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题名:GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and regulates somatostatin secretion from murine islets of Langerhans.
作者:STONE VM; DHAYAL S; BROCKLEHURST KJ; LENAGHAN C; SORHEDE WINZELL M; HAMMAR M; XU X; SMITH DM; MORGAN NG;
来源:Diabetologia. 2014 Mar 25. [ IF= 6.49 ] ]
URL :10.1007/s00125-014-3213-0
日期:20140408
摘要:AIMS/HYPOTHESIS: The NEFA-responsive G-protein coupled receptor 120 (GPR120) has
been implicated in the regulation of inflammation, in the control of incretin
secretion and as a predisposing factor influencing the development of type 2
diabetes by regulation of islet cell apoptosis. However, there is still
considerable controversy about the tissue distribution of GPR120 and, in
particular, it remains unclear which islet cell types express this molecule. In
the present study, we have addressed this issue by constructing a
Gpr120-knockout/beta-galactosidase (LacZ) knock-in (KO/KI) mouse to examine the
distribution and functional role of GPR120 in the endocrine pancreas. METHODS: A
KO/KI mouse was generated in which exon 1 of the Gpr120 gene (also known as
Ffar4) was replaced in frame by LacZ, thereby allowing for regulated expression
of beta-galactosidase under the control of the endogenous GPR120 promoter. The
distribution of GPR120 was inferred from expression studies detecting
beta-galactosidase activity and protein production. Islet hormone secretion was
measured from isolated mouse islets treated with selective GPR120 agonists.
RESULTS: beta-galactosidase activity was detected as a surrogate for GPR120
expression exclusively in a small population of islet endocrine cells located
peripherally within the islet mantle. Immunofluorescence analysis revealed
co-localisation with somatostatin suggesting that GPR120 is preferentially
produced in islet delta cells. In confirmation of this, glucose-induced
somatostatin secretion was inhibited by a range of selective GPR120 agonists.
This response was lost in GPR120-knockout mice. CONCLUSIONS/INTERPRETATION: The
results imply that GPR120 is selectively present within the delta cells of murine
islets and that it regulates somatostatin secretion.

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