Year: 2015
Type: dissertation
Abstract: Long-chain-fatty acids (LCFAs) are found in the diet, whereas short-chain fatty acids (SCFAs) are byproducts of fermentation in the distal intestine. It remains to be determined if the ileum regulates glucose production (GP). Since the GLP-1 receptor (GLP-1R) on vagal afferents is near intestinal GLP-1 secretion, receptor activation and vagal firing may mediate the effects of FAs. Intraileal LCFAs oleic acid (OA) and linoleic acid (LA), and SCFA propionate infusions decreased GP during the basal insulin-euglycemic clamp. The GP lowering effect of OA and LA required LCFA-CoA formation where the GP lowering effect of propionate was dependent on ileal GPR43 signaling, demonstrated by inhibitor co-infusion or targeted knockdown approaches, respectively. The effects of FA infusions were diminished with coinfusion of exendin-9, a GLP-1R antagonist, or tetracaine, a local anesthetic. Collectively, LCFAs and SCFA activate an ileal GLP-1R dependent neuronal network to lower GP via LCFA-CoA formation or GPR43 activation, respectively.
Source: TSpace (University of Toronto)
Author: Melika Zadeh Tahmasebi
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2781689370