Protein kinase Cδ but not PKCα is involved in insulin‐induced glucose metabolism in hepatocytes

Abstract

The liver is a major insulin-responsive tissue responsible for glucose regulation. One important mechanism in this phenomenon is insulin-induced glycogen synthesis. Studies in our laboratory have shown that protein kinase Cs delta (PKCδ) and alpha (α) have important roles in insulin-induced glucose transport in skeletal muscle, and that their expression and activity are regulated by insulin. Their importance in glucose regulation in liver cells is unclear. In this study we investigated the possibility that these isoforms are involved in the mediation of insulin-induced glycogen synthesis in hepatocytes. Studies were done on rat hepatocytes in primary culture and on the AML-12 (alpha mouse liver) cell line. Insulin increased activity and tyrosine phosphorylation of PKCδ within 5 min. In contrast, activity and tyrosine phosphorylation of PKCα were not increased by insulin. PKCδ was constitutively associated with IR, and this was increased by insulin stimulation. Suppression of PKCδ expression by transfection with RNAi, or overexpression of kinase dead (dominant negative) PKCδ reduced both the insulin-induced activation of PKB/Akt and the phosphorylation of glycogen synthase kinase 3 (GSK3) and reduced significantly insulin-induced glucose uptake. In addition, treatment of primary rat hepatocytes with rottlerin abrogated insulin-induced increase in glycogen synthesis. Neither overexpression nor inhibition of PKCα appeared to alter activation of PKB, phosphorylation of GSK3 or glucose uptake in response to insulin. We conclude that PKCδ, but not PKCα, plays an essential role in insulin-induced glucose uptake and glycogenesis in hepatocytes.

Corneal Wound Healing, a Newly Identified Function of CAP37, Is Mediated by Protein Kinase C Delta (PKCδ)

“…15 Others have shown a surprisingly fast increase of PKCd transcription and translation in muscle cells within a few minutes of insulin treatment. 33 In our experiments the induction of PKCd was not transient and persisted up to 18 hours after CAP37 treatment (Fig. 5).…”

Modulation of Insulin Sensitivity of Hepatocytes by the Pharmacological Downregulation of Phospholipase D

“…Non- 14 C-labeled hepatocytes were used to study insulin-induced uptake of 2-D-[ 3 H]glucose (0.5 μ Ci/mL) and incorporation of D-[U 14 C]glucose (0.1 μ Ci/mL) into glycogen by the method of Brutman-Barazani et al [ 27 ]. Cells were washed free from the additions in the HBS buffer (HEPES-buffered saline) containing 20 mM HEPES.…”

Pingyang Jiangya Fang pretreatment reduces the blood pressure of spontaneously hypertensive rats with Liver-Yang hyperactivity syndrome via ROS/Akt oxidative stress pathway

“…Notably, high glucose concentration causes skeletal muscle damage. On the other hand, nutrients are delivered to target organs by regulating microvascular nutrition, including cardio cerebral renal and neurovascular units (22,23). Hypertension is a state of oxidative stress, resulting in the generation of excessive reactive oxygen.…”