C-terminal part of AgRP stimulates insulin secretion through calcium release in pancreatic beta Rin5mf cells.
Agouti-related protein (AgRP) is an orexigenic peptide which is composed of three parts; the amino (N)-terminus, the middle part, and the carboxyl (C)-terminus. AgRP has been implicated in various cell signaling, but the precise role of each parts are currently unclear. In this study, we have attempted to determine which part of AgRP was critical for insulin secretion. We have found that the C-terminus of AgRP specifically increases the intracellular calcium concentration in pancreatic beta Rin5mf cells in a PLC-dependent manner, whereas the middle part and C-terminus have little effects on calcium release. This calcium response can be observed in the freshly isolated primary beta cells also. Moreover, amperometric measurement reveals that the C-terminus of AgRP increases the rate of exocytosis in Rin5mf cells. We further show that this region of AgRP is responsible for insulin secretion in a PLC-dependent manner. Taken together, these results indicate that the C-terminus of AgRP can participate in the insulin secretion in pancreatic beta cells, through the modulation of calcium release.
Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, San31 Hyoja-Dong Nam-Gu Pohang, Kyungbuk 790-784, South Korea.
Hyeon Soo
HS
Kim
Sanatombi
S
Yumkham
Hye-Young
HY
Lee
Jung-Hwa
JH
Cho
Mean-Hwan
MH
Kim
Duk-Su
DS
Koh
Sung Ho
SH
Ryu
Pann-Ghill
PG
Suh
D054369:Agouti-Related Protein; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D036341:Intercellular Signaling Peptides and Proteins; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism
C515198:AGRP protein, human; D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D011506:Proteins; C411703:agouti-related protein-(83-132); D010738:Type C Phospholipases; D002118:Calcium