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Expression of the receptor for proinsulin C‐peptide, GPR146, in the kidney (1108.5)
Author(s) -
Redlinger Lauren,
Kolar Grant,
Samson Willis,
Yosten Gina
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1108.5
Subject(s) - proinsulin , peptide , receptor , hek 293 cells , gene knockdown , diabetic nephropathy , c peptide , kidney , medicine , biology , microbiology and biotechnology , chemistry , endocrinology , cell culture , biochemistry , diabetes mellitus , genetics
Proinsulin C‐peptide has been shown to exert protective effects in the microvasculature in both animal models of diabetes and in diabetic humans. In particular, C‐peptide may prevent or reverse diabetic nephropathy. We recently have identified the orphan G protein coupled receptor, GPR146, to be essential for C‐peptide signaling in vitro, using a Deductive Ligand‐Receptor Matching Strategy developed by our laboratory (J Endocrinology 218:B1‐8, 2013). We now report that the human embryonic kidney cell line, HEK293, responded to C‐peptide with an increase in cFos mRNA. To further evaluate the role of GPR146 in C‐peptide signaling, we employed siRNA to selectively knock down GPR146 expression in HEK293 cells and assessed the sensitivity of those cells to C‐peptide. Knockdown of GPR146 completely ablated C‐peptide‐induced cFos expression. When the neuronostatin receptor, GPR107, was selectively knocked down as a control, the response to C‐peptide was unaffected. These data support the hypothesis that GPR146 is involved in C‐peptide signaling in the kidney. The identification of GPR146 as a potential C‐peptide receptor should facilitate future studies examining the physiological relevance of C‐peptide’s action in the kidney.