The pivotal role of protein kinase C zeta (PKCzeta) in insulin- and AMP-activated protein kinase (AMPK)-mediated glucose uptake in muscle cells.
Insulin and AMP-activated protein kinase (AMPK) signal pathways are involved in the regulation of glucose uptake. The integration of signals between these two pathways to maintain glucose homeostasis remains elusive. In this work, stimulation of insulin and berberine conferred a glucose uptake or surface glucose transporter 4 (GLUT4) translocation that was less than simple summation of their effects in insulin-sensitive muscle cells. Using specific inhibitors to key kinases of both pathways and PKCzeta small interference RNA, protein kinase C zeta (PKCzeta) was found to regulate insulin-stimulated protein kinase B (PKB) activation and inhibit AMPK activity on dorsal cell surface. In the presence of berberine, PKCzeta controlled AMPK activation and AMPK blocked PKB activity in perinuclear region. The inhibition effect of PKCzeta on AMPK activation or the arrestment of PKB activity by AMPK still existed in basal condition. These results suggest that there is antagonistic regulation between insulin and AMPK signal pathways, which is mediated by the switch roles of PKCzeta.
Liu
Li-Zhong
LZ
Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity, Li Ka Shing Institute of Health, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, N.T., Hong Kong, China.
Cheung
Stanley C K
SC
Lan
Lin-Lin
LL
Ho
Stanley K S
SK
Chan
Juliana C N
JC
Tong
Peter C Y
PC
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001599:Berberine / Q000494:pharmacology; D001692:Biological Transport; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D000099221:Protein Kinase C zeta
D055372:AMP-Activated Protein Kinases; D001599:Berberine; D004791:Enzyme Inhibitors; D005947:Glucose; D007328:Insulin; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D000099221:Protein Kinase C zeta