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.