Usefulness of colon targeted DHA and EPA as novel diabetes medications that promote intrinsic GLP-1 secretion.
Glucagon-like peptide-1 (GLP-1) is a gut-derived peptide secreted from intestinal L-cells and now considered as an ideal diabetic medicine. Recently, it was reported that the unsaturated fatty acid alpha-linoleic acid promotes the secretion of GLP-1 via a G protein-coupled receptor, GPR120. However, the effects of long-chain polyunsaturated fatty acids on the secretion of GLP-1 have not been examined in vivo. The aim of this study was to evaluate the effects of the long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on blood glucose levels, plasma insulin, and GLP-1 concentrations. In addition, site-specific differences in these effects were determined using several intestinal segments: stomach, jejunum, and colon. After an intraperitoneal glucose administration (1.5 mg/g weight), each mouse was administered vehicle or an alpha-linoleic acid, DHA, EPA or EPA ester (EPA-E) solution to each intestinal segment. After an intraperitoneal glucose challenge, marked endogenous GLP-1 secretion, substantial insulin release and subsequent glucose reductions were observed in the intracolonic DHA and EPA treatment groups. In contrast, DHA and EPA did not increase GLP-1 secretion when given in the other segments. These data suggested that the colon-specific delivery of DHA, EPA, and possibly EPA-E would be a novel antidiabetic treatment by the stimulation of intrinsic GLP-1 secretion.
Morishita
Mariko
M
Department of Pharmaceutics, Hoshi University, Tokyo, Japan. morisita@hoshi.ac.jp
Tanaka
Tomohiro
T
Shida
Takayuki
T
Takayama
Kozo
K
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D019787:Linoleic Acid / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013270:Stomach / Q000187:drug effects
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D004281:Docosahexaenoic Acids; C035276:eicosapentaenoic acid ethyl ester; D052216:Glucagon-Like Peptide 1; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid