Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Glucokinase was absent from chicken liver and only the low Km hexokinases, inhibited by AMP, ADP but not ATP, were present. 2. The Km of chicken liver glucose-6-phosphatase for glucose-6-phosphate was reduced from 5.65 to 3.75 mM following starvation, and the enzyme was inhibited by glucose. 3. Starvation of chickens for 24 hr slightly lowered the hexokinase activity and doubled glucose-6-phosphatase activity; it did not change subcellular distribution of the enzymes. Oral glucose rapidly restored the activities to fed values. 4. It was concluded that glucose uptake into, and efflux from, chicken hepatocytes, was regulated by the activity and kinetic characteristics of glucose-6-phosphatase and by the glucose-6-phosphate concentration, and that the hexokinases had little regulatory function.
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PMID:Glucose phosphorylation and dephosphorylation in chicken liver. 23 87

Glucokinase (EC 2.7.1.2) is the signal-recognition enzyme in pancreatic B-cells for initiation of glucose-induced insulin secretion. We show here that both the glucokinase and glucose-transporter GLUT-2 genes are regulated physiologically. Fasting decreased B-cell glucokinase and glucose-transporter GLUT-2 mRNA in pancreatic B-cells as well as in liver, whereas refeeding induced expression of both genes. In pancreatic B-cells a approximately 4.4 kb glucokinase-related mRNA was detectable, in addition to the 2.8 kb form. This approximately 4.4 kb glucokinase transcript was drastically decreased during refeeding. The 2.8 kb mRNA, which is typical for pancreatic B-cells, was accompanied after refeeding by a 2.4 kb mRNA species typical for liver glucokinase. Starvation primarily decreased the 2.8 kb pancreatic B-cell glucokinase mRNA species. The concordant regulation of both genes may represent the basis for the physiological regulation of glucose-induced insulin secretion at a transcriptional level.
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PMID:Regulation of glucokinase and GLUT-2 glucose-transporter gene expression in pancreatic B-cells. 195 86

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. 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

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

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

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

Glucokinase (GK, hexokinase type IV) is required for the accumulation of glycogen in adult liver and hepatoma cells. Paradoxically, mammalian embryonic livers store glycogen successfully in the absence of GK. Here we address how mammalian embryonic livers, but not adult livers or hepatoma cells, manage to accumulate glycogen in the absence of this enzyme. Hexokinase type I or II (HKI, HKII) substitutes for GK in hepatomas and in embryonic livers. We engineered FTO2B cells, a hepatoma cell line in which GK is not expressed, to unveil the modifications required to allow them to accumulate glycogen. In the light of these results, we then examined glycogen metabolism in embryonic liver. Glycogen accumulation in FTO2B cells can be triggered through elevated expression of HKI or either of the protein phosphatase 1 regulatory subunits, namely PTG or G L. Between these two strategies to activate glycogen deposition in the absence of GK, embryonic livers choose to express massive levels of HKI and HKII. We conclude that although the GK/liver glycogen synthase tandem is ideally suited to store glycogen in liver when blood glucose is high, the substitution of HKI for GK in embryonic livers allows the HKI/liver glycogen synthase tandem to make glycogen independently of the glucose concentration in blood, although it requires huge levels of HK. Moreover, the physiological consequence of the HK isoform switch is that the embryonic liver safeguards its glycogen deposits, required as the main source of energy at birth, from maternal starvation.
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PMID:Hepatic glycogen synthesis in the absence of glucokinase: the case of embryonic liver. 1816 36