Expression of Protein Kinase C Isoforms in Pancreatic Islets and Liver of Male Goto-Kakizaki Rats, a Model of Type 2 Diabetes

Protein kinase C (PKC) is a family of protein kinases controlling protein phosphorylation and playing important roles in the regulation of metabolism. We have investigated expression levels of PKC isoforms in pancreatic islets and liver of diabetic Goto-Kakizaki (GK) rats with and without insulin treatment to evaluate their association with glucose homeostasis. mRNA and protein expression levels of PKC isoforms were assessed in pancreatic islets and liver of Wistar rats and GK rats with or without insulin treatment. PKCα and PKCζ mRNA expressions were down-regulated in islets of GK compared with Wistar rats. PKCα and phosphorylated PKCα (p-PKCα) protein expressions were decreased in islets of GK compared with insulin-treated GK and Wistar rats. PKCζ protein expression in islets was reduced in GK and insulin-treated GK compared with Wistar rats, but p-PKCζ was decreased only in GK rats. Islet PKCε mRNA and protein expressions were lower in GK compared with insulin-treated GK and Wistar rats. In liver, PKCδ and PKCζ mRNA expressions were decreased in both GK and insulin-treated GK compared with Wistar rats. Hepatic PKCζ protein expression was diminished in both GK rats with and without insulin treatment compared with Wistar rats. Hepatic PKCε mRNA expression was down-regulated in insulin-treated GK compared with GK and Wistar rats. PKCα, PKCε, and p-PKCζ expressions were secondary to hyperglycaemia in GK rat islets. Hepatic PKCδ and PKCζ mRNA expressions were primarily linked to hyperglycaemia. Additionally, hepatic PKCε mRNA expression could be under control of insulin.

蛋白激酶C（Protein kinase C, PKC）是一类调控蛋白质磷酸化的蛋白激酶家族，在代谢调控中发挥关键作用。本研究针对糖尿病Goto-Kakizaki（GK）大鼠及其经胰岛素处理的组别，探究其胰岛与肝脏组织中PKC各亚型的表达水平，以评估其与葡萄糖稳态的关联。我们分别检测了Wistar大鼠与GK大鼠（是否经胰岛素处理）的胰岛及肝脏组织中PKC亚型的mRNA与蛋白质表达水平。与Wistar大鼠相比，GK大鼠胰岛内的PKCα与PKCζ的mRNA表达量显著下调。与经胰岛素处理的GK大鼠及Wistar大鼠相比，GK大鼠胰岛中的PKCα及磷酸化PKCα（phosphorylated PKCα, p-PKCα）的蛋白质表达水平均有所降低。相较于Wistar大鼠，GK大鼠与经胰岛素处理的GK大鼠的胰岛PKCζ蛋白质表达量均出现下降，但仅GK大鼠的p-PKCζ表达量出现降低。GK大鼠胰岛的PKCε mRNA与蛋白质表达水平，均低于经胰岛素处理的GK大鼠与Wistar大鼠。在肝脏组织中，相较于Wistar大鼠，GK大鼠与经胰岛素处理的GK大鼠的PKCδ及PKCζ的mRNA表达水平均显著下降。与Wistar大鼠相比，无论是否经胰岛素处理，GK大鼠的肝脏PKCζ蛋白质表达量均明显降低。经胰岛素处理的GK大鼠，其肝脏PKCε mRNA表达水平低于未处理的GK大鼠与Wistar大鼠。GK大鼠胰岛中的PKCα、PKCε及p-PKCζ的表达变化继发于高血糖状态。肝脏中PKCδ与PKCζ的mRNA表达变化则主要与高血糖相关。此外，肝脏PKCε的mRNA表达可能受胰岛素调控。