Effects of metformin on insulin resistance and metabolic disorders in tumor-bearing rats with advanced cachexia

Metformin (MET) is widely used in the correction of insulin (INS) resistance and metabolic abnormalities in type 2 diabetes. However, its effect on INS resistance and metabolic disorders associated with cancer cachexia is not established. We investigated the MET effects, isolated or associated with INS, on INS resistance and metabolic changes induced by Walker-256 tumor in rats with advanced cachexia. MET (500 mg.kg-1, oral) and MET + INS (NPH, 1.0 IU.kg-1, sc) were administered during 12 days, starting on the day of tumor cell inoculation. Tumor-bearing rats showed adipose and muscle mass wasting, weight loss, anorexia, decreased Akt phosphorylation in retroperitoneal and mesenteric adipose tissue, peripheral INS resistance, hypoinsulinemia, reduced INS content and secretion from pancreatic islets and also inhibition of glycolysis, gluconeogenesis and glycogenolysis in liver. MET and MET + INS treatments did not prevent these changes. It can be concluded that treatments with MET and MET + INS did not prevent the adipose and muscle mass wasting and weight loss of tumor-bearing rats possibly by not improving INS resistance. Therefore, MET, used for the treatment of INS resistance in type 2 diabetes, is not effective in improving INS resistance in the advanced stage of cancer cachexia, evidencing that the drug does not have the same beneficial effect in these two diseases.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author