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

In alloxan-induced diabetes the content of riboflavin and FMN goes up in all of the subcellular fractions and that of FAD in the nuclear liver fraction alone. While administration of insulin to control animals reduces the riboflavin and FMN level in all of the subcellular fractions of the liver, in the diabetic animals such a decline is observed in the nuclei alone. Insulin brings down the FAD level in the nuclear liver fraction of both the control and test animals. An additional introduction of riboflavin depresses and that of FMN - raises the FAD content in diabetic animals as compared to controls.
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PMID:[Metabolism of riboflavin and its nucleotides in rat liver subcellular fractions in alloxan diabetes]. 121 Jan 79

Several components of the erythrocyte-dependent glutathione redox system (reduced glutathione, GSH; oxidized glutathione, GSSG; glutathione peroxidase, GSH-Px; glutathione reductase, GSH-Red) were determined in patients with types I and II diabetes mellitus (DM). All groups studied were male subjects: G1, 20 young healthy individuals (aged 23.7 +/- 4.2 years); G2, 15 young insulin-treated type I DM patients; G3, 20 older insulin-treated type II DM patients; G4, 21 older oral hypoglycemic agent-treated type II DM patients; G5, 28 aged healthy individuals (aged 68.9 +/- 11.5 years). There were no differences between G1 and G2, G3 or G4 regarding erythrocyte GSH, GSSG, and GSH-Red (without FAD) levels. GSH-Px activity was significantly lower in G2 when compared to G1 (15.2 +/- 4.9 vs 20.6 +/- 6.6 IU/g Hb). The GSH-Red and GSH-Px activities and GSH levels were significantly higher in G3 (4.6 +/- 1.7 IU/g Hb, 20.2 +/- 8.7 IU/g Hb and 3.5 +/- 1.3 microM/g Hb) and G4 (5.0 +/- 2.2 IU/g Hb, 16.9 +/- 6.1 IU/g Hb and 5.0 +/- 2.3 microM/g Hb) when compared to G5 (3.4 +/- 0.9 IU/g Hb, 12.0 +/- 3.6 IU/g Hb and 2.3 +/- 0.9 microM/g Hb). The findings suggest that treatment of DM can stimulate the redox activity of red blood cells in aged subjects.
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PMID:Influence of diabetes mellitus on the glutathione redox system of human red blood cells. 134 8

An acquired or inherited deficiency of FAD-linked glycerophosphate dehydrogenase activity in the pancreatic islet B-cell was recently proposed to represent a far-from-uncommon contributing factor in the pathogenesis of non-insulin-dependent diabetes mellitus. In the present study, it was investigated whether the postulated genomic defect coincides with the biosynthesis of an enzymic protein with altered catalytic properties and might concern an isoenzyme distinct from that found in extrapancreatic tissues. The activity of FAD-linked glycerophosphate dehydrogenase, as measured by either a radioisotopic or colorimetric procedure, was indeed severely decreased in islets from rats injected with streptozotocin. The intrinsic properties of the enzyme were preserved, however, as judged from the affinity for L-glycerol-3-phosphate, the ratio in reaction velocity using either FAD or iodonitrotetrazolium as electron acceptor and the activation of the enzyme by Ca2+. When the same kinetic parameters were compared in islet, liver and spleen homogenates from normal rats, significant differences were observed, however, between these three tissues, suggesting the possible existence of distinct isoenzymes.
Diabetes Res 1992
PMID:Intrinsic properties of FAD-linked glycerophosphate dehydrogenase in islets from normal and streptozotocin-induced diabetic rats. 134 98

Aldose reductase is an NADPH-dependent oxidoreductase that catalyzes the reduction of a broad range of aldehydes, including glucose. Since aldose reductase has been strongly implicated in the development of the chronic complications of diabetes mellitus, much effort has been devoted to understanding the structure and mechanism of this enzyme, and many aldose reductase inhibitors have been developed as potential drugs for the treatment of these complications. We describe here the 2.75 A crystal structure of recombinant human aldose reductase (Cys-298 to Ser mutant) complexed with NADPH. This mutant displays unusual kinetic behavior characterized by high Km/high Vmax substrate kinetics and reduced sensitivity to certain aldose reductase inhibitors. The crystal structure revealed that the enzyme is a beta/alpha-barrel with the coenzyme-binding domain located at the carboxyl-terminal end of the parallel strands of the barrel. The enzyme undergoes a large conformational change upon binding NADPH which involves the reorientation of loop 7 to a position which appears to lock the coenzyme into place. NADPH is bound to aldose reductase in an unusual manner, more similar to FAD- rather than NAD(P)-dependent oxidoreductases. No disulfide bridges were observed in the crystal structure.
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PMID:The crystal structure of the aldose reductase.NADPH binary complex. 144 21

Riboflavin excretion with urine in children suffering from diabetes mellitus is found to be significantly higher in comparison with healthy adults, the riboflavin content in the serum being normal. The total riboflavin concentration in erythrocytes is substantially lower and administration of daily-required riboflavin doses does not increase this parameter. FAD-dependent glutathione reductase in erythrocyte hemolysates is approximately 1.5 times higher than that of healthy children and does not depend on the additional intake of polyvitamins. The seeming affinity of the enzyme with exogenous FAD in sick children is almost 40 times lower in comparison with this value in healthy children, that is why the FAD-effect value in diabetes mellitus children does not exceed 1.2. Peculiarities of the riboflavin metabolism at diabetes mellitus and possibility to use the investigated parameters as criteria of vitamin B2 supply are discussed.
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PMID:[Riboflavin metabolism in diabetes mellitus]. 144 66

At 3-4 degrees C, the transport of 3-O-methyl-D-glucose (30 mM) was severely impaired in islets prepared from adult rats injected with streptozotocin during the neonatal period. However, at 37 degrees C, the first and second phase of glucose-stimulated insulin release were decreased to the same relative extent in perifused islets of diabetic, as compared to control, animals. Moreover, the time-related increase in the oxidative response of the islets to 16.7 mM D-glucose was less pronounced in diabetic than control rats. The activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase in islet homogenates of diabetic rats only represented one-fifth of that found in control rats, whereas the activity of the cytosolic NAD-glycerophosphate dehydrogenase was comparable in both types of rats. This coincided with the fact that a rise in D-glucose concentration from 2.8 to 16.7 mM failed to increase significantly L-[2-3H]glycerol conversion to 3HOH in islets from diabetic rats, in contrast to the situation found in control animals. The activity of 2-ketoglutarate dehydrogenase in islet homogenates when expressed per microgram protein was not different in control and diabetic rats. Likewise, the ratio between D-[6-14C]glucose oxidation and D-[3,4-14C]glucose oxidation and the capacity of either a non-metabolized analog of L-leucine or 3-phenylpyruvate to preferentially stimulated D-[6-14C]glucose oxidation relative to D-[5-3H]glucose utilization were both unaffected in islets from diabetic rats. These findings argue against the existence of a primary defect in the Krebs cycle of diabetic rats. It is proposed that, despite an obvious alteration of the hexose transport system in the islet cells of diabetic rats, the preferential impairment of the B-cell secretory response to D-glucose, as distinct from other secretagogues, in this model of non-insulin-dependent diabetes is mainly attributable to the low activity of FAD-linked glycerophosphate dehydrogenase, resulting in a decreased metabolic flow through the glycerol phosphate shuttle and a reduced rate of aerobic glycolysis.
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PMID:Study of hexose transport, glycerol phosphate shuttle and Krebs cycle in islets of adult rats injected with streptozotocin during the neonatal period. 153 53

In islets from adult rats injected with streptozocin during the neonatal period, the oxidative and secretory responses to D-glucose are more severely affected than those evoked by L-leucine. A possible explanation for such a preferential defect was sought by comparing the rate of aerobic glycolysis, taken as the sum of D-[3,4-14C]glucose conversion to labeled CO2, pyruvate, and amino acid, with the total glycolytic flux, as judged from the conversion of D-[5-3H]glucose to 3H2O. A preferential impairment of aerobic relative to total glycolysis was found in islets from diabetic rats incubated at either low or high D-glucose concentration. This coincided in islet mitochondria of diabetic rats with a severe decrease in both the basal (no-Ca2+) generation of 3H2O from L-[2-3H]glycerol-3-phosphate and the Ca2(+)-induced increment in [3H]glycerophosphate detritiation. The mitochondria of diabetic rats were also less efficient than those of control animals in generating 14CO2 from [1-14C]-2-ketoglutarate. The diabetes-induced alteration of 2-ketoglutarate dehydrogenase in islet mitochondria was less marked, however, than that of the FAD-linked glycerophosphate dehydrogenase and was not associated with any change in responsiveness to Ca2+. Sonicated islet mitochondria of diabetic rats displayed normal to slightly elevated glutamate dehydrogenase activity. We propose, therefore, that the preferential impairment of the oxidative and secretory responses of islet cells to D-glucose in this experimental model of diabetes may be at least partly attributable to an altered transfer of reducing equivalents into the mitochondria as mediated by the glycerol phosphate shuttle.
Diabetes 1991 Feb
PMID:Impairment of glycerol phosphate shuttle in islets from rats with diabetes induced by neonatal streptozocin. 182 72

The spiny mouse Acomys cahirinus, which exhibits beta-cell hyperplasia but low insulin secretion in captivity responded with hyperlipidemia without obesity or diabetes on a sucrose diet and became obese, and glucose-intolerant on a diet of fat-rich seeds. A three-month sucrose diet induced a marked rise in the activity of regulatory enzymes of glycolysis and lipogenesis in the liver but not in adipose tissue. There was also increased energy waste on this diet evident from a three-fold rise in the activity of hepatic mitochondrial FAD-glycerophosphate oxidase associated with an elevation in circulating triodothyronine. The obesity in mice maintained for three months on fat rich seeds was associated with moderate hyperglycemia, mild hyperinsulinemia and little change in circulating lipids. There was a decrease in the activity of glycolytic and lipogenic enzymes both in the liver and adipose tissue. Adipose tissue lipoprotein lipase activity rose, suggesting that the chylomicrons carrying the exogenous fat were better assimilated than the very-low-density lipoproteins synthesized from the dietary carbohydrate. Along with adipose tissue gain, triglyceride deposition was apparent in several muscles, accompanied by increased tissue free fatty acid, citrate and glycogen content. This suggested relation of increased muscle fat utilization with decreased glucose metabolism and insulin sensitiveness. Diverse responses to diets were thus elicited, which were particularly discernible in desert animals surviving on a limited caloric intake. Detailed follow up of these enzymatic and endocrine adaptation patterns to selective nutritional affluence may promote the understanding of the mechanisms leading to hyperlipidemia with leanness and normal glucose homeostasis versus obesity with diabetes but without hyperlipidemia.
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PMID:Intermediary metabolism during the development of obesity and diabetes in the desert rodent Acomys cahirinus. 711 67

A deficient activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase (m-GDH) in the pancreatic islet B-cell may represent a contributing factor in the pathogenesis of non-insulin-dependent (Type 2) diabetes. This enzyme controls circulation in the glycerol phosphate shuttle and, hence, plays a key role in the B-cell glucose-sensing device. An impaired activity of this enzyme in pancreatic islets was documented in several, but not all, animal models of inherited or acquired non-insulin-dependent diabetes. Enzymatic studies conducted in lymphocytes or islets from diabetic patients, as well as a search for possible mutations of the m-GDH gene, were recently undertaken to extend these observations to human subjects.
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PMID:Non-insulin-dependent diabetes mellitus and islet B-cell mitochondrial glycerophosphate dehydrogenase deficiency. 764 19

Goto-Kakizaki (GK) rat, a rodent model of spontaneously occurring non-insulin dependent diabetes mellitus (NIDDM), exhibits impaired glucose-stimulated insulin secretion. To explore the background of the beta-cell dysfunction in NIDDM, we investigated whether and how the expression pattern of factors that would potentially be involved in the glucose-stimulated insulin secretion machinery is changed in GK rats. Using quantitative reverse transcription-PCR (RT-PCR) method, we found that the gene expression of CD38, a type 2 membrane protein which has ADP-ribosyl cyclase activity, is reduced by approximately 50% in islets of GK rats. Despite previous studies showing reduction in the FAD-linked mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) activity in GK rats, the mGPDH mRNA amounts were equal to those in the control Wistar rats, suggesting a difference that arose post-transcriptionally. These observations support the idea that multiple defects of the glucose-responsive insulin secreting machinery are involved in the development of diabetes in GK rats.
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PMID:Expression of CD38 gene, but not of mitochondrial glycerol-3-phosphate dehydrogenase gene, is impaired in pancreatic islets of GK rats. 766 44


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