Leptin induces proliferation of pancreatic beta cell line MIN6 through activation of mitogen-activated protein kinase.
Leptin at 1-5 nM, the concentrations observed in obese subjects, caused an increase in the active form of mitogen-activated protein kinase (MAPK) that was accompanied by increased tyrosine phosphorylation of STAT-1 and STAT-3 in a mouse pancreatic beta cell line, MIN6. Leptin also increased DNA synthesis and cell viability in MIN6 cells based on the results of [3H]-thymidine incorporation and colorimetric MTT assay, respectively. The specific MAPK-inhibitor PD98059 blocked not only the MAPK activation but also the increment in DNA synthesis and cell viability caused by leptin. Thus, leptin stimulates both the MAPK and the Janus kinase (JAK)-STAT cascade as well as inducing proliferation through the MAPK cascade in MIN6 cells. This mechanism might account, at least in part, for obesity-induced pancreatic islet hypertrophy.
Tanabe
K
K
Third Department of Internal Medicine, Yamaguchi University School of Medicine, Japan.
Okuya
S
S
Tanizawa
Y
Y
Matsutani
A
A
Oka
Y
Y
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D020738:Leptin; D051379:Mice; D009765:Obesity / Q000201:enzymology / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D005419:Flavonoids; D020738:Leptin; D011506:Proteins; D015534:Trans-Activators; D014443:Tyrosine; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one