Hoenig M, Thomaseth K, Brandao J, Waldron M, Ferguson D C
Department of Physiology and Pharmacology, University of Georgia College of Veterinary Medicine, Athens, GA, USA.
Domest Anim Endocrinol. 2006 Nov;31(4):373-89. doi: 10.1016/j.domaniend.2005.12.004. Epub 2006 Jan 11.
Insulin sensitivity (SI) of glucose disposal can be quantified with the euglycemic hyperinsulinemic clamp (EHC) with tracer glucose infusion. True steady state is, however, difficult to achieve, and non-steady state analysis of EHC data is preferred. This analysis requires information on glucose kinetics that can be obtained from bolus injection of cold and tracer glucose. The aim of this study was to assess glucose kinetics in cats. Mathematical modeling and non-steady state analysis was applied to assess effects of obesity on glucose turnover, glycolysis/glycogen synthesis, SI, and inhibition of endogenous glucose production (EGP) in lean cats (L) and obese cats (O). D-[3-(3)H]-glucose kinetics and 3H-H2O production were analyzed in 4 L and 4 O with three-compartment modeling. Frequently sampled insulin-modified intravenous glucose tolerance tests (FSIGT) with minimal model analysis were performed in 5L and 3 O to assess glucose kinetics and SI. EHC was performed in 10 L and 10 O with primed-constant infusion of 3H-glucose. Data were analyzed with a modified minimal model segregating suppression of EGP by insulin using a non-linear mixed-effects population approach. FSIGT provided estimates of SI, glucose effectiveness SG, and distribution volume. EHC provided estimates of SI, SG, glycolysis, and suprabasal insulin concentration for 50% EGP inhibition. Obesity appears to affect glucose distribution but not utilization at basal insulin, and reduces SI estimated by FSIGT and EHC. Differences in SI between FSIGT and EHC depend on different descriptions of EGP inhibition by insulin. Finally, glucose disposal at basal insulin appears to occur entirely through glycolysis, whereas significant amounts of glucose are sequestrated from oxidation during EHC.
葡萄糖处置的胰岛素敏感性（SI）可通过示踪葡萄糖输注的正常血糖高胰岛素钳夹技术（EHC）进行量化。然而，真正的稳态很难实现，因此更倾向于对EHC数据进行非稳态分析。这种分析需要有关葡萄糖动力学的信息，而这些信息可通过静脉注射冷葡萄糖和示踪葡萄糖获得。本研究的目的是评估猫的葡萄糖动力学。应用数学建模和非稳态分析来评估肥胖对瘦猫（L）和肥胖猫（O）的葡萄糖周转率、糖酵解/糖原合成、SI以及内源性葡萄糖生成（EGP）抑制的影响。采用三室模型分析了4只瘦猫和4只肥胖猫的D-[3-(3)H]-葡萄糖动力学及3H-H2O生成情况。对5只瘦猫和3只肥胖猫进行了频繁采样的胰岛素改良静脉葡萄糖耐量试验（FSIGT）并采用最小模型分析，以评估葡萄糖动力学和SI。对10只瘦猫和10只肥胖猫进行了EHC，采用3H-葡萄糖的首剂-恒速输注。使用非线性混合效应群体方法，通过改良的最小模型分析数据，将胰岛素对EGP的抑制作用分离出来。FSIGT提供了SI、葡萄糖效能SG和分布容积的估计值。EHC提供了SI、SG、糖酵解以及50%EGP抑制时的基础胰岛素浓度以上的胰岛素浓度的估计值。肥胖似乎会影响基础胰岛素水平下的葡萄糖分布，但不影响其利用，并降低了FSIGT和EHC估计的SI。FSIGT和EHC之间SI的差异取决于胰岛素对EGP抑制的不同描述。最后，基础胰岛素水平下的葡萄糖处置似乎完全通过糖酵解进行，而在EHC期间，大量葡萄糖从氧化过程中被隔离。
