Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The monomethyl ester of succinic acid (SME) was recently proposed as a novel tool for stimulation of proinsulin biosynthesis and insulin release in animal models of non-insulin-dependent diabetes mellitus. In the present study, either saline or SME (14 mmol/day) was infused for 3 days to control rats, animals injected with streptozotocin during the neonatal period, and Goto-Kakizaki rats with inherited diabetes. The infusion of SME failed to correct the anomalies found in the islets of diabetic rats, namely, a decreased activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase, a low insulin content, and an impaired secretory response to various nutrient secretagogues including D-glucose, 2-ketoisocaproate, and the combination of L-leucine and L-glutamine. These findings raise the question of whether a more prolonged administration of SME is required to raise the insulin store and improve the secretory potential of the endocrine pancreas in animals with type 2 diabetes.
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PMID:Enzymatic and secretory activities in pancreatic islets of non-insulin-dependent diabetic rats after short-term infusion of succinic acid monomethyl ester. 771 Jul 67

The aim of the present study is to compare normal and tumoral pancreatic islet cells in terms of both the activity of selected cytosolic and mitochondrial enzymes participating to nutrient catabolism and the intrinsic properties of FAD-glycerophosphate dehydrogenase. The activity of the glycolytic enzymes hexokinase and lactate dehydrogenase was higher in tumoral (RINm5F) than normal islet cells. The opposite was seen for glutamate decarboxylase, glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, glutamate dehydrogenase, 2-ketoglutarate dehydrogenase and FAD-glycerophosphate dehydrogenase (m-GDH). These findings are consistent with the high rates of glycolysis and protein synthesis seen in tumoral islet cells compared with normal islet cells, which favour mitochondrial oxidative events associated with the catabolism of D-glucose and amino acids. The intrinsic catalytic properties of m-GDH were comparable, albeit not identical, in normal and tumoral islet cells. Since a deficiency of m-GDH in pancreatic islets may represent a contributing factor in the pathogenesis of non-insulin-dependent diabetes, it is proposed that RINm5F cells may readily yield sufficient islet m-GDH for purification and further gene cloning.
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PMID:Activity of cytosolic and mitochondrial enzymes participating in nutrient catabolism of normal and tumoral islet cells. 776 86

This review reevaluates the possible roles of glut-2 underexpression, glucokinase gene mutation, glucose-6-phosphate hyperactivity, glycerophosphate dehydrogenase (FAD-linked) deficiency and glycogen accumulation in the pancreatic B-cell as contributive factors in the pathogenesis of Type 2 diabetes.
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PMID:Physiology and pathology of islet metabolism. 780 57

Impairment of glucose-induced insulin secretion in non-insulin-dependent diabetes mellitus (NIDDM) may be caused by GLUT 2 underexpression in the pancreatic beta cell, a mutation of the glucokinase gene, glucose 6-phosphatase overactivity, FAD-linked glycerophosphate dehydrogenase deficiency, a mitochondrial DNA defect and/or a secondary phenomenon of so-called glucotoxicity possibly involving glycogen accumulation in the beta-cell. It is proposed tht the methyl esters of succinic acid and related molecules may represent new tools with which to bypass these defects in glucose transport, phosphorylation and further catabolism and, hence, to stimulate both proinsulin biosynthesis and insulin release in NIDDM.
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PMID:The beta cell in NIDDM: giving light to the blind. 782 38

The mitochondrial FAD-linked enzyme glycerophosphate dehydrogenase plays a key role in the pancreatic B-cell glucose sensing device. In the present study, the activity of this enzyme was examined in islets of fa/fa rats in which inherited diabetes mellitus is associated with obesity, hyperinsulinism and severe insulin resistance. The specific activity of both FAD-linked glycerophosphate dehydrogenase and glutamate dehydrogenase were decreased in islet and liver homogenates prepared from fa/fa, as compared to Fa/Fa, rats, this coinciding with a low ratio between glutamateoxalacetate and glutamate-pyruvate transaminase activity in both islet and liver extracts, islet hyperplasia, hyperinsulinemia and hepatic steatosis in the hyperglycemic fa/fa rats. It is speculated that a low activity of FAD-linked glycerophosphate dehydrogenase in the pancreatic B-cell may participate to the perturbation of glucose homeostasis in fa/fa rats, like in other animal models of non-insulin-dependent diabetes mellitus.
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PMID:Impaired FAD-glycerophosphate dehydrogenase activity in islet and liver homogenates of fa/fa rats. 783 41

This study aimed to compare the metabolic and secretory responses of pancreatic islets from animals with non-insulin-dependent diabetes to D-glucose with the effects of the methyl esters of succinic acid (SME) and glutamic acid (GME). The insulin secretory response to D-glucose was impaired in islets from rats with diabetes which was either inherited (Goto-Kakizaki (GK) rats) or acquired (streptozotocin-treated (STZ) rats). This coincided with a preferential alteration of oxidative relative to total glycolysis in intact islets and a selective defect of FAD-linked mitochondrial glycerophosphate dehydrogenase (m-GDH) in islet homogenates. This enzymatic defect was also found in purified B cells from STZ rats. It contrasted both with unaltered activities of glutamate dehydrogenase and succinate dehydrogenase in the islets of diabetic animals and with a normal or even increased activity of m-GDH in the livers of GK and STZ rats. The oxidation of [1,4-14C]SME and [U-14C]GME appeared decreased in islets of GK or STZ animals when compared with control rats, but no significant difference between control and diabetic rats was observed when the oxidative data were expressed relative to the rate of [U-14C]GME hydrolysis. Nevertheless, the absolute values for insulin release evoked by a non-metabolized analogue of L-leucine (BCH), by SME and by the association of BCH with either SME or GME were invariably lower in islets of GK and STZ rats than in those of control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pancreatic islet response to dicarboxylic acid esters in rats with type 2 diabetes: enzymatic, metabolic and secretory aspects. 784 32

Measurements of blood and liver water-soluble vitamins and of their metabolites urinary excretion helped characterize these vitamins metabolism in rats with streptozotocin-induced diabetes. The liver levels of recovered ascorbic acid and total thiamin were virtually the same in diabetic and intact rats. Essential changes of riboflavin metabolism were revealed in diabetes: riboflavin urinary excretion was five times higher than that in intact animals, the blood serum levels being the same in health and disease, whereas liver riboflavin levels in diabetic rats had a trend to lowering. The activities of FAD-dependent hepatic enzymes were the same in both groups. 4-pyridoxylic acid excretion was increased and 1-methylnicotinamide excretion reduced in diabetic rats.
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PMID:[Water-soluble vitamin metabolism in rats with streptozotocin-induced diabetes]. 805 81

Islets were isolated by automatic digestion from non-diabetic cadaveric organ donors and from Type 2 (non-insulin-dependent) diabetic subjects. The activity of FAD-glycerophosphate dehydrogenase, but not that of either glutamate dehydrogenase, glutamate-oxalacetate transaminase or glutamate-pyruvate transaminase, was lower in Type 2 diabetic patients than control subjects. Hexokinase, glucokinase and glutamate decarboxylase activities were also measured in islets from control subjects. The utilization of D-[5-3H]glucose, oxidation of D-[6-14C]glucose and release of insulin evoked by D-glucose were all lower in Type 2 diabetic patients than control subjects. The secretory response to the combination of L-leucine and L-glutamine appeared less severely affected. Islets from Type 2 diabetic patients may thus display enzymatic, metabolic and secretory anomalies similar to those often observed in animal models of Type 2 diabetes, including a deficiency of beta-cell FAD-linked glycerophosphate dehydrogenase, the key enzyme of the glycerol phosphate shuttle.
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PMID:Enzymatic, metabolic and secretory patterns in human islets of type 2 (non-insulin-dependent) diabetic patients. 816 52

In 12 out of 32 non-insulin-dependent diabetic subjects, the activity of FAD-linked glycerophosphate dehydrogenase in T lymphocyte homogenates was abnormally low when measured by both a colorimetric and radioisotopic procedure. A comparable situation characterized by a deficient activity of FAD-linked glycerophosphate dehydrogenase in both the colorimetric and radioisotopic assays was only observed once among 26 other subjects including 11 healthy volunteers, 9 non-diabetic patients, 5 type-1 (insulin-dependent) diabetics, and 1 pancreatectomized diabetic. By analogy, it is speculated that an impaired activity of FAD-linked glycerophosphate dehydrogenase in the insulin-producing pancreatic B-cell could represent a far-from-uncommon contributive factor in the pathogenesis of non-insulin-dependent diabetes mellitus.
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PMID:Could non-insulin-dependent diabetes mellitus be attributable to a deficiency of FAD-linked glycerophosphate dehydrogenase? 826 Jan 99

In 35 children of 9-13 years old with insulin-dependent diabetes mellitus distinct alterations in metabolism of vitamin B2 were detected, which were manifested as elevated rate of riboflavin excretion with urine and a decrease in the vitamin content in erythrocytes, as 1.5-fold increase in activity of erythrocyte glutathione reductase and augmented affinity of erythrocyte glutathione reductase to exogenous FAD. Alterations in metabolism of riboflavin did not involve the vitamin deficiency as shown by analysis of vitamins B6 and PP (4-pyridoxic acid and I-methyl nicotinamide, respectively) excretion with urine as well as by study of the coenzymes content in blood of healthy and sick children with various rates of riboflavin consumption. Rates of 4-pyridoxic acid and I-methyl nicotinamide excretion with urine were similar both in healthy children of 9-13 years and in children of this age with diabetes mellitus. The data obtained suggest that rates of riboflavin consumption in patients with diabetes mellitus differed from those of healthy persons; these reasons should be taken into consideration in evaluation of vitamins B2 consumption in patients with diabetes mellitus.
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PMID:[Metabolism of riboflavin and B group vitamins functionally bound to it in insulin-dependent diabetes mellitus]. 827 39


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