmol/g.
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PMID:Short-term regulation of glucokinase. 782 39

The monomethyl ester of succinic acid (SME) was recently found to protect pancreatic islet B-cells against the impairment of glucose-stimulated insulin release caused by either glucopenia or starvation. The possible metabolic determinants of such a protective action are now scrutinized. After 180 min preincubation at 2.8 mM D-glucose in the presence of SME (10 mM), the oxidation of D-[U-14C]glucose, relative to either the utilization of D-[5-3H]glucose or the generation of 14C-labeled acidic metabolites, was higher than that after preincubation in the absence of SME and became close to that otherwise found after preincubation at 16.7 mM D-glucose. Likewise, after 3 days of culture at a low concentration of D-glucose (2.8 mM), the presence of SME in the culture medium tended to increase the subsequent oxidation of D-[6-14C]glucose and utilization of D-[5-3H]glucose. These two variables increased as a function of the concentration of D-glucose in the culture medium, this coinciding with a modest increase in hexokinase activity and a more pronounced increase in glucokinase activity. The presence of SME in the culture medium failed, however, to exert any obvious effect upon the respiration of the islets, suggesting that the protective action of the ester against glucopenia may also involve variables distinct from the metabolism of either endogenous or exogenous nutrients. Likewise, the fact that SME infusion to starved rats prevents the impairment of glucose-induced insulin release otherwise attributable to starvation may involve enzymatic determinants, such as a less severe decrease in glucokinase activity, metabolic variables, such as a greater relative increase in D-[U-14C]glucose oxidation relative to D-[5-3H]glucose utilization in response to a rise in extracellular D-glucose concentration, and other factors yet to be identified that participate in the secretory sequence at a site distal to those metabolic events triggered by D-glucose in the islet cells.
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PMID:Protective action of succinic acid monomethyl ester against the impairment of glucose-stimulated insulin release caused by glucopenia or starvation: metabolic determinants. 785 80

Type 2 diabetes is likely to be a polygenic disease, with a combination of major and minor genes affecting obesity, insulin secretion, and insulin action. Amongst these inputs, the 'thrifty genotype' hypothesis is most likely to apply to the predisposition to develop obesity, since the ability to store scarce fuels in periods of starvation could lead to obesity given a western lifestyle. Other genetic variations that were neutral with respect to food deprivation could be harmful with food excess. These could include 'defects' in islet cell function: examples could be mutations in the glucokinase gene and the genetic factors leading to amyloid deposition. The occurrence of associated lipid abnormalities or hypertension is probably due to additional specific genetic determinants that also become exaggerated by a modern lifestyle. The interactions between different genetic and environmental inputs are complex, and will probably be elucidated piecemeal as different genetic determinants are identified.
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PMID:Complex genetics of type 2 diabetes: thrifty genes and previously neutral polymorphisms. 821 Feb 95


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