Abstract

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.

Highlights

  • Type 2 Diabetes (T2D) is a heterogeneous disorder characterized by chronic hyperglycaemia

  • At day 0, the body weights in GK rats (246 ± 3) and GK rats with insulin treatment (255 ± 5 g) were lower compared with Wistar rats (337 ± 7 g, p < 0.001 for both) (Fig 1A)

  • After the 14-day treatment period, the body weights increased in Wistar rats (401 ± 9 g, p < 0.001) and GK rats with insulin treatment (287 ± 3 g, p < 0.01) compared with the respective control at day 0 (337 ± 7 g and 255 ± 5 g, respectively)

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Summary

Introduction

Type 2 Diabetes (T2D) is a heterogeneous disorder characterized by chronic hyperglycaemia. The aetiological heterogeneity is suggested by genetic inheritance and its interplay with environmental factors. The most important pathophysiological features are impaired insulin secretion and decreased insulin sensitivity (insulin resistance), the latter related to the liver and extrahepatic tissues, mainly skeletal muscle and adipose tissue [1,2,3,4]. PKC in Pancreatic Islets and Liver vr.se, The Swedish Diabetes Association, i.e. the Diabetes Fund (to CGÖ); www.sdf.se, and the Karolinska Institutet Fund (to HFG, and to CGÖ); www.ki.se. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials

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