Expression Profile-Dependent Improvement of Insulin Sensitivity by Gene Delivery of Interleukin-6 in a Mouse Model of Type II Diabetes

Abstract

Type II diabetes is one of the most problematic metabolic disorders and is associated with secondary conditions such as heart disease and eye complications. Interleukin-6 (IL-6), a multifunctional cytokine, could influence conditions of altered glucose metabolism such as insulin resistance in diabetic patients. However, a consensus about the role of IL-6 on glucose metabolism has not been reached. The aim of the present study is to investigate whether the expression of IL-6 affects glucose metabolism in diet-induced obesity (DIO) mice, a model of type II diabetes and obesity, using gene delivery of IL-6. DIO mice received hydrodynamic or intramuscular injection of IL-6-expressing plasmid to investigate the importance of the site of IL-6 expression. DIO mice that received a sustained IL-6 gene transfer showed similar glucose levels to lean mice in a glucose tolerance test. DIO mice exhibited reduced food intake and low body and epididymal fat weights after IL-6 gene transfer. IL-6 gene delivery reduced the mRNA expression of metabolism-related genes in the liver, skeletal muscle, and adipose tissue of DIO mice. The metabolic status of DIO mice receiving intramuscular injections was moderately better than that of DIO mice receiving hydrodynamic injections. The infiltration of inflammatory cells into the sites where the IL-6-expressing plasmid DNA was delivered was observed. Transient expression of IL-6 had limited effects on all parameters examined. These results indicate that the expression of IL-6 has an effect on obesity and the metabolism of glucose and lipid in diabetic mice and that the expression site of IL-6 is not an important factor.