Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Endocrine
2001 Oct 01;161:39-42. doi: 10.1385/ENDO:16:1:39.
Show Gene links
Show Anatomy links
Identification and functional analysis of mutations in FAD-binding domain of mitochondrial glycerophosphate dehydrogenase in caucasian patients with type 2 diabetes mellitus.
Gudayol M
,
Vidal J
,
Usac EF
,
Morales A
,
Fabregat ME
,
Fernández-Checa JC
,
Novials A
,
Gomis R
.
???displayArticle.abstract???
Ca2+-responsive mitochondrial FAD-linked glycerophosphate dehydrogenase (mGPDH) is a key component of the pancreatic beta-cell glucose-sensing device. The purpose of this study was to examine the association of mutations in the cDNA coding for the FAD-binding domain of mGPDH and to explore the functional consequences of these mutations in vitro. To investigate this association in type 2 diabetes mellitus, we studied a cohort of 168 patients with type 2 diabetes and 179 glucose-tolerant control subjects of Spanish Caucasian origin by single-stranded conformational polymorphism analysis. In vitro site-directed mutagenesis was performed in the mGPDH cDNA sequence to reproduce those mutations that produce amino acid changes in a patient with type 2 diabetes. We detected mutations in the mGPDH FAD-binding domain in a single patient, resulting in a Gly to Arg amino acid change at positions 77, 78, and 81 and a Thr to Pro at position 90. In vitro expression of the mutated constructs in Xenopus oocytes resulted in a significantly lower enzymatic activity than in cells expressing the wild-type form of the enzyme. Our results indicate that although mutations in the mGPDH gene do not appear to have a major role in type 2 diabetes mellitus, the reduction in mGPDH enzymatic activity associated with the newly described mGPDH mutations suggests that they may contribute to the disease in some patients.
Costa,
High prevalence of abnormal glucose tolerance and metabolic disturbances in first degree relatives of NIDDM patients. A study in Catalonia, a mediterranean community.
1998, Pubmed
Costa,
High prevalence of abnormal glucose tolerance and metabolic disturbances in first degree relatives of NIDDM patients. A study in Catalonia, a mediterranean community.
1998,
Pubmed
Eto,
Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion.
1999,
Pubmed
Fernandez-Alvarez,
Enzymatic, metabolic and secretory patterns in human islets of type 2 (non-insulin-dependent) diabetic patients.
1994,
Pubmed
Giroix,
Effects of dehydroepiandrosterone in rats injected with streptozotocin during the neonatal period.
1997,
Pubmed
Giroix,
Impairment of glycerol phosphate shuttle in islets from rats with diabetes induced by neonatal streptozocin.
1991,
Pubmed
Hanis,
A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2.
1996,
Pubmed
Lehn,
The sequence of a human mitochondrial glycerol-3-phosphate dehydrogenase-encoding cDNA.
1994,
Pubmed
MacDonald,
Single-stranded conformational polymorphism analysis of the mitochondrial glycerol phosphate dehydrogenase gene in NIDDM.
1997,
Pubmed
MacDonald,
Normalization by insulin treatment of low mitochondrial glycerol phosphate dehydrogenase and pyruvate carboxylase in pancreatic islets of the GK rat.
1996,
Pubmed
MacDonald,
Calcium activation of mitochondrial glycerol phosphate dehydrogenase restudied.
1996,
Pubmed
Malaisse,
Insulin release: the fuel hypothesis.
1979,
Pubmed
Nesher,
Interaction between genetic and dietary factors determines beta-cell function in Psammomys obesus, an animal model of type 2 diabetes.
1999,
Pubmed
Novials,
Immunodetection of mitochondrial glycerophosphate dehydrogenase (mGDH) by a polyclonal antibody raised against a recombinant mGDH fragment product.
1996,
Pubmed
Novials,
Mutation in the calcium-binding domain of the mitochondrial glycerophosphate dehydrogenase gene in a family of diabetic subjects.
1997,
Pubmed
Ostenson,
Deficient activity of FAD-linked glycerophosphate dehydrogenase in islets of GK rats.
1993,
Pubmed
Polonsky,
Seminars in Medicine of the Beth Israel Hospital, Boston. Non-insulin-dependent diabetes mellitus - a genetically programmed failure of the beta cell to compensate for insulin resistance.
1996,
Pubmed
Rasschaert,
Hexose metabolism in pancreatic islets. Glucose-induced and Ca(2+)-dependent activation of FAD-glycerophosphate dehydrogenase.
1991,
Pubmed
Rodríguez-Villar,
Effects of insulin administration on beta-cell function in subjects at high risk for type I diabetes mellitus.
1996,
Pubmed
Takeuchi,
Detection of variants in the mitochondrial glycerophosphate dehydrogenase gene in Japanese NIDDM patients.
1997,
Pubmed
Warren-Perry,
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.
1996,
Pubmed
