Targeted disruption of glycogen synthase kinase-3β in cardiomyocytes attenuates cardiac parasympathetic dysfunction in type 1 diabetic Akita mice.

ABSTRACT: Type 1 diabetic Akita mice develop severe cardiac parasympathetic dysfunction that we have previously demonstrated is due at least in part to an abnormality in the response of the end organ to parasympathetic stimulation. Specifically, we had shown that hypoinsulinemia in the diabetic heart results in attenuation of the G-protein coupled inward rectifying K channel (GIRK) which mediates the negative chronotropic response to parasympathetic stimulation due at least in part to decreased expression of the GIRK1 and GIRK4 subunits of the channel. We further demonstrated that the expression of GIRK1 and GIRK4 is under the control of the Sterol Regulatory element Binding Protein (SREBP-1), which is also decreased in response to hypoinsulinemia. Finally, given that hyperactivity of Glycogen Synth

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC6461277 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature