title: Combining sitagliptin/metformin with a functional fiber delays diabetes progression in Zucker rats.
abstract: Our primary objective was to determine whether administering the viscous and fermentable polysaccharide PolyGlycopleX (PGX) with metformin (MET) or sitagliptin/metformin (S/MET) reduces hyperglycemia in Zucker diabetic fatty (ZDF) rats more so than monotherapy of each. Glucose tolerance, adiposity, satiety hormones and mechanisms related to dipeptidyl peptidase 4 activity, gut microbiota and, hepatic and pancreatic histology were examined. Male ZDF rats (9-10 weeks of age) were randomized to: i) cellulose/vehicle (control, C); ii) PGX (5% wt/wt)/vehicle (PGX); iii) cellulose/metformin (200  mg/kg) (MET); iv) cellulose/S/MET (10  mg/kg+200  mg/kg) (S/MET); v) PGX (5%)+MET (200  mg/kg) (PGX+MET); vi) cellulose/sitagliptin/MET (5%)+(10  mg/kg+200  mg/kg) (PGX+S/MET) for 6 weeks. PGX+MET and PGX+S/MET reduced glycemia compared with C and singular treatments (P=0.001). Weekly fasted and fed blood glucose levels were lower in PGX+MET and PGX+S/MET compared with all other groups at weeks 4, 5, and 6 (P=0.001). HbA1c was lower in PGX+S/MET than C, MET, S/MET, and PGX at week 6 (P=0.001). Fat mass was lower and GLP1 was higher in PGX+S/MET compared with all other groups (P=0.001). β-cell mass was highest and islet degeneration lowest in PGX+S/MET. Hepatic lipidosis was significantly lower in PGX+S/MET compared with PGX or S/MET alone. When combined with PGX, both MET and S/MET markedly reduce glycemia; however, PGX+S/MET appears advantageous over PGX+MET in terms of increased β-cell mass and reduced adiposity. Both combination treatments attenuated diabetes in the obese Zucker rat.
authors.affiliation: Faculty of Kinesiology Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, 2500 University Drive Northwest, Calgary, Alberta, Canada T2N 1N4 Product Safety Labs, Department of Pharmacology, Dayton, New Jersey, USA Department of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, New Jersey, USA Factors Group of Nutritional Companies, Inc. R&D, 3655 Bonneville Place, Burnaby, British Columbia, Canada Canadian Centre for Functional Medicine, 1552 United Boulevard, Coquitlam, British Columbia, Canada University of British Columbia, Food, Nutrition and Health Program, Vancouver, British Columbia, Canada.
authors.forename: Raylene A
authors.initials: RA
authors.lastname: Reimer
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Grover
authors.forename: Lee
authors.initials: L
authors.lastname: Koetzner
authors.forename: Roland J
authors.initials: RJ
authors.lastname: Gahler
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lyon
authors.forename: Simon
authors.initials: S
authors.lastname: Wood
mesh_terms: D000464:Alginates / Q000008:administration & dosage*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018450:Disease Progression; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage*; D011719:Pyrazines / Q000008:administration & dosage*; D051381:Rats; D011924:Rats, Zucker; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D000464:Alginates; D001786:Blood Glucose; D004338:Drug Combinations; D007004:Hypoglycemic Agents; C540519:PolyGlycoplex; D011135:Polysaccharides, Bacterial; D011719:Pyrazines; D014230:Triazoles; D008687:Metformin; D000068900:Sitagliptin Phosphate
keywords: DPP4 inhibitor; PolyGlycopleX; diabetes medication; glycemia; obesity