MAP kinases and their roles in pancreatic beta-cells.
We discuss our work examining regulation and functions of mitogen-activated protein kinases, particularly ERK1 and ERK2, in pancreatic beta-cells. These enzymes are activated by glucose, other nutrients, and insulinogenic hormones. Their activation by these agents is calcium-dependent. A number of other stimuli also activate ERK1/2, but by mechanisms distinct from those involved in nutrient sensing. Inhibition of ERK1/2 has no apparent effect on insulin secretion measured after 2 h. On the other hand, ERK1/2 activity is required for maximal glucose-dependent activation of the insulin gene promoter. The primary effort has focused on INS-1 cell lines, with supporting and confirmatory studies in intact islets and other beta-cell lines, indicating the generality of our findings in beta-cell function. Thus ERK1/2 participate in transmitting glucose-sensing information to beta-cell functions. These kinases most likely act directly and indirectly on multiple pathways that regulate beta-cell function and, in particular, to transduce an elevated glucose signal into insulin gene transcription.
Khoo
Shih
S
Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
Gibson
Tara Beers
TB
Arnette
Don
D
Lawrence
Michael
M
January
Bridgette
B
McGlynn
Kathleen
K
Vanderbilt
Colleen A
CA
Griffen
Steven C
SC
German
Michael S
MS
Cobb
Melanie H
MH
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D010703:Phorbol Esters / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D014158:Transcription, Genetic
D004791:Enzyme Inhibitors; D007328:Insulin; D010703:Phorbol Esters; D000242:Cyclic AMP; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002118:Calcium