Effect Of Simvastatin On ATP-sensitive K⁺Channels And L-type Ca²⁺ Channels Of Mouse Pancreatic Beta Cells

Research backgroundStatins can reduce serum cholesterol, stabilize atherosclerotic plaque, anti-inflammatory and antioxidation, ameliorating vascular endothelium and so on, they play an important role in clinical practice. However, more and more clinical evidences indicate that statins are able to increase the incidence of new-onset diabetes in recent years.And type2diabete is a risk equivalent condition for coronary and peripheral arterial diseases, these findings create a paradox as to statins’representative of the strongest cardiovascular risk reduction tool. So statins increase the risk of new-onset diabetes and its possible mechanism has drawn extensive attention from medicine scholars. This study applied the whole-cell patch clamp technology to abserve the effect of simvastatin on electrophysiology of mouse pancreatic beta cell line Min6.ObjectiveTo observe the effect of lipid-lowering drug simvastatin on the current of ATP-sensitive potassium Channels and L-type calcium Channels of mouse pancreatic beta cell Min6cells. These studies can further provide new laboratory evidences of the effect on sugar metabolism of statins in the clinical applications and could provide better advices about it.MethodMin6cells were divided into0.05%dimethyl sulfoxide (DMSO) group, normal control group and low-concentration, middle-concentration, high-concentration simvastatin treatment groups, which were cultured last for48hours with high concentration glucose DMEM containing10%fetal bovine serum plus0.05%dimethylsulfoxide,0,2,5and10μmol/L simvastatin, respectively. Whole-cell patch clamp technology was used to record the current of ATP-sensitive potassium Channels and L-type calcium Channels of Min6cells.ResultThe mean potassium current density of normal external solution perfusion group was92.81±4.10pA/pF, and after added diazoxide and glibenclamide to external solution, respectively, it increased to250.75±20.86pA/pF(P<0.01)and decreased to31.07±1.82pA/pF(P<0.01),respectively. When it contained16.7mmol/L glucose in external solution, the mean potassium current density attenuated to51.48±7.40pA/pF(P<0.01).Compared with normal control group,2,5and10μmol/L simvastatin treatment markedly enhanced the current density of ATP-sensitive potassium Channels,the mean amplitude reached to117.94±3.67pA/pF,153.91±12.38pA/pF,307.01±6.40pA/pF(P<0.01), respectively. As to L-type calcium Channels, the current density was-21.03±0.55pA/pF and decreased to1.08±0.36pA/pF(P<0.01) in glucose external solution group and glibenclamide intervened group, respectively.Compared with the former, the current density of2,5and10umol/L simvastatin drug treatment groups decreased to-16.31±0.51pA/pF,-10.75±0.71pA/pF,-3.30±0.46pA/pF(P<0.01),respectively.ConclusionSimvastatin probably inhibits insulin secretion and glycometabolism in mouse pancreatic beta cell line Min6via enhances the current density of ATP-sensitive potassium Channels and inhibits the current density of L-type calcium Channels.