Measurement of C-peptide concentrations and responses to somatostatin, glucose infusion, and insulin resistance in horses

Reasons for performing study: Hyperinsulinaemia is detected in horses with insulin resistance (IR) and has previously been attributed to increased pancreatic insulin secretion. Connecting peptide (C-peptide) can be measured to assess pancreatic function because it is secreted in equimolar amounts with insulin and does not undergo hepatic clearance. Hypothesis: A human double antibody radioimmunoassay (RIA) detects C-peptide in equine serum and concentrations would reflect responses to different stimuli and conditions. Methods: A validation procedure was performed to assess the RIA. Six mature mares were selected and somatostatin administered i.v. as a primed continuous rate infusion, followed by 50 nmol human C-peptide i.v. Insulin and C-peptide concentrations were measured in horses (n = 6) undergoing an insulin-modified frequently sampled i.v. glucose tolerance test, and in horses with insulin resistance (n = 10) or normal insulin sensitivity (n = 20). Results: A human RIA was validated for use with equine sera. Endogenous C-peptide secretion was suppressed by somatostatin and median (range) clearance rate was 0.83 (0.15-1.61) ml/min/kg bwt. Mean ± s.d. C-peptide-to-insulin ratio significantly (P = 0.004) decreased during the glucose tolerance test from 3.60 ± 1.95 prior to infusion to 1.03 ± 0.18 during the first 20 min following dextrose administration. Median C-peptide and insulin concentrations were 1.5- and 9.5-fold higher, respectively in horses with IR, compared with healthy horses. Conclusions: Endogenous C-peptide secretion decreases in response to somatostatin and increases after dextrose infusion. Results suggest that relative insulin clearance decreases as pancreatic secretion increases in response to dextrose infusion. Hyperinsulinaemia in insulin resistant horses may be associated with both increased insulin secretion and decreased insulin clearance. Potential relevance: Both C-peptide and insulin concentrations should be measured to assess pancreatic secretion and insulin clearance in horses.