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

The present study investigates the effect of thyroid and glucocorticoid hormones on the induction of hepatic glucokinase mRNA activity, enzyme synthesis and activity in starved/refed adrenalectomized, thyroidectomized and intact rats. In intact rats glucose refeeding resulted within 2 h in a more than tenfold increase in the functional messenger, followed by a corresponding increase in glucokinase synthesis and, a little later, in enzyme activity. Glucokinase mRNA and synthesis remained elevated at this level for about further 6 h. Then the mRNA activity and enzyme synthesis declined considerably to a new steady state (a factor of about 4 above the starvation level) within a further 8 h, while enzyme activity remained constantly elevated. The half-life of glucokinase mRNA, as determined after administration of cordycepin, was identical during the different refeeding periods. Thus the overshoot phenomenon, provoked by carbohydrate refeeding, in glucokinase mRNA is not explained by alteration of the glucokinase mRNA decay rates. In thyroidectomized or adrenalectomized rats, glucose refeeding resulted in only a small increase in glucokinase mRNA, synthesis and activity. Application of thyroid hormones in thyroidectomized rats, refed a carbohydrate-rich diet, enhanced the specific mRNA considerably within 8-10 h, while it took 20-24 h to enhance glucokinase mRNA by glucocorticoids in adrenalectomized rats refed a carbohydrate-rich diet. The decay in translatable glucokinase mRNA, as determined after administration of cordycepin, was identical in the hypothyroid and euthyroid fed state, while adrenalectomy resulted in a significant decrease in the specific mRNA half-life. We conclude that refeeding a carbohydrate-rich diet rapidly stimulates glucokinase mRNA regeneration showing overshoot kinetics. 3,3',5-Triiodothyronine in its physiological concentration significantly enhances the response in glucokinase mRNA at the nuclear level, while glucocorticoids in their physiological concentration predominantly stabilize the translatable glucokinase mRNA.
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PMID:Regulation of hepatic glucokinase gene expression. Role of carbohydrates, and glucocorticoid and thyroid hormones. 383 Jan 79

1. Rates of insulin secretion, glucose utilization, lactate output, incorporation of glucose into glycogen, contents of glucose 6-phosphate, fructose 1,6-diphosphate and ATP, and maximally extractable enzyme activities of hexokinase, high-K(m) glucose-phosphorylating activity (;glucokinase'), glucose 6-phosphatase and unspecific acid phosphatase were measured in isolated pancreatic islets from fed and 48-h-starved mice. 2. In the fed state insulin secretion from isolated islets was increased five- to six-fold when the extracellular glucose concentration was raised from 2.5mm to 16.7mm; 5mm-caffeine potentiated this effect. The secretory response to glucose of islets from mice starved for 48h was diminished at all glucose concentrations from 2.5mm up to approx. 40mm. Very high glucose concentrations (60mm and above) restored the secretory response to that found in the fed state, suggesting that the K(m) value for the overall secretory process had been increased (approx. fourfold) by starvation. Addition of 5mm-caffeine to islets from starved mice also restored the insulin secretory response to 2.5-16.7mm-glucose to normal values. 3. Extractable hexokinase, ;glucokinase', glucose 6-phosphatase and unspecific phosphatase activities were not changed by starvation. 4. Glucose utilization and glycolysis (measured as the rate of formation of (3)H(2)O from [5-(3)H]glucose over a 2h period) was decreased in islets from starved mice at all glucose concentrations up to approx. 55mm. At still higher glucose concentrations up to approx. 100mm, there was no difference between the fed and starved state, suggesting that the K(m) value for the rate-limiting glucose phosphorylation had been increased (approx. twofold) by starvation. Preparation of islets omitting substrates (glucose, pyruvate, fumarate and glutamate) from the medium during collagenase treatment lowered the glucose utilization measured subsequently at 16.7mm-glucose by 38 and 30% in islets from fed and starved mice respectively. Also the 2h lactate output by the islets at 16.7mm extracellular glucose was diminished by starvation. Incorporation of glucose into glycogen was extremely low, but the rate of incorporation was more than doubled by starvation. 5. After incubation for 30min at 16.7mm-glucose the content of glucose 6-phosphate was unchanged by starvation, that of ATP was increased and the concentration of (fructose 1,6-diphosphate plus triose phosphates) was decreased. 6. Possible mechanisms behind the correlated impairment in insulin secretion and islet glucose metabolism during starvation are discussed.
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PMID:The effect of starvation on insulin secretion and glucose metabolism in mouse pancreatic islets. 415 24

1. In the isolated perfused liver from 48h-starved rats, glycogen synthesis was followed by sequential sampling of the two major lobes. 2. The fastest observed rates of glycogen deposition (0.68-0.82mumol of glucose/min per g fresh liver) were obtained in the left lateral lobe, when glucose in the medium was 25-30mm and when gluconeogenic substrates were present (pyruvate, glycerol and serine: each initially 5mm). In this situation there was no net disappearance of glucose from the perfusion medium, although (14)C from [U-(14)C]glucose was incorporated into glycogen. There was no requirement for added hormones. 3. In the absence of gluconeogenic precursors, glycogen synthesis from glucose (30mm) was 0-0.4mumol/min per g. 4. When livers were perfused with gluconeogenic precursors alone, no glycogen was deposited. The total amount of glucose formed was similar to the amount converted into glycogen when 30mm-glucose was also present. 5. The time-course, maximal rates and glucose dependence of hepatic glycogen deposition in the perfused liver resembled those found in vivo in 48h-starved rats, during infusion of glucose. 6. In the perfused liver, added insulin or sodium oleate did not significantly affect glycogen synthesis in optimum conditions. In suboptimum conditions (i.e. glucose less than 25mm, or with gluconeogenic precursors absent) insulin caused a moderate acceleration of glycogen deposition. 7. These results suggest that on re-feeding after starvation in the rat, hepatic glycogen deposition could be initially the result of continued gluconeogenesis, even after the ingestion of glucose. This conclusion is discussed, particularly in connexion with the role of hepatic glucokinase, and the involvement of the liver in the glucose intolerance of starvation.
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PMID:Glycogen synthesis in the perfused liver of the starved rat. 465 86

Liver homogenates of avian species, but not of mammals, form glycogen from glucose, mannose, fructose and galactose. Incorporation of labelled glucose, fructose and mannose, but not of labelled galactose, into glycogen is diluted isotopically by unlabelled glucose. Except for fructose, glycogen formation from other substrates by pigeon liver homogenates compares favourably with that from the same substrates in pigeon liver slices. Optimum conditions for glycogen synthesis from glucose by pigeon liver homogenate are: medium of incubation, 0.175m-sucrose-45mm-potassium chloride-15mm-glycylglycine buffer, pH7.5; concentration of substrate, 15mm; concentration of tissue, less than 120mg./ml.; temperature of incubation, 37-43 degrees ; atmosphere, oxygen. Uncouplers of oxidative phosphorylation, Ca(2+), EDTA, PP(i), 2-deoxyglucose 6-phosphate and microsomal fraction of rat liver are inhibitory to glycogen synthesis from glucose. Starvation of pigeons for 24 and 48hr. leads to a slight stimulation of glycogen synthesis in their liver homogenates as compared with fed controls. Pigeon liver homogenates can be separated into subcellular fractions that on reconstitution can synthesize glycogen. All the enzymes of the glycogen pathway except soluble high-K(m) glucokinase are present in pigeon liver.
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PMID:Studies on glycogen synthesis in pigeon liver homogenates. Incorporation of hexose into glycogen. 558 93

1. Measurements were made of the non-oxidative reactions of the pentose phosphate cycle in liver (transketolase, transaldolase, ribulose 5-phosphate epimerase and ribose 5-phosphate isomerase activities) in a variety of hormonal and nutritional conditions. In addition, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities were measured for comparison with the oxidative reactions of the cycle; hexokinase, glucokinase and phosphoglucose isomerase activities were also included. Starvation for 2 days caused significant lowering of activity of all the enzymes of the pentose phosphate cycle based on activity in the whole liver. Re-feeding with a high-carbohydrate diet restored all the enzyme activities to the range of the control values with the exception of that of glucose 6-phosphate dehydrogenase, which showed the well-known ;overshoot' effect. Re-feeding with a high-fat diet also restored the activities of all the enzymes of the pentose phosphate cycle and of hexokinase; glucokinase activity alone remained unchanged. Expressed as units/g. of liver or units/mg. of protein hexokinase, glucose 6-phosphate dehydrogenase, transketolase and pentose phosphate isomerase activities were unchanged by starvation; both 6-phosphogluconate dehydrogenase and ribulose 5-phosphate epimerase activities decreased faster than the liver weight or protein content. 2. Alloxan-diabetes resulted in a decrease of approx. 30-40% in the activities of 6-phosphogluconate dehydrogenase, ribose 5-phosphate isomerase, ribulose 5-phosphate epimerase and transketolase; in contrast with this glucose 6-phosphate dehydrogenase, transaldolase and phosphoglucose isomerase activities were unchanged. Treatment of alloxan-diabetic rats with protamine-zinc-insulin for 3 days caused a very marked increase to above normal levels of activity in all the enzymes of the pentose phosphate pathway except ribulose 5-phosphate epimerase, which was restored to the control value. Hexokinase activity was also raised by this treatment. After 7 days treatment of alloxan-diabetic rats with protamine-zinc-insulin the enzyme activities returned towards the control values. 3. In adrenalectomized rats the two most important changes were the rise in hexokinase activity and the fall in transketolase activity; in addition, ribulose 5-phosphate epimerase activity was also decreased. These effects were reversed by cortisone treatment. In addition, in cortisone-treated adrenalectomized rats glucokinase activity was significantly lower than the control value. 4. In thyroidectomized rats both ribose 5-phosphate isomerase and transketolase activities were decreased; in contrast with this transaldolase activity did not change significantly. Hypophysectomy caused a 50% fall in transketolase activity that was partially reversed by treatment with thyroxine and almost fully reversed by treatment with growth hormone for 8 days. 5. The results are discussed in relation to the hormonal control of the non-oxidative reactions of the pentose phosphate cycle, the marked changes in transketolase activity being particularly outstanding.
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PMID:The pentose phosphate pathway of glucose metabolism. Hormonal and dietary control of the oxidative and non-oxidative reactions of the cycle in liver. 579 34

1. Glucokinase and hexokinase activities have been determined in the livers of newborn rats and attempts made to influence in vivo the development of the glucokinase. 2. Glucokinase first appears in rat liver about 16 days after birth and adult activities are reached 10-12 days later. Evidence is presented which indicates that this represents synthesis of new protein. Hexokinase activities remain constant throughout the period of glucokinase development. 3. Both exogenous glucose and insulin are necessary for the natural development of glucokinase, for this is retarded in starved and alloxan-diabetic neonatal rats. 4. The absence of glucokinase during the first 2 weeks of extrauterine life in the rat is not due to lack of insulin. 5. Attempts to advance the time at which glucokinase first appears by infusions of glucose, insulin and chlorpropamide alone and in various combinations have resulted in marginal effects only. 6. When rats are starved for 3 days during the period of glucokinase development and then re-fed, glucokinase is more rapidly synthesized, indicating that the potential ability to synthesize glucokinase continues to develop throughout the period of starvation. 7. Some possible reasons for the comparatively late development of glucokinase are discussed.
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PMID:The development of hepatic glucokinase in the neonatal rat. 588 29

Rats preferring ethanol were distinct from water-consuming animals in a decreased level of immunoreactive insulin im blood serum as well as in glucokinase activity of liver tissue. Per oral loading with glucose, 4 g/kg of body mass, enabled to detect a difference in the sugar phosphorylation via hexokinase and glucokinase reactions as well as the dissimilar sensitivity of the insulin system to glucose in the ethanol-, water-consuming and intermediate animals. Ethanol-consuming rats were more resistant to the effect of starvation during 48 hrs. The data obtained suggest that the characteristic properties of glucose metabolism in ethanol-consuming rats appear to be responsible for increased consumption of ethanol, which is used as optimal energy source, metabolized via pathways which did not involve the glycolytic pathway.
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PMID:[Characteristics of glucose metabolism in rats with different preferences for alcohol]. 609 27

Activities of key enzymes in hepatic glucose utilization were compared between obese (C57BL/6J ob/ob) mice, their lean controls and outbred Swiss albino mice in the fed condition and during fasting. As liver hyperplasia and hepatocyte hypertrophy were present in the ob/ob mice at 4-5 months of age and changes in hepatic cellularity did occur with fasting, enzyme activity was expressed on the basis of protein, DNA, and wet weight. In the fed state, activities of glucokinase + hexokinase (glucose phosphorylating capability), phosphofructokinase and pyruvate kinase were significantly greater in livers of ob/ob mice when compared to those of the lean control. Glucokinase + hexokinase activities in livers of ob/ob mice remained significantly higher throughout the 48 h fast yet the activities of hepatic phosphofructokinase and pyruvate kinase, when expressed per g wet wt or mg protein, decreased so that a statistical difference from the fasted lean control was no longer detected. When expressed per 100 g body weight, hepatic glucokinase + hexokinase as well as phosphofructokinase and pyruvate kinase activities in obese mice were higher both in the fed and fasted states when compared to lean controls in the comparable nutritional condition. This increased capacity of key enzyme activities in hepatic glucose utilization can be attributed to liver hyperplasia found in ob/ob mice in both the fed and fasted condition. While higher hepatic glucose phosphorylating capability was maintained during fasting, the elevated specific activities of hepatic phosphofructokinase and pyruvate kinase in the obese mouse in the fed state decreased with starvation to values found in the lean control.
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PMID:Enzyme activities of hepatic glucose utilization in the fed and fasting genetically obese mouse at 4-5 months of age. 624 16

The mRNA activity coding for rat liver glucokinase was measured in vivo under different hormonal and nutritional conditions. Starvation resulted in minimal levels of glucokinase mRNA activity. Glucose refeeding caused a 4-fold induction of glucokinase mRNA within 48 h, which followed similar alterations in enzyme activity. Minimal values for glucokinase mRNA were also measured in diabetic animals fed glucose and were significantly elevated by insulin injection within 1.5 h. Administration of dibutyryl cyclic AMP to glucose-fed rats caused a rapid loss of the specific mRNA. The half-life of glucokinase mRNA, determined after the administration of cordycepin to glucose-fed animals, was approximately 40 min. This half-life was unaffected by the administration of dibutyryl cyclic AMP. Glucokinase mRNA was reduced 60% in glucose-fed adrenalectomized or thyroidectomized rats. The activity of the glucokinase mRNA agreed well with the measured rates of enzyme synthesis. These data indicate that insulin regulates hepatic glucokinase synthesis in vivo by increasing glucokinase mRNA; its effect is reduced by the absence of glucocorticoids or thyroid hormones and is rapidly antagonized by cyclic AMP.
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PMID:Rapid action of insulin and cyclic AMP in the regulation of functional messenger RNA coding for glucokinase in rat liver. 632 5

Starvation refeeding experiments were conducted in rats to test the hypothesis that adaptation of glucokinase (the high Km component of glucose phosphorylation) could be the major determinant of glucose metabolism of pancreatic islet cells and of glucose-stimulated insulin release. It was found that glucokinase of islet homogenates, glucose use by intact isolated islets, and glucose-induced insulin release as studied in a perifusion system were decreased after 24 h of fasting, whereas P-fructokinase and 3-P-glyceraldehyde DH were unaltered. After extended fasting (e.g., 120 h) all three enzymes were decreased but glucose use did not change any further. Refeeding normalized all parameters. These and previous results support the concept that glucokinase serves as the adaptive beta-cell glucoreceptor relating blood glucose to insulin release.
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PMID:Adaptation of glycolytic enzymes: glucose use and insulin release in rat pancreatic islets during fasting and refeeding. 645 66


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