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

Experimentally-induced alloxan diabetes was characterized in rats by a marked increase in the blood glucose level and by a number of disturbances in the concentration of metabolites and the activity of the enzymes of carbohydrate metabolism in the liver. Stimulation of gluconeogenesis in diabetes was judged by reduction of the redox condition of free NAD- and NADP-couples, by the increase in the concentration of phosphoenolpyruvate, malic oxaloacetate and phosphoenolpyruvate carboxykinase activity of the liver. Nicotinamide in a dose of 50 mg per 100 g of body weight caused a marked reduction in the blood glucose level of diabetic rats. An increase of the [NAD+]/[NADN], [NADP+]/[NADPN] ratio, a reduction of the concentration of phosphoenolpyruvate, malate and phosphoenolpyruvate carboxylase activity pointed to the inhibition of gluconeogenesis and stimulation of glycolysis in the liver of diabetic rats given nicotinamide.
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PMID:[Hypoglycemic effect of nicotinamide in rats with alloxan diabetes]. 2 43

1. Approx. 85% of liver phosphoenolpyruvate carboxykinase is associated with the mitochondrial fraction in the fed guinea pig. Enzyme activity is unchanged in diabetes, but doubles during starvation. In contrast with earlier reports, both cytoplasmic and mitochondrial activities were found to be increased. 2. In kidney cortex, total enzyme activity is increased in both starved and diabetic animals. These changes are associated with increases in the cytoplasmic activity alone. 3. In diabetic animals the mean blood-glucose concentration was 23.1 mM. Other blood metabolites were lower than those in the rat, and the animals did not show significant ketosis. 4. Changes in the rates of gluconeogenesis from lactate and propionate paralleled those in phosphoenolpyruvate carboxykinase activity.
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PMID:The effects of starvation and experimental diabetes on phosphoenol-pyruvate carboxykinase in the guinea pig. 14 29

1. The development of glycerolkinase before and after birth was investigated in liver and kidney of rat and hamster. In rat liver, enzyme activity increased very slowly before birth and rapidly thereafter, reaching adult values at the 6th day of postnatal life. In hamster liver, glycerolkinase was considerably elevated already in utero, increased dramatically within the 1st day of postnatal life and reached adult values at the end of the 1st week. The development of hepatic glycerolkinase was compared with that of hepatic phosphoenolpyruvate carboxykinase of rat and hamster up to the 20th day of postnatal life. The different time-courses of the levels of these two enzymes before and after birth as well as the known kinetics of serum insulin, glucagon and corticosterone during that time suggested that none of these hormones is involved in the perinatal development of hepatic glycerolkinase activity. In contrast to liver, kidney glycerolkinase activity in both, rat and hamster, showed a delayed increase during the first week of postnatal life followed by a more pronounced elevation to adult values within the following 2 weeks. 2. When liver and kidney glycerolkinase activity was investigated during starvation (+/- refeeding), in alloxan diabetes(+/- insulin) and after adrenalectomy (+/- cortisol) no significant change in enzyme activity per g tissue could be detected either in liver or in kidney. However, total hepatic glycerolkinase activity was diminished during starvation as a consequence of decreasing liver weight. 3. Incorporation of U-[14C]-glycerol into CO2, lipids and glucose + glycogen by rat liver and kidney cortex slices was studied under the above gluconeogenetic conditions. Despite unchanged glycerolkinase activity in both organs, gluconeogenesis from glycerol was enhanced during starvation and in chronic alloxan diabetes, and could be reversed by refeeding and insulin replacement, respectively. 4. Feeding 20% of linolic acid to normal, alloxan-diabetic or adrenalectomized rats resulted in a significant increase in glycerolkinase activity in liver but not in kidney. 5. From the present findings it is suggested that the first step of gluconeogenesis from glycerol in liver and kidney is not influenced by glucagon, insulin and glucocorticoids, which are generally believed to regulate the rate of gluconeogenesis from non-glycerol precursors, but probably by the change in blood glycerol concentration.
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PMID:Glycerolkinase--a regulatory enzyme of gluconeogenesis? 18 91

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

The activity of several regulatory enzymes representing the pathways of glycolysis, gluconeogenesis, NADPH generation and lipogenesis was measured in rat placenta maternal and foetal livers on the 20th day of gestation. Streptozotocin diabetes, induced on the 12th day of gestation, or 48 h of fasting did not induce adaptive changes in the activity of placental enzymes while producing a typical insulin deficiency pattern in maternal liver. Foetal liver enzyme activities were unaffected by fasting and in diabetes showed changes suggestive of foetal hyperinsulinaemia. A small increase was observed in the activity of placental pyruvate kinase and a small decrease in that of PEP carboxylase in diabetic and in glucocorticoid-treated rats; these changes were reciprocal to those in the maternal liver and were attributed to hyperglycaemia, as was the increase in placental glycogen. Lack of response to insulin deficiency and to other endocrine alterations indicates that placenta is not sensitive to stimuli which induce adaptive alterations in hepatic enzymes. The only consistent change found in placental enzyme activities was a decrease associated with gestational age.
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PMID:Placental enzymes of glycolysis, gluconeogenesis and lipogenesis in the diabetic rat and in starvation. Comparison with maternal and foetal liver. 72 Jul 82

1. Neither alloxan-diabetes nor starvation affected the rate of glucose production in hepatocytes incubated with lactate, pyruvate, propionate or fructose as substrates. In contrast, glucose synthesis with either alanine or glutamine was increased nearly 3- and 12-fold respectively, in comparison with that in fed rabbits. 2. The addition of amino-oxyacetate resulted in about a 50% decrease in glucose formation from lactate in hepatocytes isolated from fed, alloxan-diabetic and starved rats, suggesting that both mitochondrial and cytosolic forms of rabbit phosphoenolpyruvate carboxykinase function actively during gluconeogenesis. 3. Alloxan-diabetes resulted in about 2-3-fold stimulation of urea production from either amino acid studied or NH4Cl as NH3 donor, whereas starvation caused a significant increase in the rate of ureogenesis only in the presence of alanine as the source of NH3. 4. As concluded from changes in the [3-hydroxybutyrate]/[acetoacetate] ratio, in hepatocytes from diabetic animals the mitochondrial redox state was shifted toward oxidation in comparison with that observed in liver cells isolated from fed rabbits.
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PMID:Effect of alloxan-diabetes on gluconeogenesis and ureogenesis in isolated rabbit liver cells. 74 58

Previous investigations of the phosphoenolpyruvate carboxykinase (PEPCK) gene have been conducted using rats. In a recent comparative study, we investigated, for the first time, the effects of fasting, refeeding, alloxan-induced diabetes, and insulin treatment on the levels of PEPCK mRNA in mouse liver, kidney, and adipose tissues. As in rats, fasting and diabetes induced, while insulin repressed, hepatic PEPCK mRNA. In contrast, the response of renal PEPCK mRNA to fasting, refeeding, and diabetes in mice differed quantitatively with that in rats: fasting caused a twofold increase in mice and a fourfold increase in rats. Moreover, diabetes, which induces renal PEPCK mRNA indirectly by causing acidosis in rats, was without effect in mice. In adipose tissue, the results of previous studies in both rats and mice have shown that the amount of PEPCK protein and its rate of synthesis are increased by fasting and diabetes and decreased by refeeding and insulin treatment. Thus, it was surprising to find that fasting, refeeding, alloxan-induced diabetes, and insulin treatment had no effect on adipose tissue PEPCK mRNA in either rats or mice.
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PMID:Regulation of phosphoenolpyruvate carboxykinase mRNA in mouse liver, kidney, and fat tissues by fasting, diabetes, and insulin. 146 Aug 46

We have studied the presence of the messenger RNA (mRNA) for the cytosolic enzyme, phosphoenolpyruvate carboxykinase (PEPCK), in rat lung by Northern blot hybridization to a complementary DNA (cDNA) probe. Lung from normal rats contained substantial amounts of this mRNA, although its relative concentration was approximately six times lower than in liver. Fasting produced an eightfold increase in the content of the enzyme mRNA in lung, which could be reverted to normal values by glucose refeeding. Induced diabetes also resulted in a sevenfold increase of the levels of PEPCK mRNA in lung. Dexamethasone, thyroid hormone, dibutyryl cyclic adenosine monophosphate (cAMP), histamine, and serotonin also induced important accumulations of the enzyme mRNA without affecting the concentration of beta-tubulin mRNA measured as reference. Thus, the PEPCK gene appears to be regulated in a similar manner in lung and liver. The results suggest that PEPCK may be involved in lung metabolism in starvation, diabetes, and other specific hormonal situations.
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PMID:Detection and hormonal regulation of the mRNA for cytosolic phosphoenolpyruvate carboxykinase in rat lung. 162

Hepatic glucose production is stimulated in vitro twice as effectively by pulsatile as by continuous glucagon, given equivalent time-averaged doses. Efficacy studies of pulsatile insulin have yielded conflicting results. In the rat hepatoma cell line H-4-II-E-C3, insulin rapidly (t1/2 15 min) inhibits transcription of the gene and lowers mRNA levels for the gluconeogenic enzyme. PEPCK via a receptor-mediated process. We attached H-4-II-E-C3 cells to Cytodex-3 microcarriers and used a perifusion column system to test whether pulsatile insulin is more or less effective than equivalent time-averaged doses of continuous insulin. PEPCK transcription was induced by inclusion of cAMP analogue 8-(4-chlorophenyl-thio)-cAMP (0.1 mM) and dexamethasone (0.5 microM) in the perifusion medium. Three columns were exposed either to continuous, pulsatile, or no insulin. After 3 h, total nucleic acid was extracted, and mRNA(PEPCK) was measured with a sensitive-solution hybridization assay. Continuous insulin inhibited PEPCK expression in a dose-dependent fashion with EC50 1 x 10(-11) M. Equivalent time-averaged amounts of insulin delivered as pulses achieved significant inhibition but less effectively than continuous insulin. The apparent EC50 for pulsatile insulin increased from 2 x 10(-11) M to 5 x 10(-11) M as the oscillatory period was raised from 5 to 20 min, respectively. These observations suggest that insulin-mediated inhibition of PEPCK gene transcription is diminished by a pulsatile mode of administration in marked contrast to the pulse enhancement demonstrated for glucagon-mediated hepatic glucose production.
Diabetes 1991 Aug
PMID:Insulin pulses less effective than continuous insulin in inhibiting PEPCK mRNA levels stimulated by cAMP and dexamethasone in perifused hepatoma cells. 165 Mar 13


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