Diabetes & Metabolism Journal

Original Articles

Polymorphisms of Kir6.2 Gene are Associated with Type 2 Diabetes and Blood Pressure in the Korean Population.: Bo Kyeong Koo, Hong Il Kim, Eu Jin Lee, Young Min Cho, Hyoung Doo Shin, Hak Chul Jang, Hong Kyu Lee, Kyong Soo Park; Korean Diabetes J. 2005;29(5):440-450. Published online September 1, 2005

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Abstract PDF: BACKGOUND: ATP-sensitive potassium channels are a heterooctamer of SUR1 and Kir6.2, which are key components in the insulin secretory mechanism. Whether common variants in the Kir6.2 gene are associated with type 2 diabetes and/or its associated phenotypes was investigated. METHODS: The Kir6.2 gene was sequenced in 24Korean DNA samples to identify common polymorphisms (frequency > 0.05). The common variants found among these samples were genotyped in a larger population including type 2 diabetic patients and nondiabetic subjects. RESULTS: Thirteen single nucleotide polymorphisms and one insertion/deletion polymorphism were identified in the Kir6.2 gene, with six common variants(g.-1709A>T, g.-1525T>C, g.67G >A [E23K], g.570C>T [A190A], g.1009A>G [1337V], and g.1388C>T) genotyped in 761 type 2 diabetic patients and 675 nondiabetic subjects. Four individual polymorphisms(g.-1525T > C, g.67G>A, g.1009A>G and g.1388C>T) appeared to be associated with type 2 diabetes (age, sex and BMI-adjusted odds ratio[OR]=0.751[0.584-0.967] in the recessive model on g-1525T>C, 1.193 [1.020-1.394] in the additive model in g.67G>A, 1.195 [1.022-1.399] in the additive model on g.1009A>G, 0.835 [0.717-0.973] in the additive model in g.1388C >T). The haplotype "ATACGC" in the Kir6.2 gene, composed of rare allele in the g.67 and g.1009, was also associated with a higher prevalence of type 2 diabetes (age, sex, and BMI- adjusted OR = 1.256 [1.067-1.479], P for logistic regression = 0.006). In addition g.67G>A and g.1009A >G in the KCNJ11 were strongly associated with a high systolic blood pressure. CONCLUSION: Polymorphisms in the Kir6.2 gene are associated with type 2 diabetes and blood pressure in the Korean population.

A Differential Effect of Intracellular ATP on Skeletal-and Smooth Muscle-Type KATP Channel Activities.: Oh Dae Kwon, Jeong Geun Lim, Haeng Gyun Kim, Dae Kwang Kim, Jae Seok Hwang, Keun Gyu Park, Sung Hee Park, Chi Heum Cho, In Kyu Lee, Dae Kyu Song; Korean Diabetes J. 2003;27(4):332-342. Published online August 1, 2003

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Abstract PDF: BACKGROUND
The ATP-sensitive potassium (KATP) channel comprises an inwardly- rectifying K+ channel (Kir) and a sulfonylurea receptor(SUR). This study investigated the mechanism of different ATP sensitivity between skeletal-(Kir6.2/SUR2A) and smooth muscle- (Kir6.2/SUR2B) type KATP channels. METHODS: Messenger RNAs encoding mouse Kir6.2, and rat SUR2A or 2B were co-injected into Xenopus Laevis oocytes to express each type of KATP channel. Using the inside-out patch clamp technique, the channel currents for MgATP sensitivity were measured and analyzed. RESULTS: By addition of 100 microM of MgATP, the current initially decreased and then slowly increased in Kir6.2/SUR2A. This gradual, ATP sensitivity decrease during prolonged MgATP application was totally blocked by LY 294002, a pho- sphatidylinositol-3 and -4 kinase inhibitor. In contrast, a rather rapid sensitivity decrease after initial inhibition was observed in Kir6.2/SUR2B by 100 microM of ATP, which was not blocked by LY 294002. This channel activation was Mg2+- dependent, suggesting that ATP hydrolysis is critical. CONCLUSION: This result supports the idea that the ability of MgATP to stimulate Kir6.2/SUR2B channels reflects a faster rate of ATP hydrolysis at NBD2 of SUR2B.

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