Pituitary pars intermedia dysfunction does not necessarily impair insulin sensitivity in old horses

Equine pituitary pars intermedia dysfunction (PPID) has been associated with reduced insulin sensitivity in comparison with younger adult horses; however, the difference in insulin sensitivity between horses with PPID and aged-matched controls has not been well characterized. The objective of the study was to determine if aged horses with PPID had reduced insulin sensitivity and alterations in the insulin-mediated signaling pathways in the skeletal muscle when compared with healthy aged horses. Isoglycemic hyperinsulinemic clamp procedures were conducted in 12 horses that were classified as either PPID (n = 6; age: 25.0 ± 2.5yr; mean ± standard deviation) or non-PPID, aged-matched controls (control) (n = 6; age: 25.7 ± 2.0yr). Blood samples were taken before and during the clamp procedures to measure plasma glucose, insulin, and amino acid concentrations, and 2 muscle biopsies were collected from the gluteus medius muscle, one in the basal state and the second at the end of the clamp procedure (insulin-stimulated state). Plasma insulin concentrations increased ~9-fold during the clamp compared with basal conditions (P < 0.001) in both groups. During the last 30min of the clamp, the rate of glucose infusion required to maintain isoglycemia in horses with PPID was similar to that in the control horses (P = 0.67). The plasma concentrations of most indispensible amino acids were lower in the insulin-stimulated state than the basal state (P < 0.05). PPID status did not have an effect on the activation of factors associated with protein synthesis and breakdown; however, factors associated with protein synthesis had increased phosphorylation in the insulin-stimulated state, compared with basal. The results from this study provide evidence that PPID is not always associated with impairments in insulin sensitivity.