NIDDM--genetic marker; glucose transporter, glucokinase, and mitochondria gene.
Candidate genes for NIDDM have been screened in Japanese. Mutations in the glucokinase gene were found in apparent late-onset NIDDM patients as well as in MODY patients. Clinical characteristics in the subjects with glucokinase gene mutations are similar to those in Caucasian subjects; diabetes mellitus is generally mild and some patients actually remain as having impaired glucose tolerance. Of great interest is that all affected subjects show blunted insulin secretion response to the glucose challenge, which is most commonly observed in Japanese NIDDM patients. Thus, it is possible that impairment in the regulation of glucokinase gene expression or its enzyme activity is associated with at least some Japanese NIDDM patients, though the prevalence of the mutations in the coding region is relatively low. In contrast, a mitochondrial tRNA(Leu(UUR)) gene mutation at np 3243 appears to be much more common, and diabetes due to this mutation has a progressive nature. Insulin secretory capacity progressively decreases, eventually reaching an insulin-dependent state in most patients. A surprising result is that this gene mutation is often observed in ICA-positive IDDM patients who were initially non-insulin-dependent, so called slowly progressive IDDM patients. These results suggest that the mitochondrial gene mutation may cause beta cell loss in addition to defects in glucose-induced signaling in pancreatic beta cells, which explains that the mitochondrial gene mutation manifests a wide range of diabetic phenotypes, from NIDDM to IDDM.
Oka
Y
Y
Third department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
D044466:Asian People / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005819:Genetic Markers; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000097:blood; D007564:Japan / Q000453:epidemiology; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009154:Mutation
D004272:DNA, Mitochondrial; D005819:Genetic Markers; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D005941:Glucokinase