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

The activities of hepatic enzymes involved in glucose phosphorylation and NADPH production were studied in male and female obese Zucker rats (fa/fa) and lean control animals (Fa/-). The fa/fa animals were heavier and had higher serum insulin levels than the lean rats. The glucokinase activity and the total glucose phosphorylation capacity were also higher in the obese animals. The activity of glucokinase correlated significantly with serum insulin levels. The glucose-6-phosphate phosphohydrolase activity was unchanged or slightly lowered in the obese rats. The activity of malic enzyme was elevated in the obese animals.
Diabetes Res 1989 Mar
PMID:Activity of hepatic glucose phosphorylating and NADPH generating enzymes in Zucker rats. 268 Feb 27

The effect of oral administration of vanadate on the transport and hydrolytic components of the glucose-6-phosphatase system in liver homogenates from streptozotocin-induced diabetic rats was examined. Blood glucose was normalized in diabetic rats receiving 0.8 mg/ml vanadate but a catabolic effect was observed on body and liver weight. Significant changes in the coupled reactions for glucose-6-phosphate transport by T1 and hydrolysis by the enzyme were noted. The dramatic elevation in the maximal velocity of glucose-6-phosphatase brought about by diabetes was suppressed by vanadate administration. As a result, the relationship between T1 and the enzyme returned to the normal range. It is concluded that the suppression of glucose-6-phosphate hydrolysis in diabetes may contribute to the normalizing effect of vanadate on blood glucose.
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PMID:Suppression of the hepatic glucose-6-phosphatase system in diabetic rats by vanadate. 285 61

Energy stores and intermediates of carbohydrate metabolism were investigated in the freeze-clamped cerebral cortex of the fetus and fasted neonate born to a diabetic canine mother. Prior studies in these same pups demonstrated circulating hyperinsulinemia, depressed free fatty acid levels, and attenuated gluconeogenesis. Hepatic and muscle tissue also demonstrated augmented levels of glycogen, triglycerides, and amino acids. In the present investigation, cerebral tissue from these same pups of diabetic mothers also demonstrated enhanced fetal cerebral glucose and glycogen content. After 24 h of neonatal fasting, cerebral glycogen content declined to values lower than in control pups. Cerebral cortical levels of glucose-6-phosphate, fructose-6-phosphate, lactate, citrate, alpha-ketoglutarate, and malate were not altered, while oxaloacetate was higher at 3 and 9 h and fructose-1,6-diphosphate was higher at 9 and 24 h in the IDM pups. Adenine nucleotide levels and the energy charge were equivalent to those in control pups at each time interval. In contrast, cerebral cortical amino acids of the glutamate group were enhanced in the fetus or neonate of the diabetic mother. Cerebral cortical alanine was increased from 3 to 24 h while aspartate and glutamate were augmented in the fetus and fasted IDM newborn pup. Glutamine was increased at 6 and 24 h, while gamma-aminobutyrate was elevated in the fetus. Cerebral ammonia concentration was not altered. The augmented stores of cerebral carbohydrate and amino acid pools in the fetus and neonate after maternal canine diabetes may serve as oxidizable substrates for the brain during periods of attenuated systemic fuel availability.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Feb
PMID:Enhanced cerebral substrate pools in the fetus and neonate of the diabetic canine mother. 285 42

Dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one; DHEA) and its conjugates are abundant circulating steroids that originate largely from the adrenal cortex. Their levels decline profoundly with age in human beings of both sexes, as the incidence of most cancers rises. Low levels of these steroids have been associated with the presence and risk of development of cancer. Administration of DHEA to rodents produces protection against spontaneous tumors and chemical carcinogenesis, suppresses weight gain without significantly affecting food intake, ameliorates the severity of diabetes in genetically diabetic mice, and restrains autoimmune processes. DHEA and related steroids also depress the mitogenic effects of carcinogens, tumor promoters and plant lectins, and block viral and carcinogen-induced cell transformations. DHEA and certain congeners are also potent and quite specific inhibitors of mammalian glucose-6-phosphate dehydrogenases. We have observed that the conversion of 3T3-L1 and 3T3-F442A preadipocyte clones to the adipocyte phenotype, in response to appropriate differentiation stimuli (fetal calf serum, insulin, dexamethasone, and 1-methyl-3-isobutylxanthine), is blocked by DHEA and other steroidal inhibitors of glucose-6-phosphate dehydrogenase. The structural requirements for blocking adipocyte differentiation and for inhibiting glucose-6-phosphate dehydrogenase are closely correlated. Evidence is reviewed suggesting that the inhibition of glucose-6-phosphate dehydrogenase is central to the anticarcinogenic and differentiation-blocking actions of DHEA and related steroids. The 3T3 preadipocyte clones provide a valuable system for the analysis of the mechanisms of the effects of DHEA on growth, differentiation and carcinogenesis.
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PMID:Modulation of growth, differentiation and carcinogenesis by dehydroepiandrosterone. 296 Jan 33

The kinetics of hydrolysis of ATP were determined for the renal Na,K-ATPase, in the K+ conformation, modified with glucose-6-phosphate. There was a shift in the ATP hydrolysis kinetics from negative kinetic co-operativity for the control enzyme preparations to substrate inhibition kinetics for the modified enzyme preparations. The effect was reversible and stabilized after NaBH4 reduction. Approximately 4 moles of glucose-6-phosphate were incorporated per mole of Na,K-ATPase (based on MW of 150,000 daltons). Similar substrate inhibition kinetics were observed for the renal Na,K-ATPase isolated from several human subjects with mature onset diabetes.
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PMID:Glucose-6-phosphate modification of bovine renal Na,K-ATPase: a model for changes occurring in the human renal medulla in diabetes. 299 41

In diabetic animals and humans, stimulation of liver glycogen synthesis has been reported after administration of a large parenteral fructose load. The effects of an oral fructose load have not been examined previously. In the diabetic state, glycogen synthase phosphatase activity is reduced, and synthase D (the inactive form) is a poor substrate for the phosphatase. Thus, activation of synthase to the synthase R and synthase I (R + I) (active) forms by fructose would not be expected. We have determined that oral fructose administration does stimulate glycogen synthesis and have examined the mechanism by which this is accomplished. In 24-h-fasted alloxan diabetic rats, basal liver glycogen was higher than in normal rats (8.3 +/- 1.8 vs. 3.0 +/- 0.5 mg/g wet wt). After fructose (4 g/kg) was given, the initial rate of glycogen synthesis was normal in diabetic rats, but total glycogen synthesis was reduced. By 240 min, liver glycogen increased to 18 +/- 4.0 mg/g wet wt in diabetic rats versus 30.5 +/- 1.5 mg/g wet wt in normal rats. Synthase R + I was low and did not increase significantly (0.063 +/- 0.006 to 0.064 +/- 0.010 U/g wet wt) after fructose administration to the diabetic animals. Phosphorylase a did not decrease significantly during the period of active glycogen synthesis. In the diabetic rats, glucose-6-phosphate increased by 84% (0.103 +/- 0.010 to 0.184 +/- 0.020 mumol/g wet wt) within 10 min and remained elevated above the control level. UDPglucose decreased from 0.336 +/- 0.013 to 0.271 +/- 0.011 mumol/g wet wt at 10 min and remained below the control level.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1986 Jun
PMID:Mechanism of stimulation of liver glycogen synthesis by fructose in alloxan diabetic rats. 308 65

The influence of a non-ketonic, chronically diabetic state (60 mg/kg streptozotocin) on cardiac function and metabolism was studied under in vivo conditions by inserting a Millar-tip catheter into the left ventricle and in the model of the isolated perfused heart. In vivo heart rate and maximal left ventricular systolic pressure were reduced after a diabetes duration of 4 and 12 weeks. The maximal rise and fall in left ventricular pressure progressively declined with the duration of diabetes. The reduced myocardial function was associated with a loss in ATP and adenine nucleotides. In the perfused heart of chronically diabetic rats, heart function was also impaired and could not be restored in vitro by perfusion with glucose and insulin. In the presence of octanoate--a substrate which can be metabolized independently from insulin--heart function of diabetic rats was improved, but remained lowered as compared to controls. Since the content of myocardial creatine phosphate was reduced in diabetic hearts perfused with octanoate, these findings indicate that the suppression of cardiac performance is not only a result of an impaired glucose metabolism, but of a more general defect in energy provision and utilization. In contrast to hearts of acutely diabetic, ketotic rats most often used, the rate of lipolysis of endogenous triglycerides and the contribution of fatty acids to energy production was low in the chronically diabetic state. Inhibition of fatty acid oxidation by an inhibitor of carnitine palmitoyltransferase (CPTI) did not restore the reduced responsiveness of diabetic hearts to insulin. Analysis of intracardiac metabolites revealed that in the perfused heart of chronically diabetic rats glucose-6-phosphate and citrate do not accumulate as in hearts of ketotic, diabetic rats. Therefore, the impaired glucose metabolism presumably reflects a reduced uptake of glucose rather than in inhibition of glycolysis as in hearts of ketotic, diabetic rats.
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PMID:Myocardial performance and metabolism in non-ketotic, diabetic rat hearts: myocardial function and metabolism in vivo and in the isolated perfused heart under the influence of insulin and octanoate. 354 78

We studied the effect of spontaneous long-term (9-10 months) diabetes on the heart of Chinese hamsters (CHAD strain) to elucidate the relationship between diabetes mellitus and cardiomyopathy. The diabetic hamsters, aged approximately 11 months, showed body weight loss, hyperglycemia (mean fasting plasma glucose 402 mg/dl), hypoinsulinemia, hyperlipidemia and ketonemia. The diabetic hamsters showed reduced activities of cytoplasmic glycolytic key enzymes; hexokinase, pyruvate kinase and phosphofructokinase, increases in cardiac glycogen and glucose-6-phosphate contents and a 40% decrease in cardiac ATP content, indicating decreased energy production. An accumulation of myocardial triglyceride and cholesterol was found in the diabetic hamsters. In addition, the cardiac norepinephrine content was increased in the diabetic hamsters, suggesting the presence of autonomic nervous disorder. Increased heart weight and thickening of the septum and both ventricular walls were found in the diabetic hamsters. Light-microscopic analysis revealed that 42.9% of the diabetic hamsters had myocardial degeneration without any vascular lesion of extramural large and intramural small vessels, whereas the non-diabetic controls had no myocardial or vascular lesions. These data suggest that the diabetic Chinese hamsters had cardiomyopathy, which is possibly caused by extravascular factors such as metabolic or autonomic nervous disorder although conclusive evidence is lacking.
Diabetes Res Clin Pract
PMID:Metabolic and morphological changes of the heart in Chinese hamsters (CHAD strain) with spontaneous long-term diabetes. 366 31

Peripheral hyperinsulinaemia usually found in conventionally treated Type 1 (insulin-dependent) diabetic patients may have deleterious metabolic effects. We have used a hyperinsulinaemic model to examine intermediary metabolism in two key peripheral tissues, aorta and muscle. Nine pigs were immunized with crystalline insulin. Subsequently, they showed an insulin-binding capacity of 86.2 +/- 25.0 pmol/l and fasting total serum insulin of 3.9 +/- 3.1 nmol/l (control range 0.034-0.072 nmol/l), impaired glucose tolerance after oral glucose tolerance testing, significantly elevated levels of peripheral venous serum free insulin and C-peptide, and increased mean post-prandial free insulin/glucose ratios. The immunized pigs showed marked elevation of aorta and muscle triglycerides compared with control pigs (n = 15) but similar levels of non-esterified fatty acids. The glucose-6-phosphate-dehydrogenase, malic enzyme and 3-hydroxyacyl-CoA-dehydrogenase activities were all increased significantly (by 50%-300%) in both aorta and muscle. Phosphofructokinase was decreased in both tissues. Hexokinase was increased in muscle alone whereas pyruvate kinase was significantly decreased in aorta. Glyceraldehyde-3-phosphate dehydrogenase activity was not significantly different in aorta and muscle. Thus in insulin immunized pigs with normal beta-cell function and pronounced peripheral hyperinsulinaemia there was increased peripheral lipogenic activity. These findings have potentially important implications with regard to macrovascular disease in diabetes.
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PMID:Aorta and muscle metabolism in pigs with peripheral hyperinsulinaemia. 388 16

It has recently been shown that insulin sensitivity of skeletal muscle glucose uptake and glycogen synthesis is increased after a single exercise session. The present study was designed to determine whether insulin is necessary during exercise for development of these changes found after exercise. Diabetic rats and controls ran on a treadmill and their isolated hindquarters were subsequently perfused at insulin concentrations of 0, 100, and 20,000 microU/ml. Exercise increased insulin sensitivity of glucose uptake and glycogen synthesis equally in diabetic and control rats, but insulin responsiveness of glucose uptake was noted only in controls. Analysis of intracellular glucose-6-phosphate, glucose, glycogen synthesis, and glucose transport suggested that the exercise effect on responsiveness might be due to enhancement of glucose disposal. After electrical stimulation of diabetic hindquarters in the presence of insulin antiserum, insulin sensitivity of 3-O-methylglucose transport was increased to the same extent as in muscle from healthy rats stimulated in the presence of insulin at 50 microU/ml. Furthermore, in muscle depleted of glycogen by contractions, transport of 3-O-methylglucose was increased in the presence of insulin antiserum and in the absence of increased regional perfusate flow. It is concluded that after exercise, increased sensitivity of muscle glucose metabolism to insulin can be found in the absence of insulin during exercise, but still involves increased membrane transport of glucose. At maximal insulin concentrations, the enhancing effect of exercise on glucose uptake may involve enhancement of glucose disposal, an effect that is probably less in muscle from diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Oct
PMID:Increased muscle glucose uptake after exercise. No need for insulin during exercise. 389 6


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