Pharmacokinetic analysis of intraarticular injection of insulin and its effect on IGF-1 expression in synovial fluid of healthy horses

Abstract

Insulin induces mitosis on equine chondrocytes in vitro and enhances production of type II collagen. Insulin, when administered intra-articularly, changes the composition of synovial fluid, including the concentrations of glucose, insulin and glycemia levels. The concentration of insulin in the joint was measured by using high-performance liquid chromatography (HPLC), which provided pharmacokinetic values. Six mixed breed horses were administered three different doses of insulin into one antebrachiocarpal joint (10, 15 and 20 IU) and isotonic saline was administered into the contralateral joint. The blood glucose concentration significantly changed through time for all three doses (P<0.0001). No significant differences in protein concentration and cell count in synovial fluid were found between treated and control joints (P>0.05), no significant difference in synovial glucose concentrations was found between treated and control joints (P>0.05). Values obtained by HPLC analyzed with PkAnalyst program revealed that the pharmacokinetic values were dose dependent, there was no significant difference in concentration of blood glucose between the three different doses (P>0.05). ELISA for IGF-1 (insulin-like growth factor 1) revealed a significant difference between treated and control joints (P<0.001). Insulin used in this study proved to be innocuous to the equine joint, no more than 20 IU for a 350-400 kg horse should be administered.