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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Cataract formation in streptozotocin-induced diabetes in rats was reduced by approximately 85% when a diet rich in maize oil (300 g/kg diet) (fat diet) was given, thus confirming results of earlier studies. However, the concentration of sorbitol in the lens of diabetic animals remained high, the values for diabetic rats given the standard diet and the fat died being 65 and 40 mumol/g protein respectively. 2. With the standard diet, the fatty acid profile of the triglycerides of the epididymal fat pads was characterized by a greater relative proportion of saturated fatty acids for the diabetic animals compared to that for the normal animals. The fat diet moderated the tendency towards saturation in the diabetic animals. 3. The fat diet had other effects on the diabetic animals; these included a reduced mortality rate, increased body-weight, a decrease in the daily water intake, and in the daily urinary excretion of glucose and urea. 4. In the diabetic animals the fat diet had no effect on the specific activities in the liver of hexokinase (EC 2.7.1.1), glucokinase (EC 2.7.1.2), phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40). However, the specific activity of glucose-6-phosphatase (EC 3.1.3.9) was reduced, while that of malate dehydrogenase (decarboxylating) (NADP) (EC 1.1.1.40) was increased. The NAD+:NADH ratio, as calculated from liver pyruvate and lactate concentrations, tended to increase. 5. The results suggested that the fat diet moderated the long-term metabolic effects of diabetes.
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PMID:The effect of an unsaturated-fat diet on cataract formation in streptozotocin-induced diabetic rats. 13 11

Inbred strains of mice were surveyed for liver glucokinase activity. Mice of all strains studied could be distributed into three groups with high, intermediate, and low levels of enzyme activity. Genetic analysis using crosses and backcrosses with prototype high (C3H/HeJ) and low (RF/J) strains revealed that glucokinase activity was controlled by a single gene. The name "glucokinase" and gene symbol Gk are suggested for this gene. The Gka allele designates the strain with high glucokinase activity, while Gkb represents the allele in the strain with the low enzyme activity. The interaction of fasting and diabetes on the activity of glucokinase in these two strains is described.
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PMID:Genetic control of glucokinase activity in mice. 14 Dec 72

Intraperitoneal transplantation of collagenase-digested, isogeneic, neonatal rat pancreatic tissue successfully reversed streptozotocin-induced diabetes in 77% of recipients. The low serum immunoreactive insulin, hyperglycaemia, glycosuria and weight loss, characteristic of the diabetic animal, were corrected and the reduced activities of hepatic glucokinase and pyruvate kinase, and the low glycogen concentration of the liver of diabetic rats were restored to normal. Forty-three per cent of the successfully transplanted rats became normoglycaemic within 1 month of transplantation whereas 57% took from 1 to 6 months to achieve normoglycaemia and displayed a mild glucose intolerance when subjected to a glucose load. The rats which had not become normoglycaemic 6 months after transplantation showed some amelioration of the diabetic state, as shown by increased serum immunoreactive insulin and hepatic glycogen concentration and a slow weight gain compared with diabetic controls.
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PMID:Neonatal islet cell transplantation in the diabetic rat: effect on hepatic enzyme activity and glucose homeostasis. 14 94

Acitivites of the hepatic enzymes were determined in spontaneous diabetes rats. The activities of the enzymes were compared with those in normal rats and in streptozotocin diabetic rats. In the spontaneous diabetes rats, glycogen phosphorylase and glycogen synthase were 14.6 +/- 0.6 and 1.73 +/- 0.15 U respectively. The activities of both the enzymes were significantly increased. In the spontaneous diabetes rats glucokinase was 3.82 +/- 0.5 U showing a significant increase. On the contrary, the activity of the enzyme was decreased in the streptozotocin diabetic rats. Glucose-6-phosphatase was increased both in the spontaneous diabetes rats and in the streptozotocin diabetic rats. Fructose-1,6-diphosphatase was increased in the spontaneous diabetes rats. Glucose-6-phosphate dehydrogenase was increased in the spontaneous diabetes rats and decreased in the streptozotocin diabetic rats. In the spontaneous diabetes rats phosphofructokinase showed a reduction of the activity and glucose-6-phosphate dehydrogenase was elevated. These findings are consistent with the results of activities of the hepatic enzymes in adult-onset diabetic patients. These patterns of the hepatic enzymes in the spontaneous diabetes rats were different from those in the streptozotocin diabetic rats. From these patterns of activities of the hepatic enzymes, the spontaneous diabetes rats produced by repetition of selective breeding according to Goto et al. (1975,1976) are an excellent model of human adult-onset diabetes.
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PMID:Activities of hepatic enzymes in spontaneous diabetes rats produced by selective breeding of normal Wistar rats. 15 47

1. Glucokinase is one of four glucose phosphorylating enzymes present in rat liver. Its distinctive features are a high K-m for glucose (high-K-m isozyme) and a rather narrow substrate specificity. In contrast, the other three enzymes, collectively called hexokinases or low-K-m isozymes, exhibit low K-m values for glucose and a wider substrate specificity. 2. Glucokinase is present in the liver os mammals (with some exceptions), amphibians and lower reptiles; It is absent from higher reptiles and birds. The presence or absence of glucokinase may represent an evolutionary adaptation to feeding habits and other physiological peculiarities. Differences in the immunological behavior and in the kinetic parameters of glucokinases from different taxa suggest the operation of divergent evolution. 3. The levels of glucokinase in rat liver depend strictly on the supply of carbohydrate in the diet. Glycogen phosphorylase and glycogen synthetase behave similarly, whereas other carbohydrate-metabolizing enzymes depend on the provision of either protein or protein plus carbohydrate. Glucokinase decays with a half-life of 33 hr when rats are starved or fed a carbohydrate-free diet, and is induced by the administration of glucose. The adaptive character is not exhibited by all mammals, indicating evolutionary discrimination within the same class and even within the same single order Rodentia. Enzyme adaptation in the liver may partially explain the condition known as 'hunger diabetes'. 4. The endocrine system plays a paramount role in glucokinase adaptation, since insulin is essential for glucose-dependent glucokinase induction and, on the other hand, glucagon, catecholamines and cyclic AMP prevent the induction. Glucocorticoids and some pituitary hormones modulate the rate of induction. The mechanisms underlying the hormonal regulation of glucokinase levels are not well known. 5. The variations in liver glucokinase correspond to changes in the amount of enzyme protein as assessed by immunochemical titration. This fact agrees with the effects of inhibitors of protein synthesis on glucokinase induction. 6. An antiserum against rat glucokinase reacts with the enzyme from mammals and turtles but not with the amphibian enzyme. It does not react with low-K-m hexokinases from different sources. 7. The saturation function for glucose is sigmoidal in mammalian and amphibian glucokinases but not in glucokinase from lower reptiles. The Hill's coefficient is very constant with values about 1.6. The K0.5 (concentration for half saturation) values in the different species studied vary between 1.5 and 8 mM. These kinetic parameters may be considered as another adaptive feature aimed to give maximal efficiency to the liver uptake of glucose at the changeable concentrations in the blood resulting from variations in the amount of dietary glucose.
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PMID:Adaptive character of liver glucokinase. 16 20

The conversion of glucose into glucose 6-phosphate in an extract of isolated rat hepatocytes incubated in the presence of MgATP was studied spectrophotometrically at 340nm and also by a radiochemical procedure based on the release of (3)H from [2-(3)H]glucose. Both methods gave similar results. The glucose-saturation curve was sigmoidal and the shape of this curve was not influenced by the ionic composition of the incubation medium. The activity at 0.5mm-glucose was only 1-2% of V(max.), indicating a virtual absence of low-K(m) hexokinase in the preparation. The radiochemical method was also used for the determination of glucose phosphorylation by intact hepatocytes. The glucose-saturation curve was also markedly sigmoidal, but the s(0.5) (substrate concentration at half-maximal velocity) and the Hill coefficient were larger than in extracts of hepatocytes. These two parameters became smaller when cells were incubated in a medium in which Na(+) ions were replaced by K(+) ions. The increased rate of phosphorylation at low glucose concentration in a K(+) medium was accompanied by an increased rate of metabolite recycling between glucose and glucose 6-phosphate and also by an increased uptake of glucose. In both media phosphorylation of glucose was inhibited co-operatively by N-acetylglucosamine. Calculations indicate that this inhibition would reach 100% at saturation of the inhibitor, although at lower concentrations of N-acetylglucosamine it was smaller than expected from the known K(i) of N-acetylglucosamine for glucokinase. The rate of phosphorylation of glucose was proportional to the amount of glucokinase in hepatocytes from newborn rats and in conditions such as starvation and diabetes in which the total amount of glucokinase in the liver is decreased. In the same conditions, glucose 6-phosphatase activity was either normal or increased. It is concluded that the phosphorylation of glucose in isolated hepatocytes follows sigmoidal kinetics, which can be explained by the activity of glucokinase alone with no participation of low-K(m) hexokinase or of glucose 6-phosphatase.
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PMID:Phosphorylation of glucose in isolated rat hepatocytes. Sigmoidal kinetics explained by the activity of glucokinase alone. 21 56

Hyperinsulinemia was produced in fetal rhesus monkeys for 21 days in the last third of gestation by subcutaneous pork insulin injected at 19 U a day. Plasma insulin concentrations in treated fetuses (N = 4) were 3525 microU/ml. There was no difference in paired pre- and post-treatment fetal plasma glucose concentration. Activity of the hepatic enzymes that promote glucose utilization (glucokinase and hexokinase) and glycolysis (phosphofructokinase, pyruvate kinase, and pyruvate dehydrogenase) was unaffected. Similarly, glycogen metabolism enzymes (active and inactive synthase and phosphorylase) were unaltered. Two gluconeogenic enzymes (PEPCK and glucose-6-phosphatase) were diminished in the treated group compared with controls. Fetal hyperinsulinemia enhanced lipogenic and NADPH-producing enzyme activities, as evidenced by a twofold increase in fatty acid synthase and in citrate cleavage enzyme activity. Malic enzyme was absent. Hyperinsulinemia with euglycemia (1) increases the activity of enzymes that participate in lipogenesis, (2) decreases some of those controlling gluconeogenesis, and (3) has no effect on the enzymes of glycolysis.
Diabetes 1979 Dec
PMID:Chronic hyperinsulinemia in the fetal rhesus monkey: effects on hepatic enzymes active in lipogenesis and carbohydrate metabolism. 22 50

Streptozotocin treatment (125 mg/kg) in the Chinese hamster induced hyperglycaemia, hypoinsulinaemia, hyperglucagonaemia and changes in body, liver, pancreas, stomach, kidney and adipose tissue weights. The pancreatic reserves of insulin and glucagon in the diabetic animals were low, but stomach glucagon high. These animals showed high levels of phosphoenolpyruvate carboxykinase and low levels of glucokinase, hexokinase, isocitrate dehydrogenase and malic enzyme, but normal levels of pyruvate kinase in the liver. Increases in lactate dehydrogenase subunit B and isozymes 2, 3 and 4 were also observed in the liver, but not in the epididymal fat pad, of the diabetic animals. N-Acetyl-beta-D-glucosaminidase was elevated in plasma, liver and heart, but not in the kidney of the treated animals. Renal alpha-galactosidase and beta-glucosidase were depressed, whereas beta-galactosidase and alpha-glucosidase remained essentially normal. These features indicated that there were considerable differences between the biochemical disorders associated with streptozotocin-diabetes in the Chinese hamster and the published observations in the rat.
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PMID:Streptozotocin-induced diabetes in the Chinese hamster. Biochemical and endocrine disorders. 59 Jun 51

Streptozotocin-induced diabetes suppressed the normal development of the nine glycolytic and lipogenic enzyme activities measured. With the exception of NADP-isocitrate dehydrogenase, insulin replacement therapy induced increased activities of the enzymes in streptozotocin-treated rats. Insulin appeared to have a specific effect on the activities of glucokinase, ATP-citrate lyase, malic enzyme, and glucose-6-P-dehydrogenase.
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PMID:Effect of streptozotocin diabetes and insulin administration on some liver enzyme activities in the post-weaning rat. 72 37

We describe a codon 299 mutation in the glucokinase gene in a British pedigree with maturity-onset diabetes of the young (MODY) resulting in a substitution of glycine to arginine. One out of fifty patients diagnosed with classical late-onset type 2 diabetes mellitus was also found to have this mutation. All nine relatives of this patient who have inherited the mutation have type 2 diabetes, although six others without the mutation are also present with diabetes. The discovery that glucokinase mutations can cause MODY and was also found in ten affected members of a pedigree with type 2 diabetes in which MODY had not previously been considered indicates that diagnosis based on molecular pathology will be helpful in understanding the aetiology of type 2 diabetes.
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PMID:Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes. 130 65


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