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

Alterations of the insulin receptor and of glucose metabolism were examined in adipocytes from genetically diabetic KK mice. Compared with those from control C57BL/6 mice, adipocytes from KK mice showed weaker insulin binding and were less sensitive and less responsive to insulin with respect to 3-O-methylglucose uptake and [1-14C]glucose oxidation. However, insulin had no difference in effect between the two groups of mice with respect to [6-14C]glucose oxidation, glyceride-glycerol synthesis, or fatty acid synthesis from [1-14C]- and [6-14C]glucose. [1-14C]Glucose oxidation of KK cells was also insensitive to insulin mimics such as vitamin K5 and H2O2. When adipose tissues were precultured with insulin or insulin mimics for 24 h, adipocytes from C57BL/6 mice showed decreased insulin binding, but KK cells did not. When administered orally to KK mice for 2 weeks, ciglitazone made adipocytes more sensitive to insulin, more responsive to insulin with respect to glucose uptake and oxidation, and more capable of binding insulin. Impairment of the downregulation at the insulin receptor caused by exposure to insulin or insulin mimics was normalized by ciglitazone treatment in KK cells. In conclusion, KK cells are insulin-resistant due to defects of the insulin receptor and postbinding system in the glucose uptake and pentose pathways. In addition, regulation of the insulin receptor seems to be closely related to the postbinding system.
Diabetes Res Clin Pract 1988 Jul 13
PMID:Insulin receptor and postbinding defects in KK mouse adipocytes and improvement by ciglitazone. 341 9

The effect of short-term diabetes, 5 days after the administration of streptozotocin, on renal growth and the activity of alternative pathways of glucose metabolism was studied in immature (21-day-old) rats and in adult rats. The kidney weight increased by 28% in the adult diabetic rats, but by only 10% in the immature diabetic rats, relative to their age-matched control groups. The flux of glucose via the pentose phosphate pathway was increased 2-3-fold in the adult diabetic rats, but was unchanged in the immature diabetic group. Enzymes of this pathway (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase) increased by 29% and 77% respectively in adult diabetic rats; in the immature group they showed changes of +5% and +28% respectively. The rate of glucose phosphorylation increased significantly in both groups of diabetic rats; only minor changes were observed in oxidation via the tricarboxylic acid cycle. Increases of 40-50% were found in the activity of enzymes involved in UDP-glucose metabolism (phosphoglucomutase, UDPglucose pyrophosphorylase and UDPglucose dehydrogenase) and in lactate dehydrogenase in both young and adult animals. The results suggest a differential renal response to streptozotocin-diabetes according to the stage of renal growth and development, and it is proposed that the difference is related to the developmental emergence of aldose reductase. Enzymes involved in formation of ribose 5-phosphate and NADPH are strikingly increased in the adult diabetic, whereas metabolic functions dependent on a high ambient glucose concentration, e.g. synthesis of glycogen and glucuronate, are similarly affected in adult and immature diabetic groups, both showing certain aspects of 'glucose overutilization'.
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PMID:Renal hypertrophy in experimental diabetes. Effect of diabetes on the pathways of glucose metabolism: differential response in adult and immature rats. 371 86

It is shown in experiments on albino rats that dodeconium in therapeutic doses stimulates the glycolytic processes and inhibits the aerobic oxidation of glucose in the pentose phosphate cycle as well as the final stages of gluconeogenesis. Such an action of dodeconim leads to hypoglycemia and normalizes many indices of carbohydrate metabolism in alloxane diabetes.
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PMID:[Effect of dodeconium on carbohydrate metabolism]. 373 38

An examination was made of the effect of different periods of experimental diabetes on the activity of the pentose phosphate pathway in rat kidney. A rapid increase in kidney weight, expressed both in absolute terms and in terms of body weight, occurred shortly after the induction of diabetes. The activity of the enzymes of the oxidative segment of the pentose phosphate pathway and the flux of glucose through the pathway were both increased during the first 7 days after induction of diabetes. Thereafter, enzyme activity returned toward control levels, but the increased functional activity of the pathway, as measured using specifically labeled glucose, persisted. In contrast, transketolase was significantly depressed at the time of most rapid kidney growth. A positive correlation was found between the rate of kidney growth and the change in activity of glucose-6-phosphate dehydrogenase and a negative correlation with changes in transketolase activity. The possible roles of the oxidative and nonoxidative segments of the pentose phosphate pathway in the kidney in early diabetes-induced renal hypertrophy are discussed.
Diabetes 1985 May
PMID:Renal hypertrophy in experimental diabetes. Changes in pentose phosphate pathway activity. 398 75

1. The overall metabolic changes in lactating mammary gland in alloxan-diabetic and anti-insulin-serum-treated rats were assessed by measurement of the incorporation of (14)C from specifically labelled glucose, pyruvate and acetate into carbon dioxide and lipid, together with measurements of enzymes concerned with the pentose phosphate pathway and with citrate metabolism. 2. Alloxan-diabetes depressed the rate of formation of (14)CO(2) from [1-(14)C]glucose and [2-(14)C]glucose to approx. 10% of the control rate; this was partially reversed by addition of insulin in vitro. The quotient Oxidation of [1-(14)C]glucose/Oxidation of [6-(14)C]glucose fell from a value of 17.6 in the control group to 3.9 in the diabetic group and was restored to 14.3 in the presence of insulin in vitro. In keeping with these results it was shown that glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities were significantly decreased in alloxan-diabetic rats. 3. Alloxan-diabetes depressed the decarboxylation and the oxidation of labelled pyruvate, but not the oxidation of labelled acetate. 4. The synthesis of lipid from specifically labelled glucose was greatly decreased, that from [2-(14)C]pyruvate was almost unchanged and that from [1-(14)C]acetate alone was increased in alloxandiabetic rats. However, the stimulation of lipid synthesis from acetate by glucose was small in the alloxan-diabetic rats compared with the controls. Insulin in vitro partially reversed all these effects. Both citrate-cleavage enzyme and acetate thiokinase activities were decreased in alloxan-diabetic rats. 5. Treatment of rats with anti-insulin serum depressed the formation of (14)CO(2) from [1-(14)C]glucose and [2-(14)C]glucose, but increased that from [6-(14)C]glucose. This was completely restored by the presence of insulin in vitro. The quotient Oxidation of [1-(14)C]glucose/Oxidation of [6-(14)C]glucose fell from a value of 17.6 in the control group to 3.8 in the anti-insulin-serum-treated group. There were no changes in the activity of glucose 6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase, but the hexokinase distribution changed and the content of the soluble fraction increased significantly. 6. The synthesis of lipid from specifically labelled glucose was depressed in anti-insulin-serum-treated rats; this effect was completely reversed by addition of insulin in vitro to the tissue slices.
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PMID:Effect of alloxan-diabetes and treatment with anti-insulin serum on pathways of glucose metabolism in lactating rat mammary gland. 569 42

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. Measurements were made of the activities of the enzymes of the pentose phosphate pathway concerned in both the oxidative (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase) and the non-oxidative (ribose 5-phosphate isomerase, ribulose 5-phosphate epimerase, transketolase and transaldolase) reactions of this pathway, together with hexokinase and phosphoglucose isomerase, in adipose tissue in a variety of nutritional and hormonal conditions. 2. Starvation for 2 days caused a significant decrease in the activities of all the enzymes of the pentose phosphate pathway, with the exception of glucose 6-phosphate dehydrogenase, when expressed as activity/2 fat-pads; only the activities of ribose 5-phosphate isomerase and ribulose 5-phosphate epimerase were significantly decreased on the basis of activity/mg. of protein. Re-feeding with a high-carbohydrate or high-fat diet for 3 days restored the activity of all the enzymes of the pentose phosphate pathway to the range of the control values, with the exception of transketolase, which showed a marked ;overshoot' in rats re-fed with carbohydrate. Starvation for 3 days caused a marked decrease in the activities of glucose 6-phosphate dehydrogenase and transketolase. 3. On the basis of activity/two fat-pads, alloxan-diabetes caused a marked decrease, to about half the control value, in the activities of all the enzymes concerned in the pentose phosphate pathway, transketolase showing the smallest decrease; hexokinase and phosphoglucose isomerase activities were also decreased. Treatment with insulin for 3 and 7 days raised the activities to normal or supranormal values, transketolase showing the most marked ;overshoot' effect. On the basis of activity/mg. of protein the activity of none of the enzymes was significantly decreased in alloxan-diabetes; transketolase and transaldolase activities were raised above the control values. With insulin treatment for 3 or 7 days the activities of all the enzymes were significantly increased, except that of ribulose 5-phosphate epimerase at the shorter time-interval. Glucagon treatment did not alter any of the enzyme activities expressed on either basis. 4. Thyroidectomy caused a decrease of 30-40% in the activities of enzymes of the pentose phosphate pathway, except for transketolase activity, which fell to 50% of the control value. Little change occurred in adipose-tissue weight or protein content. 5. Adrenalectomy caused a decrease of 40% in the activity of glucose 6-phosphate dehydrogenase and of 20-30% in the activities of the remaining enzymes of the pentose phosphate pathway; hexokinase activity was also decreased. Treatment with cortisone for 3 days did not significantly raise the activity from that found in adrenalectomized rats. Treatment of normal rats with high doses of cortisone had no significant effect on the activities of the enzymes of the pentose phosphate pathway in adipose tissue. 6. The changes in enzyme activities are discussed in relation to: (a) the concept of constant-proportion groups of enzymes; (b) the known changes in the flux of glucose through alternative metabolic pathways; (c) the pattern of change found in liver with similar hormonal and dietary conditions.
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PMID:The pentose phosphate pathway of glucose metabolism. Hormonal and dietary control of the oxidative nd non-oxidative reactions and related enzymes of the cycle in adipose tissue. 581 81

The flux of glucose through the pentose phosphate pathway, important in relation to the provision of ribose 5-phosphate for nucleotide and RNA synthesis, was decreased by 70% in the diabetic rat heart in parallel with a similar decreased flux through the glycolytic route. A common factor linking the decreased flux through these alternative routes is the known fall in cardiac hexokinase; in these experiments there is a 50% decrease in Type II hexokinase (EC 2.7.1.1.) in both soluble and particulate fractions. The level of fructose 2,6-bisphosphate, a regulator of phosphofructokinase activity, is decreased by 20% in the alloxan diabetic rat heart, this may be a significant additional factor in the marked decrease in the flux of glucose through the glycolytic route in the myocardium in diabetes.
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PMID:Regulation of alternative pathways of glucose metabolism in rat heart in alloxan diabetes: changes in the pentose phosphate pathway. 636 95

The level of fructose 2,6-bisphosphate is markedly decreased in the rat V.renal gland in diabetes, falling to 23% of the control value. There is parallel decrease in the flux of 14C-labelled glucose through the glycolytic route and tricarboxylic acid cycle. Only minimal changes in hexokinase (EC 2.7.1.1.), a 22% decrease in Type I hexokinase of the soluble fraction, were observed, highlighting the probable significant involvement of fructose 2,6-bisphosphate in the regulation of glycolysis in the adrenal. In contrast, there was evidence for a marked rise in the flux of glucose through the pentose phosphate pathway, which may be linked to enhanced corticoid synthesis in the diabetic state.
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PMID:Regulation of glucose metabolism in rat adrenal gland in alloxan-diabetes: the possible role of fructose 2,6-bisphosphate. 654 41

Mellituria was studied in 83 subjects: 25 normal adults and children and 58 patients with several metabolic diseases. In comparison to the controls, no significant differences were found in 9 patients with cystinuria and in 2 patients with Apert's syndrome. The large excretion of glucose was the only important pattern of the 11 patients with insulin-dependent diabetes. In 23 patients with porphyria cutanea tarda a statistically significant increase in the excretion of pentose was observed. In 16 children with the classical form of phenylketonuria, a significant hypoexcretion of glucose was found. This latter observation could be explained by the carbohydrate metabolic alterations described in experimental hyperphenylalaninemia.
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PMID:Mellituria screening in some metabolic diseases. 685 89


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