Document Detail

Essential Role for Protein Kinase C{zeta} in Oleic Acid-Induced Glucagon-Like Peptide-1 Secretion in Vivo in the Rat.
MedLine Citation:
PMID:  21325047     Owner:  NLM     Status:  Publisher    
Luminal monounsaturated long-chain fatty acids [e.g. oleic acid (OA)] increase secretion of the incretin, glucagon-like peptide-1 (GLP-1) from the ileocolonic L cell. However, it is not known whether OA ingestion causes a sufficient increase in distal luminal concentrations to directly enhance GLP-1 secretion. Furthermore, we have demonstrated that protein kinase Cζ (PKCζ) is required for OA-induced GLP-1 secretion in vitro; however, the physiological relevance of this finding remains unknown. Therefore, we have determined luminal OA concentrations in OA-fed rats and examined the effects of direct OA stimulation on GLP-1 secretion using a novel model of intestinal-specific PKCζ knockdown. Murine GLUTag L cells express numerous fatty acid transport proteins and take up OA in a saturable manner. Oral administration of OA increased the ileal chyme content of OA by 140-fold over 60-120 min (P < 0.05-0.01), peaking at 105 ± 50 μmol/g. To evaluate the direct effects of OA on GLP-1 secretion, 125 mm OA was rectally infused into the colon and terminal ileum of rats. Plasma bioactive GLP-1 increased from 20 ± 6 to 102 ± 21 pg/ml at 60 min (P < 0.01). However, pretreatment with ileocolonic adenoviral PKCζ small interfering RNA resulted in a 68 ± 8 reduction in the GLP-1 response to rectal OA (P < 0.001). The results of these studies indicate that OA levels in the rat terminal gut after oral ingestion are sufficient to induce GLP-1 secretion and that PKCζ is necessary for the effects of OA on GLP-1 secretion in vivo. PKCζ may therefore serve as a novel therapeutic target to enhance GLP-1 levels in patients with type 2 diabetes.
Roman Iakoubov; Ausma Ahmed; Lina M Lauffer; Richard P Bazinet; Patricia L Brubaker
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-15
Journal Detail:
Title:  Endocrinology     Volume:  -     ISSN:  1945-7170     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Departments of Physiology (R.I., A.A., L.M.L., P.L.B.), Nutritional Sciences (R.P.B.), and Medicine (P.L.B.), University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich 81675, Germany (R.I.); and Department of Medicine, Campus Innenstadt, Ludwig-Maximilians-Universität München, Munich 80336, Germany (L.M.L.).
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