ABSTRACT
Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in pancreatic beta-cells play a crucial role in insulin secretion and glucose homeostasis. These channels are composed of two subunits: a pore-forming subunit (Kir6.2) and a regulatory subunit (sulphonylurea receptor-1). Recent studies identified large number of gain of function mutations in the regulatory subunit of the channel which cause neonatal diabetes. Majority of mutations cause neonatal diabetes alone, however some lead to a severe form of neonatal diabetes with associated neurological complications. This review focuses on the functional effects of these mutations as well as the implications for treatment.
Subject(s)
Adenosine Triphosphate , Glucose , Homeostasis , Insulin , KATP Channels , Polyphosphates , PotassiumABSTRACT
To explore the relation between the gene polymorphism of type 2 diabetes patients and their response to sulphonylurea(SU) and accomplish the personal therapy,the range of the SU pharmacogenomics should includes genes involved in the process of SU metabolism and acting,other pathological or physiological process of type 2diabetes also should be investigated,the genes recoding sulphonylurea receptor 1(SUR1),inwardly rectifying K+ channels 6.2(Kir6.2),CYP2C9 and insulin receptor substrate 1(IRS1) are the most important.
ABSTRACT
ATP sensitive potassium (K ATP ) channels widely expressed in many tissue and cell types including neurons are heteromultimers of sulfonylurea receptor (SUR) and inward rectifier K + channel (Kir6) subunits associated with 1∶1 stoichiometry as a tetramer (SUR/Kir6) 4. The activity of K ATP channels is modulated by intracellular ATP concentrations. Neuronal K ATP channels are involved in the mediation of glucose sensing and metabolic stress. Under physiological condition, they also possess important pathophysiological functions in acute brain ischemic and chronic neurodegenerative diseases.