PKC zeta enhances insulin-like growth factor 1-dependent mitogenic activity in the rat clonal beta cell line RIN 1046-38.
Protein kinase C seems to be linked to the regulation of insulin secretion as well as mitogenic signaling in pancreatic beta cells. To study the impact of different PKC isoforms on insulin secretion and mitogenic activity we stably overexpressed the PKC isoforms alpha, beta2, epsilon, and zeta in the rat clonal beta cell line RIN 1046-38. Under basal conditions PKC alpha, beta2, epsilon, and zeta were identified mainly in the cytosol. Treatment with the phorbol ester TPA caused translocation of PKC alpha, beta2, and epsilon to the plasma membrane. Glucose- and TPA-dependent increases in insulin release were comparable in all cell lines regardless of whether PKC was overexpressed or not. While PKC isoforms alpha, beta2, and epsilon had no effect on the [(3)H]thymidine incorporation rate, overexpression of PKC zeta specifically increased basal as well as IGF-1-dependent [(3)H]thymidine incorporation. Incubation with the MAP-kinase inhibitor PD98056 abolished this effect. Furthermore, treatment with IGF-1 led to activation of the beta cell-specific transcription factor PDX-1 in RIN 1046-38 cells overexpressing PKC zeta. Our data suggest that PKC zeta is involved in basal as well as IGF-1-dependent mitogenesis in RIN 1046-38 cells, while none of the PKC isoforms tested seem to be related to glucose-stimulated insulin release.
Hennige
Anita M
AM
Department of Internal Medicine IV, University of Tübingen, Otfried-Mueller-Strasse 10, D-72076 Tübingen, Germany.
Fritsche
Andreas
A
Strack
Volker
V
Weigert
Cora
C
Mischak
Harald
H
Borboni
Patricia
P
Renn
Walter
W
Häring
Hans-Ulrich
HU
Kellerer
Monika
M
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D018398:Homeodomain Proteins; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007515:Islets of Langerhans / Q000201:enzymology; D008856:Microscopy, Fluorescence; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis; D014162:Transfection; D000099221:Protein Kinase C zeta
D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D005947:Glucose; D018398:Homeodomain Proteins; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D020033:Protein Isoforms; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine; D015534:Trans-Activators; D000099221:Protein Kinase C zeta; C084010:pancreatic and duodenal homeobox 1 protein