TY - JOUR
T1 - MAP kinases and their roles in pancreatic beta-cells.
AU - Khoo, Shih
AU - Gibson, Tara Beers
AU - Arnette, Don
AU - Lawrence, Michael
AU - January, Bridgette
AU - McGlynn, Kathleen
AU - Vanderbilt, Colleen A.
AU - Griffen, Steven C.
AU - German, Michael S.
AU - Cobb, Melanie H.
PY - 2004
Y1 - 2004
N2 - 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.
AB - 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.
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U2 - 10.1385/cbb:40:3:191
DO - 10.1385/cbb:40:3:191
M3 - Review article
C2 - 15289654
AN - SCOPUS:38049023139
SN - 1085-9195
VL - 40
SP - 191
EP - 200
JO - Cell biochemistry and biophysics
JF - Cell biochemistry and biophysics
IS - 3 Suppl
ER -