Combined therapy with metformin and insulin attenuates systemic and hepatic alterations in a model of high‐fat diet‐/streptozotocin‐induced diabetes

In this study we have explored the pathogenesis of the hepatic alterations which occur in diabetes and the modulation of these complications by the combination of metformin adjunct treatment and insulin monotherapy. For this purpose, diabetic rats were treated with insulin (DM + Ins) or metformin plus insulin (DM + Met + Ins). Biochemical and cardiometabolic parameters were analysed by spectrophotometry. Intravital microscopy was used to study the hepatic microcirculation. In the liver tissue, real‐time PCR was used to analyse oxidative stress enzymes, inflammatory markers and receptors for advanced glycation end products (AGE) (RAGE) gene expression. Lipid peroxidation was assessed by thiobarbituric acid reactive species (TBARs) analyses. AGE deposition and RAGE protein expression were studied by fluorescence spectrophotometry and Western blot respectively. Body weight, %HbA1c, urea, total proteins and oxidative stress parameters were found to be similarly improved by insulin or Met + Ins treatments. On the other hand, Met + Ins treatment showed a more pronounced effect on fasting blood glucose level than insulin monotherapy. Fructosamine, uric acid, creatinine, albumin and amylase levels and daily insulin dose requirements were found to be only improved by the combined Met + Ins treatment. Liver, renal and pancreatic dysfunction markers were found to be more positively affected by metformin adjunct therapy when compared to insulin treatment. Liver microcircula...

Source: International Journal of Experimental Pathology - July 5, 2016 Category: Pathology Authors: Raquel Rangel Silvares, Evelyn Nunes Goulart da Silva Pereira, Edgar Eduardo Ilaquita Flores, Vanessa Estato, Patrícia Alves Reis, Igor José da Silva, Marcelo Pelajo Machado, Hugo Caire de Castro Faria Neto, Eduardo Tibiriça, Anissa Daliry Tags: Original Article Source Type: research