Importance of Glucose Per Se to Intravenous Glucose Tolerance: Comparison of the Minimal-Model Prediction with Direct Measurements

• DOI: 10.2337/diab.34.11.1092
• Publication Date: 2013-09-19T17:16:02Z
• Authors: Marilyn Ader; Giovanni Pacini; Yeon J Yang; Richard N Bergman
• Keywords: Tolbutamide; Basal (medicine); Insulin response

Glucose disappearance after an oral or intravenous challenge is a function of the effects both endogenously secreted insulin and glucose itself. We previously introduced term “glucose effectiveness,” SG, defined as ability per se to enhance its own independent increment in plasma insulin. The present investigation, performed conscious dogs, was undertaken quantify this effect by minimal-model-based analysis dynamics frequently sampled tolerance test (FSIGT). values from standard FSIGT were then compared with direct measurementsobtained experiments which dynamic response suppressed somatostatin (SRIF). In addition, we examined SG modified protocol, involves tolbutamide injections. Protocol I (N = 9): FSIGTs data analyzed computer. KG 2.65 ± 0.28 min−1, S1 4.09 0.34 × 10−4 min−1/(μU/ml), 0.033 0.004 min−1. II 6): on animals SRIF infused (0.8 μg/min−1kg) obliterate injection. Before FSIGT, glucagon intraportally reattain basal glycemia. Without insulin, reduced 0.96 0.18 min−1 (P < 0.0001). However, estimated exponential rate fall absence similar FSIGTs: 0.025 > 0.25). III wereperformed using injections for better estimate model parameters. Model parameters KGwere not different 0.3). fact, value (0.028 0.003 min−1) nearly identical measure protocol II. Therefore, decline, modeling FSIGTs, confirmed measurement endogenous SRIF. Also, time course net [leff(t)] calculated II, same coursepredicted model. These studies demonstrate computer approach separate insulin-dependent glucose-dependent disappearance, represent confirmation minimal More important, they confirm that se, response, very significant factor determination tolerance.