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)

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 thyroidectomized rats, the activity of FAD-linked glycerophosphate dehydrogenase was severely diminished in liver homogenates but not affected significantly in pancreatic islet homogenates, whilst the activity of 2-ketoglutarate dehydrogenase was decreased modestly in both liver and islet homogenates. Likewise, in intact islets of thyroidectomized rats, the generation of 3HOH from [2-3H]glycerol was not decreased, and the ratio between oxidative and total glycolysis not significantly lower than in islets from sham-operated rats, at least in the presence of a high concentration of D-glucose. Nevertheless impaired oxidation of both D-[3,4-14C]glucose and D-[6-14C]glucose was observed in islets of thyroidectomized rats, the relative magnitude of such a decrease being more pronounced at a low than at a high D-glucose concentration. Such metabolic anomalies coincided with a lower level of plasma insulin and decreased output of insulin by islets incubated at low (2.8 mM), but not higher, concentrations of D-glucose. It is concluded that hypothyroidism does not mimic the deficiency in islet FAD-linked glycerophosphate dehydrogenase activity found in rats with inherited or acquired non-insulin-dependent diabetes.
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PMID:Enzymatic, metabolic and secretory perturbations in pancreatic islets of thyroidectomized rats. 832 84

The mitochondrial enzyme FAD-linked glycerophosphate dehydrogenase (m-GDH) is thought to play a key role in the glucose-sensing mechanism of the insulin-producing B-cell. It catalyses a rate-limiting step of the glycerol phosphate shuttle in pancreatic islets. Its activation by Ca2+ accounts for the preferential stimulation of oxidative glycolysis and, hence, pyruvate oxidation in glucose-stimulated islets. Reduced activity of m-GDH was recently observed in islet, but not liver, homogenates from rats injected with streptozotocin during the neonatal period and in two models of inherited diabetes, i.e. GK rats and db/db mice. In the streptozotocin-injected and GK rats the m-GDH islet defect coincided, in intact islets, with an abnormally low ratio between oxidative and total glycolysis. Decreased activity of m-GDH in T-lymphocytes was also observed in 12 of 32 type 2 (non-insulin-dependent) diabetic patients, but only once among 26 other subjects including 11 healthy volunteers, 9 non-diabetics and 6 patients with either type 1 (insulin-dependent) or symptomatic diabetes. In the T-lymphocytes of type 2 diabetics the m-GDH deficiency occasionally coincided with an abnormally high ratio between glutamate-pyruvate and glutamate-oxaloacetate transaminase activities, as also observed in islets from streptozotocin-injected or GK rats. It is speculated that an islet m-GDH defect could represent a far from uncommon factor contributing to the pathogenesis of type 2 diabetes mellitus.
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PMID:Is type 2 diabetes due to a deficiency of FAD-linked glycerophosphate dehydrogenase in pancreatic islets? 832 24

In vitro, streptozotocin (1.0-2.0 mM) fails to exert any immediate effect on the activity of FAD-glycerophosphate dehydrogenase in either pancreatic islet homogenate or freshly isolated intact islets. However, when injected in vivo, streptozotocin (40 mg/kg body weight) lowers the specific activity of the FAD-linked enzyme in islet homogenates within 24 h, whilst causing little change in 2-ketoglutarate dehydrogenase and increasing glutamate dehydrogenase islet activity. In animals which became frankly hyperglycaemic as the result of the injection of streptozotocin, the activity of islet FAD-glycerophosphate dehydrogenase, measured 2 weeks after administration of the B-cell cytotoxic agent, was decreased to 10-20% of its control value. Neither insulin treatment nor riboflavin supplementation affected this enzymic defect. Even when the animals injected with streptozotocin remained virtually euglycaemic, the activity of islet FAD-glycerophosphate dehydrogenase was markedly decreased. This coincided with a preferential impairment of aerobic glycolysis, as judged from the ratio between D-[3,4-14C]glucose oxidation and D-[5-3H] glucose utilization by the islets. It is proposed, therefore, that the administration of sub-diabetogenic amounts of streptozotocin to adult rats represents an alternative and easier approach to the study of B-cell dysfunction in this model of type 2 (non-insulin-dependent) diabetes than does streptozotocin injection in neonatal rats.
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PMID:Streptozotocin-induced FAD-glycerophosphate dehydrogenase suppression in pancreatic islets. Relationship with the severity and duration of hyperglycaemia and resistance to insulin or riboflavin treatment. 832 33

The activity of FAD-linked glycerophosphate dehydrogenase (m-GDH), as well as that of glutamate dehydrogenase and both glutamate-oxalacetate and glutamate-pyruvate transaminases, were measured in islet, liver, and splenocyte homogenates from 6- to 7-week-old female nonobese diabetic mice (NOD) and age- and sex-matched control mice. Despite incipient insulitis and euglycemia, the NOD mice displayed both high islet insulin content and elevated insulinemia. The activity of m-GDH, expressed relative to protein content, was not decreased in islets of NOD mice, despite the fact that such a specific activity is lower in splenic lymphocytes than islet cells. In liver homogenates, the activity of m-GDH was even higher in NOD than control mice. It is proposed, therefore, that in this model of insulin-dependent diabetes no primary decrease in islet m-GDH activity occurs, at variance with the situation recently documented in several animal models of non-insulin-dependent diabetes.
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PMID:FAD-linked glycerophosphate dehydrogenase activity in islets, liver, and splenocytes of NOD mice. 837 36

In pancreatic islet extracts of rats with hereditary non-insulin-dependent diabetes mellitus (GK rats), the activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase, as measured by either a radioisotopic or colorimetric procedure, only represented 30 to 40% of that found in control rats. This decrease in enzymic activity was not attributable to any sizeable change in either islet DNA content or the relative contribution of insulin-producing beta cells to total islet mass. It contrasted with a normal activity of other mitochondrial dehydrogenases and hexokinase isoenzymes. It coincided, however, with an increased activity of glutamate-pyruvate transaminase, as already observed in adult rats injected with streptozotocin during the neonatal period. The decreased activity of islet FAD-linked glycerophosphate dehydrogenase also contrasted with an increased activity of the same enzyme in the liver of GK, as compared to control rats. In the light of these findings and recent metabolic data collected in intact islets of GK rats, it is proposed that a deficiency of beta-cell FAD-linked glycerophosphate dehydrogenase, the key enzyme of the glycerol phosphate shuttle, may represent a cause of inherited non-insulin-dependent diabetes.
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PMID:Deficient activity of FAD-linked glycerophosphate dehydrogenase in islets of GK rats. 840 39

The mitochondrial enzyme FAD-linked glycerophosphate dehydrogenase plays a key role in the glucose-sensing device of the insulin-producing pancreatic B-cell. Its activity was found to be decreased in islet, but not liver, homogenates of BL/Ks-db/db mice, in which diabetes mellitus represents an inherited disease. The decreased activity of FAD-linked glycerophosphate dehydrogenase contrasted with a normal activity of glutamate dehydrogenase and 2-ketoglutarate dehydrogenase in the islets of db/db mice. It is proposed that a site-specific defect of FAD-linked glycerophosphate dehydrogenase in the pancreatic B-cell might represent a far-from-uncommon causal or contributing factor in the pathogenesis of non-insulin-dependent diabetes mellitus.
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PMID:FAD-linked glycerophosphate dehydrogenase deficiency in pancreatic islets of mice with hereditary diabetes. 842 47

In several animal models of non-insulin-dependent diabetes, a decreased activity of FAD-linked glycerophosphate dehydrogenase was recently documented in pancreatic islet, but not liver, homogenates. The present study reveals that, on the contrary, the activity of the same mitochondrial enzyme is increased in islet, but not liver or spleen, homogenates of BB, as compared to BW, rats examined before the onset of severe hyperglycemia in this animal model of autoimmune insulin-dependent diabetes.
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PMID:Increased activity of FAD-linked glycerophosphate dehydrogenase in pancreatic islets of BB rats. 849 19

Two genes that have potentially important regulatory roles in insulin secretion are both located on chromosome 2q24.1. G-protein-coupled muscarinic potassium channel (GIRK1) is an inwardly rectifying K+ channel that helps to maintain the resting potential and excitability of cells. Mitochondrial FAD-linked glycerophosphate dehydrogenase (m-GDH) catalyzes a rate-limiting step of the glycerol phosphate shuttle in pancreatic islets. Reduced m-GDH activity has been demonstrated in islets isolated from diabetic subjects compared with islets from nondiabetic control subjects and from the diabetic GK rat. To study the relationship between these candidate genes and NIDDM, we have examined a simple tandem-repeat polymorphism (STRP) close to both the KCN J3 (GIRK1) locus and the m-GDH locus. In a linkage study of three maturity-onset diabetes of the young (MODY) pedigrees, not linked to MODY1, MODY2, or MODY3, a cumulative score of - 9.6 at a recombination fraction of theta = 0 excluded linkage. In a population-association study, no linkage disequilibrium for the STRP was found between 190 unselected NIDDM patients and 60 geographically and age-matched white nondiabetic subjects (chi2 = 1.51 on 3 df, P = 0.68). Thus, mutations involving the genes for GIRK1 or FAD-glycerophosphate dehydrogenase are unlikely to cause MODY, and a common mutation in either gene is unlikely to contribute to NIDDM in whites. These data do not exclude mutations in some families or other ethnic groups.
Diabetes 1996 May
PMID:Mitochondrial FAD-glycerophosphate dehydrogenase and G-protein-coupled inwardly rectifying K+ channel: No evidence for linkage in maturity-onset diabetes of the young or NIDDM. 862 Oct 16


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