title: Administration of pioglitazone alone or with alogliptin delays diabetes onset in UCD-T2DM rats.
abstract: There is a need to identify strategies for type 2 diabetes prevention. Therefore, we investigated the efficacy of pioglitazone and alogliptin alone and in combination to prevent type 2 diabetes onset in UCD-T2DM rats, a model of polygenic obese type 2 diabetes. At 2 months of age, rats were divided into four groups: control, alogliptin (20 mg/kg per day), pioglitazone (2.5 mg/kg per day), and alogliptin+pioglitazone. Non-fasting blood glucose was measured weekly to determine diabetes onset. Pioglitazone alone and in combination with alogliptin lead to a 5-month delay in diabetes onset despite promoting increased food intake and body weight (BW). Alogliptin alone did not delay diabetes onset or affect food intake or BW relative to controls. Fasting plasma glucose, insulin, and lipid concentrations were lower and adiponectin concentrations were threefold higher in groups treated with pioglitazone. All treatment groups demonstrated improvements in glucose tolerance and insulin secretion during an oral glucose tolerance test with an additive improvement observed with alogliptin+pioglitazone. Islet histology revealed an improvement of islet morphology in all treatment groups compared with control. Pioglitazone treatment also resulted in increased expression of markers of mitochondrial biogenesis in brown adipose tissue and white adipose tissue, with mild elevations observed in animals treated with alogliptin alone. Pioglitazone markedly delays the onset of type 2 diabetes in UCD-T2DM rats through improvements of glucose tolerance, insulin sensitivity, islet function, and markers of adipose mitochondrial biogenesis; however, addition of alogliptin at a dose of 20 mg/kg per day to pioglitazone treatment does not enhance the prevention/delay of diabetes onset.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, T7 022A Veterinary Research Tower (Box 17), Ithaca, New York 14850, USA Department of Molecular Biosciences, School of Veterinary Medicine Department of Nutrition, University of California Davis, Davis, California, USA Department of Internal Medicine, University of California, Davis, Sacramento, California, USA.
authors.forename: Bethany P
authors.initials: BP
authors.lastname: Cummings
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bettaieb
authors.forename: James L
authors.initials: JL
authors.lastname: Graham
authors.forename: Kimber
authors.initials: K
authors.lastname: Stanhope
authors.forename: Fawaz G
authors.initials: FG
authors.lastname: Haj
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Havel
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000378:metabolism; D008297:Male; D000077205:Pioglitazone; D010880:Piperidines / Q000008:administration & dosage*; D051381:Rats; D045162:Thiazolidinediones / Q000008:administration & dosage*; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; D045162:Thiazolidinediones; D014498:Uracil; C520853:alogliptin; D000077205:Pioglitazone
keywords: alogliptin; islet; pioglitazone; type 2 diabetes