Original ResearchCharacterization of Glucose Response Curves after Insulin Injection in Sensitive versus Insensitive Mares
Introduction
Caltabilota et al. [1] reported that the percentage of decrease in serum glucose concentrations in mares after injection of recombinant human insulin could be used to determine insulin sensitivity, with the limitation that multiple data points, preferably three, be obtained between decreases of 10% and 70%, at which point the dose-response curve is linear. Subsequently, Bertin and Sojka-Kritchevsky [2] reported a two-step method based on a single dose of insulin, which compared favorably with the protocol of Caltabilota et al. [1].
In the development of the original technique, Caltabilota et al. [1] noticed that mares with low insulin sensitivities seemed to have less steep dose-response curves. That is, the incremental percentage of decrease in glucose concentrations with each higher dose of insulin in insulin-insensitive mares was not as much as that for insulin-sensitive mares. Caltabilota et al. [1] suggested that three doses of insulin produced the most reliable estimates of insulin sensitivity, even though the response to a single dose of 50 mU per kg of body weight (mU/kg BW) did in fact provide a close approximation to the final sensitivity estimate in most insulin-sensitive mares but less so in mares later diagnosed with insensitivity.
The present experiment was conducted to better characterize the insulin-glucose dose-response curves in mares (a minimum of 5 points) so that differences among horses of differing sensitivities could be assessed. Data from these curves were subsequently used to estimate the predictability of single-injection results compared to those obtained with the multipoint curves.
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Materials and Methods
All procedures described herein were approved by the Institutional Animal Care and Use Committee of the Louisiana State University Agricultural Center. Twelve mares, six known to be insulin insensitive and six known to be insulin sensitive (determined multiple times over several years), were used in this experiment. The mares were between 6 and 16 years of age, weighed between 450 and 650 kg, and had body condition scores of 6 or greater [3]. They were routinely housed on native grass pasture
Results
The pooled regression lines of the log natural doses of insulin plotted versus the percentage decrease in glucose concentrations for the individual mares in the sensitive and insensitive groups in this experiment are shown in Figure 1. Analysis of those regression data revealed that mares considered insulin insensitive in previous trials had a higher y intercept (−35.45% vs. −52.6%; P = .066) (Fig. 2). These insensitive mares also displayed a less steep slope (15.4% vs. 26.2% increase per ln
Discussion
Caltabilota et al. [1] were the first to formalize the use of insulin injection to directly estimate insulin sensitivity in horses. Bertin and Sojka-Kritchevsky [2] subsequently modified their protocol into a two-step method for on-farm use. The previous applications of the hyperinsulinemic-euglycemic clamp [5], [6] and the minimal modeling of the frequently sampled intravenous glucose tolerance test [7], [8] were considered the currently acceptable methods for estimating insulin sensitivity in
Acknowledgments
This report was approved for publication by the director of the Louisiana Agricultural Experiment Station as manuscript number 2012-230-7781.
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