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Evidence for an interaction between proinsulin C-peptide and GPR146
Gina L C Yosten1, Grant R Kolar, Lauren J Redlinger
1Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 S Grand Boulevard, Saint Louis, Missouri 63104, USA. gyosten@slu.edu
The Journal of Endocrinology
|August 28, 2013
Summary
Researchers identified G protein-coupled receptor 146 (GPR146) as a key player in C-peptide signaling. This discovery advances understanding of C-peptide
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Diabetic microvascular complications like retinopathy, neuropathy, and nephropathy significantly impact patient health.
- The precise mechanisms driving diabetes-associated microvascular dysfunction remain unclear, limiting effective treatment options.
- Proinsulin C-peptide exhibits protective effects against diabetes complications, making it a promising therapeutic target.
Purpose of the Study:
- To identify the G protein-coupled receptor (GPCR) responsible for C-peptide signaling.
- To investigate the role of orphan GPCRs in mediating C-peptide's biological effects.
- To establish a foundation for developing C-peptide-based therapies.
Main Methods:
- Employed a Deductive Ligand-Receptor Matching Strategy to screen orphan GPCRs.
- Utilized gene knockdown techniques to assess the necessity of specific GPCRs (GPR146, GPR107, GPR160) for C-peptide signaling.
- Investigated C-peptide-induced cellular responses, including cFos expression and receptor internalization in KATOIII cells.
Main Results:
- Knockdown of GPR146, but not GPR107 or GPR160, abrogated C-peptide-induced cFos expression.
- C-peptide stimulation led to the internalization of GPR146.
- Observed punctate colocalization of C-peptide and GPR146 on KATOIII cell membranes, suggesting a direct interaction.
Conclusions:
- GPR146 is identified as a likely component of the C-peptide signaling complex.
- These findings provide a critical platform for further elucidation of the C-peptide signalosome.
- This research paves the way for understanding C-peptide's therapeutic potential in diabetic complications.
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