Epidermal growth factor increases insulin secretion and lowers blood glucose in diabetic mice.
Epidermal growth factor (EGF) is synthesized in the pancreas and diabetic animals have low levels of EGF. However, the role of EGF in regulating the major function of the pancreas, insulin secretion, has not been studied. Here, we show that EGF rapidly increased insulin secretion in mouse pancreatic islets, as well as in a pancreatic beta-cell line. These events were dependent on a Ca(2+) influx and phospholipase D (PLD) activity, particularly PLD2, as determined using pharmacological blockers and molecular manipulations such as over-expression and siRNA of PLD isozymes. In addition, EGF also increased plasma insulin levels and mediated glucose lowering in normal and diabetic mice. Here, for the first time, we provide evidence that EGF is a novel secretagogue that regulates plasma glucose levels and a candidate for the development of therapeutics for diabetes.
Lee
H Y
HY
Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
Yea
K
K
Kim
J
J
Lee
B D
BD
Chae
Y C
YC
Kim
H S
HS
Lee
D-W
DW
Kim
S-H
SH
Cho
J-H
JH
Jin
C J
CJ
Koh
D-S
DS
Park
K S
KS
Suh
P-G
PG
Ryu
S H
SH
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000097:blood / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010739:Phospholipase D / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D004815:Epidermal Growth Factor; C105606:phospholipase D2; D010739:Phospholipase D; D002118:Calcium