title: Pancreatic ultrastructural enhancement due to telmisartan plus sitagliptin treatment in diet-induced obese C57BL/6 mice.
abstract: OBJECTIVE
  We sought to evaluate the effects of telmisartan, sitagliptin, or their combination on pancreatic ultrastructural alterations in high-fat-fed C57BL/6 mice.
  
  
  METHODS
  Three-month-old C57BL/6 mice were fed with standard chow (SC, 10% lipids) or high-fat diet (HF, 60% lipids) during 10 weeks to induce obesity and its comorbidities. After this period, treatment began (lasted 6 weeks), and the HF group was divided into 4 subgroups: untreated HF, HF plus telmisartan (5 mg/kg per day), HF plus sitagliptin (1.1 g/kg per day), and HF plus telmisartan plus sitagliptin. Drugs were mixed with diet. Biochemical analyses, radioimmunoassay, immunofluorescence, stereology, and transmission electron microscopy were performed to assess pancreatic remodeling.
  
  
  RESULTS
  Overweight, hyperinsulinemia, hyperglycemia, and dyslipidemia were found in the HF group, but these outcomes were controlled by the different treatments. Untreated HF animals also showed alterations concerning distribution of α/β cell followed by large and numerous lipid droplets within pancreas. Telmisartan and sitagliptin as monotherapy alleviated these findings, and a complete reversal of pancreatic steatosis was observed after treating with the combination of the 2 drugs.
  
  
  CONCLUSIONS
  AT1 receptor blockade, partial peroxisome proliferator-activated receptor gamma activation, and extended incretin action emerge as feasible strategies to control pancreatic steatosis and avoid progression of pancreatic diseases due to lipotoxicity.
authors: Laboratory of Morphometry, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Vanessa
authors: V
authors: Souza-Mello
authors: Bianca M
authors: BM
authors: Gregório
authors: Bernardo
authors: B
authors: Relvas-Lucas
authors: Tatiane
authors: T
authors: da Silva Faria
authors: Marcia Barbosa
authors: MB
authors: Aguila
authors: Carlos Alberto
authors: CA
authors: Mandarim-de-Lacerda