Absence of the β1 subunit of AMP‐activated protein kinase reduces myofibroblast infiltration of the kidneys in early diabetes

摘要

Activation of the heterotrimeric energy‐sensing kinase ‐activated protein kinase ( ) has been reported to improve experimental diabetic kidney disease. We examined the effect of type 1 diabetes in wild‐type ( ) mice and mice lacking the β1 subunit of ( β1 mice), which have reduced activity in kidneys and other organs. Diabetes was induced using streptozotocin ( ) and the animals followed up for 4 weeks. Hyperglycaemia was more severe in diabetic β1 mice, despite the absence of any difference in serum levels of insulin, adiponectin and leptin. There was no change in activity in the kidneys of diabetic mice by activity assay, or phosphorylation of either the αT172 activation site on the α catalytic subunit of or the ‐specific phosphosite S79 on acetyl CoA carboxylase 1 ( 1). Phosphorylation of the inhibitory αS485 site on the α subunit of was significantly increased in the diabetic mice compared to non‐diabetic controls. Despite increased plasma glucose levels in the diabetic β1 mice, there were fewer myofibroblasts in the kidneys compared to diabetic mice, as evidenced by reduced α‐smooth muscle actin (α‐ ) protein by Western blot, by ‐ and fewer α‐ ‐positive cells by immunohistochemical staining. Albuminuria was also reduced in the β1 mice. In contrast to previous studies, therefore, myofibroblasts were reduced in the kidneys of β1 diabetic mice compared to diabetic mice, despite increased circulating glucose, suggesting that can worsen renal fibrosis in type 1 diabetes.