Pharmacodynamic Effects of Pioglitazone on High Molecular Weight Adiponectin Concentrations and Insulin Response After Oral Sugar in Equids

Abstract

Chronic insulin dysregulation is challenging to manage with pharmaceuticals in horses. Pioglitazone improves insulin sensitivity in humans, and the pharmacokinetics of pioglitazone have been evaluated in horses. The objectives of this study were to assess the pharmacodynamic effects of oral pioglitazone on morphometric parameters, hepatic enzyme activity and function, adipokines, and enteroinsular response to oral sugar. A prospective pilot study was performed using fifteen adult equids (8 ponies, 7 horses) to evaluate the effects of short-term pioglitazone administration (2 mg/kg PO q 24 hours, 28 days). Oral sugar tests (OST) were performed before and after treatment. Adipokines were measured at day 0, 14, and 28 of administration. Plasma drug concentrations were measured at day 14 and 28 of administration. The subjects were grouped into horses, ponies, and insulin dysregulated (ID) animals. Baseline values for all parameters were compared with values obtained at day 14 and 28 using one-way or two-way analysis of variance. Mild changes were noted in morphometric parameters and hepatic enzymes. No differences were found in leptin concentrations or the blood glucose response to the OST. Significant decreases were found in the insulin response to OST at 90 and 120 minutes time points and the area under the curve after pioglitazone treatment in the pony and ID groups. High-molecular-weight (HMW) adiponectin concentrations were significantly increased in all groups after pioglitazone treatment. Decreased insulin concentrations in response to oral sugar and increased HMW adiponectin concentrations indicate positive effects of pioglitazone for treatment of metabolic derangements in equine metabolic syndrome, which warrant future clinical study.

Keywords: EMS; Endocrinopathic laminitis; Insulin dysregulation; Pioglitazone.