Using pooled SNuPE, we also examined a large British Caucasian control population for the prevalence of GLUT4 Ile383, a variant which has previously been reported only in NIDDM.
The usefulness of these adaptations is illustrated by their application to the simultaneous detection of three point mutations, two in the tyrosine kinase domain of the insulin receptor and one in the insulin-responsive glucose transporter (GLUT4) in a highly insulin-resistant NIDDM population.
The discovery that glucokinase mutations can cause MODY and was also found in ten affected members of a pedigree with type 2 diabetes in which MODY had not previously been considered indicates that diagnosis based on molecular pathology will be helpful in understanding the aetiology of type 2 diabetes.
The present study does not support the hypothesis that genetic variation within the GLUT1 or GLUT4 gene loci may be responsible for familial susceptibility to Type 2 diabetes.
The present study does not support the hypothesis that genetic variation within the GLUT1 or GLUT4 gene loci may be responsible for familial susceptibility to Type 2 diabetes.
The finding of an association between polymorphic markers at the GLUT1 transporter and NIDDM suggests that this locus may contribute to the inherited susceptibility to the disease in this Italian population.
Neither inspection of individual pedigree log of odds scores nor formal tests of heterogeneity suggested a subgroup in which linkage of NIDDM and insulin-receptor gene was likely.
We conclude that genetic variation at the GLUT2 transporter gene is unlikely to contribute in a major way to the inheritance for NIDDM in this Italian population.
Taken together with recent findings in Europid and other racial groups, an abnormality of the IAPP gene is highly unlikely to represent a major gene for the development of non-insulin-dependent diabetes mellitus.
To test the hypothesis that GLUT1 and GLUT2 mutations contribute to the inherited predisposition to NIDDM, we examined linkage of these loci with NIDDM in 18 large Utah white pedigrees (two and three generation) ascertained for > or = 2 NIDDM siblings.
Linkage of GLUT1 and NIDDM was strongly and significantly rejected under all models, with total (pooled) LOD scores of -5.7 to -8.9, indicating > 500,000:1 odds against linkage.
These findings suggest that the glucokinase mutation raises the set-point of pancreatic beta cells for glucose-induced insulin secretion, leading to abnormal glucose tolerance in some patients with late-onset NIDDM.
These data do not support the view that IAPP plays an important role in the pathogenesis of NIDDM. cDNAs encoding cat, rat, mouse, guinea pig and degu IAPP precursors were also cloned, and comparison of these predicted amino acid sequences clarified the species difference, especially between amyloid-forming and non-amyloid-forming species.
This study considers the phenotypes that result from glucokinase defects and the relationship of MODY to NIDDM, and it estimates the role of glucokinase defects in NIDDM in general.
This study considers the phenotypes that result from glucokinase defects and the relationship of MODY to NIDDM, and it estimates the role of glucokinase defects in NIDDM in general.
Recently, the glucokinase gene locus on chromosome 7p has been shown to be linked to a subtype of NIDDM known as MODY in French and British pedigrees, and glucokinase mutations have been identified.
These findings suggest that mutations in or near the glucokinase gene are unlikely to be the major cause of the inherited predisposition to NIDDM in Caucasian pedigrees, but do not exclude a role for this locus with a polygenic model, or a major role in some pedigrees.
In this paper, we give a brief overview of some results for metabolic diseases (ischaemic heart disease, hypertension, subarachnoid haemorrhage, NIDDM and IDDM) using the classical twin approach in a large, unselected population-based twin cohort.
These abnormalities include low growth hormone levels in response to provocative stimuli, delayed puberty associated with prepubertal levels of gonadotropins in the males and pubertal levels of gonadotropins in the females, type II diabetes mellitus with elevated insulin levels, mild mental retardation, sensori-neural deafness, and alopecia without pili torti.