Vettor R, Lombardi A M, Fabris R, Pagano C, Cusin I, Rohner-Jeanrenaud F, Federspil G, Jeanrenaud B
Endocrine-Metabolic Laboratory, University of Padova, Italy.
Metabolism. 1997 Jun;46(6):684-90. doi: 10.1016/s0026-0495(97)90014-7.
Plasma lactate is elevated in many physiological and pathological conditions, such as physical exercise, obesity, and diabetes, in which a reduction of insulin sensitivity is also present. Furthermore, an increased production of lactate from muscle and adipose tissue together with increased gluconeogenic substrate flux to the liver plays a primary role in enhancing hepatic glucose production (HGP) in diabetes. It has been shown that lactate may interfere with the utilization and oxidation of other substrates such as free fatty acids (FFAs). The aim of this study was to investigate if lactate infusion affects peripheral glucose utilization in rats. Animals were acutely infused with lactate to achieve a final lactate concentration of 4 mmol/L. They were then submitted to a euglycemic-hyperinsulinemic clamp to study HGP and overall glucose metabolism (rate of disappearance [Rd]). At the end of the clamp, a bolus of 2-deoxy-[1-3H]-glucose was injected to study insulin-dependent glucose uptake in different tissues. The results show that lactate infusion did not affect HGP either in the basal state or at the end of clamp, whereas glucose utilization significantly decreased in lactate-infused rats (26.6 +/- 1.1 v 19.5 +/- 1.4 mg.kg-1.min-1, P < .01). A reduction in the tissue glucose utilization index was noted in heart (18.01 +/- 4.44 v 46.21 +/- 6.51 ng.mg-1.min-1, P < .01), diaphragm (5.56 +/- 0.74 v 9.01 +/- 0.93 ng.mg-1.min-1, P < .01), soleus (13.62 +/- 2.29 v 34.05 +/- 6.08 ng.mg-1.min-1, P < .01), and red quadricep (4.43 +/- 0.73 v 5.88 +/- 0.32 ng.mg-1.min-1, P < .05) muscle in lactate-infused animals, whereas no alterations were observed in other muscles or in adipose tissue. Therefore, we suggest that acute lactate infusion induces insulin resistance in the heart and some muscles, thus supporting a role for lactate in the regulation of peripheral glucose metabolism.
在许多生理和病理状况下，如体育锻炼、肥胖症和糖尿病，血浆乳酸水平会升高，这些情况下胰岛素敏感性也会降低。此外，肌肉和脂肪组织中乳酸生成增加，以及肝脏中糖异生底物通量增加，在糖尿病患者肝脏葡萄糖生成（HGP）增强过程中起主要作用。研究表明，乳酸可能会干扰其他底物（如游离脂肪酸（FFA））的利用和氧化。本研究的目的是调查输注乳酸是否会影响大鼠外周葡萄糖的利用。给动物急性输注乳酸，使最终乳酸浓度达到4 mmol/L。然后对它们进行正常血糖-高胰岛素钳夹试验，以研究肝脏葡萄糖生成和整体葡萄糖代谢（消失率[Rd]）。在钳夹试验结束时，注射一剂2-脱氧-[1-³H]-葡萄糖，以研究不同组织中胰岛素依赖的葡萄糖摄取。结果显示，输注乳酸无论是在基础状态还是钳夹试验结束时，均不影响肝脏葡萄糖生成，而输注乳酸的大鼠葡萄糖利用率显著降低（26.6±1.1对19.5±1.4 mg·kg⁻¹·min⁻¹，P<.01）。在输注乳酸的动物中，心脏（18.01±4.44对46.21±6.51 ng·mg⁻¹·min⁻¹，P<.01）、膈肌（5.56±0.74对9.01±0.93 ng·mg⁻¹·min⁻¹，P<.01）、比目鱼肌（13.62±2.29对34.05±6.08 ng·mg⁻¹·min⁻¹，P<.01）和红色股四头肌（4.43±0.73对5.88±0.32 ng·mg⁻¹·min⁻¹，P<.05）的组织葡萄糖利用指数降低，而在其他肌肉或脂肪组织中未观察到变化。因此，我们认为急性输注乳酸会诱导心脏和某些肌肉产生胰岛素抵抗，从而支持乳酸在调节外周葡萄糖代谢中的作用。
