Showing papers by "Stephen O'Rahilly published in 1989"

Analysis of the HepG2/erythrocyte glucose transporter locus in a family with type 2 (non-insulin-dependent) diabetes and obesity.

Abstract: A recent report has shown an association between a specific Xba1 restriction fragment of the human HepG2-Erythrocyte glucose transporter gene and Type 2 (non-insulin dependent) diabetes. To further examine the significance of this finding we have studied Type 2 diabetic pedigrees for linkage between the Xba1 alleles of this glucose transporter gene and diabetes. One large pedigree, in which the diabetic phenotype was associated with obesity and insulin resistance, was informative. In this family the disease did not co-segregate with the glucose transporter locus. Formal linkage analysis was performed assuming autosomal dominant inheritance with age-dependent penetrance. At putative gene frequencies of 0.01 and 0.001 the logarithin of the odds for linkage versus non-linkage at a recombination fraction of 0.001 was −1.84 and −3.32 respectively (a value of <-2 indicates definite non-linkage). Genetic variations in the HepG2-Erythrocyte glucose transporter gene are unlikely to be responsible for the development of diabetes in this pedigree.

Analysis of the pro-opiomelanocortin gene in non-insulin dependent diabetic families.

Abstract: Products of the pro-opiomelanocortin gene have been shown to have marked effects on insulin secretion. Selective antagonists of beta-endorphin have been reported to correct the impaired insulin secretory response to glucose seen in non-insulin dependent diabetes. Families with an autosomal dominant pattern of inheritance of diabetes were studied for possible linkage between diabetes and the pro-opiomelanocortin locus by examining the inheritance of a Rsa 1 restriction fragment length polymorphism. In two families with classical Type 2 diabetes there were recombinants between the disease and the pro-opiomelanocortin locus. In a family with maturity-onset diabetes of the young there were only two informative meoises, but there was a crossover between the disease and the pro-opiomelanocortin gene locus. Inherited defects in or near the pro-opiomelanocortin gene locus are unlikely to be directly involved in the aetiology of non-insulin dependent diabetes.