Doxycycline Prevents Preclinical Atherosclerosis, Pancreatic Islet Loss and Improves Insulin Secretion after Glycemic Stimulation: Preclinical Study in Individuals with a High-Fat Diet

强力霉素可预防临床前动脉粥样硬化、胰岛损失并改善血糖刺激后的胰岛素分泌:针对高脂饮食个体的临床前研究

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作者:Alejandrina Rodriguez-Hernandez, Marina Delgado-Machuca, Rodolfo Guardado-Mendoza, Martha A Mendoza-Hernandez, Valery Melnikov, Osiris G Delgado-Enciso, Daniel Tiburcio-Jimenez, Gabriel Ceja-Espiritu, Gustavo A Hernandez-Fuentes, Armando Gamboa-Dominguez, Jose Guzman-Esquivel, Margarita L Martinez-F

Abstract

Doxycycline (Doxy) is an antibiotic, which has exhibited anti-inflammatory activity and glucose metabolism improvement. The present study was proposed to evaluate its effects on glucose metabolism and other associated processes, such as lipemia and adipogenesis, as well as, to evaluate its effects on the liver, pancreas, and aorta in subjects fed with an occidental high-fat diet (HFD). The trial followed three groups of BALB/c mice for 6 months: (1) Standard diet (SD); (2) HFD-placebo (saline solution); and (3) HFD-Doxy (10 mg/kg/day). Intrahepatic fat accumulation (steatohepatosis) and the epididymal fat pad, as well as the hepatic inflammatory infiltrate and ALT serum levels were higher in both groups with the HFD (with/without doxycycline) in comparison with the SD group. The thickness of the aorta (preclinic atherosclerosis) was significantly elevated in the HFD group with respect to the HFD + Doxy and SD group, these two being similar groups to each other. The HFD-Doxy group had pancreatic morphological parameters very similar to those of the SD group; on the contrary, the HFD group reduced the number of pancreatic islets and the number of β cells per mm2, in addition to losing large islets. The index of β cell function (∆Insulin0-30/∆Glucose0-30 ratio) was significantly higher in the HFD + Doxy group, compared to the rest of the groups.

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