And here's one for Lyndacarol about Kv1.3 and insulin.
A new variant in the human Kv1.3 gene is associated with low insulin sensitivity and impaired glucose tolerance.
J Clin Endocrinol Metab. 2006 Feb;91(2):654-8.
Tschritter O, Machicao F, Stefan N, Schafer S, Weigert C, Staiger H, Spieth C, Haring HU, Fritsche A.
Medizinische Universitatsklinik, Otfried-Muller-Strasse 10, D-72076 Tubingen, Germany.
CONTEXT: The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed in a variety of tissues including liver and skeletal muscle. In animal models, knockout of Kv1.3 has been found to improve insulin sensitivity and glucose tolerance.
OBJECTIVE: We examined whether mutations in the Kv1.3 gene exist in humans and whether they are associated with alterations of glucose homeostasis.
DESIGN AND SETTING: We conducted a genotype-phenotype association study at a university hospital.
PARTICIPANTS AND METHODS: In 50 nondiabetic subjects, we screened approximately 4.5 kb of chromosome 1 comprising the single exon, the promoter/5'-untranslated region, and the 3'-untranslated region of the human Kv1.3 gene for mutations by direct sequencing. Subsequently, all identified single-nucleotide polymorphisms were analyzed in 552 nondiabetic subjects who underwent an oral glucose tolerance test (OGTT). Of these, 304 had undergone an additional hyperinsulinemic euglycemic clamp.
MAIN OUTCOME MEASURES: We assessed postprandial blood glucose during OGTT and insulin sensitivity measured by hyperinsulinemic euglycemic clamp.
RESULTS: We identified five single-nucleotide polymorphisms in the promoter region (T-548C, G-697T, A-845G, T-1645C, and G-2069A) with allelic frequencies of the minor allele of 26, 23, 9, 41, and 16%, respectively. The -1645C allele was associated with higher plasma glucose concentrations in the 2-h OGTT (P = 0.03) even after adjustment for sex, age, and body mass index (P = 0.002). In addition, it was associated with lower insulin sensitivity (P = 0.01, adjusted for sex, age, and body mass index). Functional in vitro analysis using EMSA showed differential transcription factor binding to the T-1645C polymorphism.
CONCLUSIONS: We show that a variant in the promoter of the Kv1.3 gene is associated with impaired glucose tolerance and lower insulin sensitivity. Therefore, the Kv1.3 channel represents a candidate gene for type 2 diabetes.