Modeling K(ATP) channel gating and its regulation.
Prog Biophys Mol Biol 99:1 (2009) 7-19
Abstract:
ATP-sensitive potassium (K(ATP)) channels couple cell metabolism to plasmalemmal potassium fluxes in a variety of cell types. The activity of these channels is primarily determined by intracellular adenosine nucleotides, which have both inhibitory and stimulatory effects. The role of K(ATP) channels has been studied most extensively in pancreatic beta-cells, where they link glucose metabolism to insulin secretion. Many mutations in K(ATP) channel subunits (Kir6.2, SUR1) have been identified that cause either neonatal diabetes or congenital hyperinsulinism. Thus, a mechanistic understanding of K(ATP) channel behavior is necessary for modeling beta-cell electrical activity and insulin release in both health and disease. Here, we review recent advances in the K(ATP) channel structure and function. We focus on the molecular mechanisms of K(ATP) channel gating by adenosine nucleotides, phospholipids and sulphonylureas and consider the advantages and limitations of various mathematical models of macroscopic and single-channel K(ATP) currents. Finally, we outline future directions for the development of more realistic models of K(ATP) channel gating.A proposal of combined evaluation of waist circumference and BMI for the diagnosis of metabolic syndrome.
Endocr J 56:9 (2009) 1079-1082
Abstract:
We performed a receiver operator characteristic (ROC) curve analysis of 3915 men and 2032 women. Subjects who were diagnosed with two or more factors among high blood pressure, hyperglycaemia or high triglyceride and/or low HDL were classified as the metabolic syndrome group. By performing a ROC curve analysis, we have determined the cut-off point of waist circumference (WC) and BMI to define metabolic syndrome and further calculated the sensitivity and specificity of these two factors for the diagnosis. Cut-off point for the diagnosis of metabolic syndrome was 85 cm (men) and 80 cm (women) in WC and 24 (men) and 23 (women) in BMI. By combining these two factors, the sensitivity for the diagnosis increased to more than 80%. We conclude that it is beneficial to combine both WC and BMI for diagnosis of metabolic syndrome.A mouse model of neonatal diabetes caused by the K-ATP channel mutation Kir6.2-V59M
DIABETOLOGIA 51 (2008) S54-S54
Alpha glucosidase inhibitor voglibose can prevent pioglitazone-induced body weight gain in Type 2 diabetic patients.
Br J Clin Pharmacol 66:2 (2008) 318-319
A mutation (R826W) in nucleotide-binding domain 1 of ABCC8 reduces ATPase activity and causes transient neonatal diabetes.
EMBO Rep 9:7 (2008) 648-654