Protein Kinase Czeta is Required for Oleic Acid-induced Secretion of Glucagon-like Peptide-1 by Intestinal Endocrine L Cells.
From: Department of Physiology, University of Toronto, 1 King’s College Circle, Toronto, Ontario, Canada M5S 1A8.
Endocrinology
- Publish Date: Mar 2007
- ISSN: 0013-7227
- Volume: 148
- Issue: 3
- Pages: 1089-98
- Medium: Print
- Language: English
- Citation (JAMA): Iakoubov Roman, Izzo Angelo, Yeung Andrea, et al. Protein Kinase Czeta is Required for Oleic Acid-induced Secretion of Glucagon-like Peptide-1 by Intestinal Endocrine L Cells.. Endocrinology Mar 2007;148:1089-98
Abstract
Long-chain, monounsaturated fatty acids (FAs) stimulate secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1) from the intestinal L cell. Because the atypical protein kinase C (PKC), PKCzeta, is involved in FA signaling in many cells, the role of PKCzeta in FA-induced GLP-1 secretion was investigated, using the murine GLUTag L cell line and primary rat intestinal L cells. GLUTag cells expressed mRNA for several PKC isoforms, including PKCzeta, and PKCzeta protein was localized throughout the cytoplasm in GLUTag and primary L cells as well as normal mouse and rat L cells. Treatment with oleic acid (150-1000 microm) for 2 h increased GLP-1 secretion (P < 0.001), and this was abrogated by the PKCzeta inhibitor ZI (P < 0.05) and PKCzeta small interfering RNA transfection (P < 0.05) but not inhibition of classical/novel PKC isoforms. Although most PKCzeta was localized in the particulate compartment of GLUTag cells, oleate treatment did not alter PKCzeta levels or activity in this cell fraction. GLUTag cells expressed mRNA for the Gq-coupled FA receptor GPR120; however, oleic acid did not induce any changes in Akt, MAPK, or calcium, and pretreatment with LY294002 and PD98059 to inhibit phosphatidylinositol 3-kinase and MAPK, respectively, did not prevent the effects of oleic acid. Finally, GLUTag cells also released GLP-1 in response to arachidonic acid (P < 0.001) but were not affected by other long-chain FAs. These findings demonstrate that PKCzeta is required for oleic acid-induced GLP-1 secretion. This enzyme may therefore serve as a therapeutic target to enhance GLP-1 release in type 2 diabetes.
Mesh Headings (Keywords): Animals, Cells, Cultured, Embryo, Mammalian, Enteroendocrine Cells, Glucagon-Like Peptide 1, Mice, Oleic Acid, Protein Kinase C, Rats, Rats, Wistar, Tissue Distribution
Check for Full Text / PubMed Unique Identifier (PMID): 17110421
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.