J A Maassen

..Furthermore, it contributes to damage the pancreatic beta-cells. Ultimately, this situation results in the development of a hyperglycemic state...

..Furthermore, the clinical presentation of the disease is summarized as are the methods to detect the A3243G mutation, particular in view of the often low levels of heteroplasm of the A3243G mutation...

..Furthermore, MODY2 patients generally have a milder clinical course and fewer complications than MODY3 patients, who consequently require a more aggressive therapeutic approach...

..This observation supports the hypothesis that during embryogenesis mitochondrial DNA goes through a genetic bottleneck with a limited number of segregating units...

..These disease states highlight the critical contribution of the carbohydrate flux through glycolysis and mitochondria and its coupling to ATP production in determining insulin secretion...

..This situation may contribute to the development of particular phenotypes that are associated with distinct mtDNA mutations...

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..As a result, mutations in mtDNA can deregulate multiple processes within cells and the balance of this deregulation may contribute to the clinical phenotype...

..The underlying mechanisms and variability in clinical presentation are discussed...

..As a consequence, a systemic overload with fatty acids occurs, leading to an enhanced decline in beta-cell function due to lipotoxicity...

..Enhanced aging of pancreatic beta-cells, a reduced capacity of these cells to synthesize large amounts of insulin,and a resetting of the ATP/ADP-regulated K-channel seem to be the pathogenic factors involved...

..Thus, the number and activity of mitochondria within adipocytes contribute to the threshold at which fatty acids are released into the circulation, leading to insulin resistance and type 2 diabetes...

..To discuss the role of mitochondria in the development of type 2 diabetes...

..A sustained increased phosphorylation of the serine/threonine kinases p70S6kinase and Jun N-terminal kinase in the absence of insulin may underlie the abrogated phosphorylation of the IRS proteins and their downstream targets...

..This results in an impaired ability of insulin to stimulate glycogen synthesis...

..We assessed whether polymorphisms in the glucocorticoid receptor gene NR3C1 associate with measures of β-cell function and insulin sensitivity derived from hyperglycaemic clamps in subjects with normal or impaired glucose tolerance...

..The ability of the Ser412 mutant to bind insulin in cross-linking experiments suggests that the impaired transport of the proreceptor to the cell surface is the primary cause for the binding defect to intact cells...

..These observations suggest that the level of IRS-1 phosphorylation rather than the level of IRS-2 phosphorylation mediates insulin-induced glycogen synthesis and DNA synthesis in 3T3-L1 pre-adipocytes...

..Approximately 1.3% of insulin-dependent diabetic patients in the Netherlands has this mutation. The main defect in these patients seems to be a reduced secretion of insulin by the pancreas in response to glucose stimulation...

..The aim of the present study was to estimate the heritability of the beta cell insulin response to glucose and to glucose combined with glucagon-like peptide-1 (GLP-1) or with GLP-1 plus arginine...

..Phenotypic expression of MIDD includes Type 1-like and Type 2-like diabetes. This study examined whether HLA-DQ phenotype and the degree of heteroplasmy in leucocyte and oral mucosa DNA influence clinical expression of the 3242 mutation...

..We examined activation of mTOR-signalling in relation to insulin resistance and hepatic steatosis in mice...

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..Genome-wide association studies have recently identified novel type 2 diabetes susceptibility gene regions. We assessed the effects of six of these regions on insulin secretion as determined by a hyperglycaemic clamp...

..We estimated the heritability of individual differences in beta cell function after a mixed meal test designed to assess a wide range of classical and model-derived beta cell function parameters...

..In this study we examined whether these loci also contribute to type 2 diabetes susceptibility...

..These findings demonstrate that the primary genetic lesion in Seip-Berardinelli's lipodystrophy is outside the insulin receptor gene and that an involvement of the insulin-like growth factor I receptor is also unlikely...

..The mutation for the first time characterizes a region in the insulin receptor which seems to be involved in transmitting the insulin binding signal to the tyrosine kinase domain...

..0%). However, this association did not achieve genome-wide levels of significance. The aim of this study was to establish the true contribution of this variant and common variants in LARS2 (MAF > 5%) to type 2 diabetes risk...

..58; 95% CI 2.87-20.03, P<0.001) in the obese but not in the nonobese subjects. The results indicate that obesity may be a pivotal factor in multiplying the disease risk associated with the Leu7Pro polymorphism in preproNPY...

..To describe the results of mutation analysis of the genes involved in maturity onset diabetes of the young (MODY) types 1-3...

..The large regional differences in allele frequency of the Arg972 allele of IRS-1 gene makes genetic association studies of this gene less reliable...

..The present study suggests an important role of the simultaneous production of IGF-II and IGFBP-6 in the pathophysiology of tumour-induced hypoglycaemia...

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..We conclude that the decrease in the relative amount of the A isoform in these patients is probably an epiphenomenon due to impaired insulin action...

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..This may be responsible for some of the insulin-mimicking effects of hyperosmolarity. The activation of stress kinases by hyperosmolarity occurs independent of the IR...

..The possible mechanisms underlying the pathogenesis of mitochondrial diabetes is discussed...

..In rats, exposure to excessive alimentary fat, inducing a type 2 diabetic phenotype, may result in myocardial insulin resistance and cardiac functional changes resembling DCM...

..Though the precise mechanism by which Ras is converted to the GTP bound state remains to be established, a tight correlation exists between receptor autophosphorylation and Ras-GTP formation...

..However, empirical data, often based on small samples, did not confirm this observation in all studies. Therefore, the role of mtDNA content in T2D remains elusive...

..Secondly, to investigate whether these cellular parameters can predict the growth response to GH treatment in children with ISS...

..The mutation seems to alter the conformation of the receptor in such way that the transport of the proreceptor to the Golgi compartment, where proteolytical processing occurs, is inhibited...

..72). In conclusion, we did not find evidence for association of common variants in 13 nuclear-encoded mitochondrial proteins with T2DM...