Free fatty acids administered into the colon promote the secretion of glucagon-like peptide-1 and insulin.
We examined whether free fatty acids (FFAs) promote glucagon-like peptide-1 (GLP-1) secretion when administered into the intestinal tract. We found that an unsaturated long-chain FFA, alpha-linolenic acid (alpha-LA), resulted in increased plasma GLP-1 and insulin levels when administered into the colon. Such stimulatory effects were not apparent with either vehicle or a saturated middle-chain FFA, octanoic acid (OA). Concomitant with GLP-1 secretion, the administration of alpha-LA, but not vehicle or OA, also resulted in a significant increase in the population of pERK positive cells within the GLP-1 positive cells of the colonic mucosa. Moreover, colonic administration of alpha-LA into normal C3H/He mice caused a reduction in plasma glucose levels, as well as in type 2 diabetic model NSY mice. Our results indicate that the in vivo colonic administration of alpha-LA promotes secretion of incretin GLP-1 by activating the ERK pathway in L-cells and thereby enhances the secretion of insulin.
Adachi
Tetsuya
T
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Tanaka
Toshiki
T
Takemoto
Kazuhisa
K
Koshimizu
Taka-aki
TA
Hirasawa
Akira
A
Tsujimoto
Gozoh
G
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004750:Enteral Nutrition; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage / Q000493:pharmacokinetics*; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D052216:Glucagon-Like Peptide 1