title: Intraduodenal milk protein concentrate augments the glycemic and food intake suppressive effects of DPP-IV inhibition.
abstract: Glucagon-like peptide-1 (GLP-1) is an incretin hormone released from intestinal L-cells in response to food entering into the gastrointestinal tract. GLP-1-based pharmaceuticals improve blood glucose regulation and may hold promise for obesity treatment, as GLP-1 drugs reduce food intake and body weight in humans and animals. In an effort to improve GLP-1 pharmacotherapies, we focused our attention on macronutrients that, when present in the gastrointestinal tract, may enhance GLP-1 secretion and improve glycemic regulation and food intake suppression when combined with systemic administration of sitagliptin, a pharmacological inhibitor of DPP-IV (enzyme responsible for GLP-1 degradation). In particular, previous data suggest that specific macronutrient constituents found in dairy foods may act as potent secretagogues for GLP-1 and therefore may potentially serve as an adjunct dietary therapy in combination with sitagliptin. To directly test this hypothesis, rats received intraperitoneal injections of sitagliptin (6 mg/kg) or saline vehicle followed by intraduodenal infusions of either milk protein concentrate (MPC; 80/20% casein/whey; 4 kcal), soy protein (nondairy control infusate; 4 kcal), or 0.9% NaCl. Food intake was assessed 30 min postinfusion. In separate studies, regulation of blood glucose was examined via a 2-h oral glucose tolerance test (2 g/kg) following identical sitagliptin treatment and intraduodenal nutrient infusions. Collectively, results show that intraduodenal MPC, but not soy protein, significantly enhances both the food intake suppression and improved control of blood glucose produced by sitagliptin. These data support the hypothesis that dietary intake of dairy protein may be beneficial as an adjunct behavioral therapy to enhance the glycemic and food intake suppressive effects of GLP-1-based pharmacotherapies.
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Diana R
authors.initials: DR
authors.lastname: Olivos
authors.forename: Lauren E
authors.initials: LE
authors.lastname: McGrath
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Turner
authors.forename: Orianne
authors.initials: O
authors.lastname: Montaubin
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Mietlicki-Baase
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hayes
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects* / Q000378:metabolism; D004435:Eating / Q000187:drug effects / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000187:drug effects* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008894:Milk Proteins / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy; D011719:Pyrazines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008894:Milk Proteins; D011719:Pyrazines; D014230:Triazoles; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate
keywords: GLP-1; dairy; diabetes; insulin; obesity