Signaling through the p38 and p42/44 Mitogen-Activated Families of Protein Kinases in Pancreatic β-Cell Proliferation

Abstract

The present study has focused on the role of the 42- and 44-kDa mitogen-activated protein kinases (p42/44 MAPKs) and the 38-kDa mitogen-activated protein kinase (p38 MAPK) in the proliferation of the pancreatic β-cell line MIN6. MIN6 β-cell proliferation was assessed by measuring 5-bromo-2′-deoxyuridine (BrdU) incorporation into cellular DNA. Inhibition of both the p42/44 MAPK pathway using the MEK inhibitor PD098059 (PD) and the p38 MAPK pathway using the p38 inhibitor SB203580 (SB) caused a marked, concentration-dependent reduction in the BrdU immunostaining observed in the presence of 15% FCS when assessed using fluorescence immunocytochemistry. These data provide direct evidence of a role for p42/44 MAPKs in the mitogenic response of MIN6 β-cells to FCS. Furthermore, these data also suggest a novel role for the p38 MAPK pathway in MIN6 β-cell proliferation.