Pharmacological Strategies for Insulin Sensitivity in Obesity and Cancer: Thiazolidinediones and Metformin

Abstract

Background: Chronic diseases, such as obesity and cancer, have high prevalence rates. Both diseases have hyperinsulinemia, hyperglycemia, high levels of IGF-1 and inflammatory cytokines in common. Therefore, these can be considered triggers for cancer development and growth. In addition, low-grade inflammation that modulates the activation of immune cells, cellular metabolism, and production of cytokines and chemokines are common in obesity, cancer, and insulin resistance. Pharmacological strategies are necessary when a change in lifestyle does not improve glycemic homeostasis. In this regard, thiazolidinediones (TZD) possess multiple molecular targets and regulate PPARγ in obesity and cancer related to insulin resistance, while metformin acts through the AMPK pathway.

Objective: The aim of this study was to review TZD and metformin as pharmacological treatments for insulin resistance associated with obesity and cancer.

Conclusion: Thiazolidinediones restored adiponectin secretion and leptin sensitivity, reduced lipid droplets in hepatocytes and orexigen peptides in the hypothalamus. In cancer cells, TZD reduced proliferation, production of reactive oxygen species, and inflammation by acting through the mTOR and NFκB pathways. Metformin has similar effects, though these are AMPK-dependent. In addition, both drugs can be efficient against certain side effects caused by chemotherapy.

Keywords: Insulin resistance; cancer; chemotherapy; metformin; obesity; thiazolidinediones..