title: Colonic delivery of docosahexaenoic acid improves impaired glucose tolerance via GLP-1 secretion and suppresses pancreatic islet hyperplasia in diabetic KK-A(y) mice.
abstract: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates the insulin secretion depending on blood glucose level. Recent studies show that the unsaturated fatty acids can promote GLP-1 secretion from intestinal L-cells. We have shown previously that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) administered into a mouse closed intestinal loop, especially into the colonic segment, stimulate GLP-1 and insulin secretion and have a hypoglycemic effect, suggesting that DHA and EPA have potential as antidiabetic agents. The present study examined the antidiabetic effect of DHA following long-term in vivo delivery to the colon using normal ddY and diabetic KK-A(y) mice. The plasma GLP-1 concentration of KK-A(y) mice increased after long-term DHA administration, and this had a significant hypoglycemic effect. In contrast, although GLP-1 secretion in ddY mice tended to increase after DHA administration, blood glucose concentration did not differ between vehicle- and DHA-treated ddY mice. Immunostaining of the pancreas after long-term DHA administration showed that continuous DHA treatment stimulated β-cell apoptosis and accordingly suppressed islet cell growth in KK-A(y) mice. Colon targeting of DHA may provide a new strategy for improving impaired glucose tolerance in type 2 diabetes mellitus by stimulating GLP-1 secretion, which may subsequently suppress the compensatory hyperplasia of pancreatic islets.
authors.affiliation: Ono Pharmaceutical Co., Ltd., 1-8-2 Kyutaro-machi, Chuo-ku, Osaka-shi, Osaka 541-8564, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shida
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Kamei
authors.forename: Mariko
authors.initials: M
authors.lastname: Takeda-Morishita
authors.forename: Koichi
authors.initials: K
authors.lastname: Isowa
authors.forename: Kozo
authors.initials: K
authors.lastname: Takayama
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003106:Colon / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004281:Docosahexaenoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006965:Hyperplasia / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D004281:Docosahexaenoic Acids; D052216:Glucagon-Like Peptide 1