Namdaran K, Bracy D P, Lacy D B, Johnson J L, Bupp J L, Wasserman D H
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
J Appl Physiol (1985). 1997 Oct;83(4):1339-47. doi: 10.1152/jappl.1997.83.4.1339.
Excessive circulating fat levels are a defining feature of poor metabolic control in diabetes. Splanchnic adipose tissue is a source of free fatty acids (FFA), and the liver is a key site of FFA utilization and the sole source of ketones. Despite the role of splanchnic tissues in fat metabolism, little is known about how these tissues respond to diabetes under divergent metabolic conditions. Therefore, splanchnic fat metabolism was studied in poorly controlled diabetes under two conditions. First, it was studied during exercise, a stimulus that enhances FFA flux. Second, it was studied while insulin was being acutely infused to achieve levels normally present during exercise, a treatment that may be expected to inhibit lipolysis. For this purpose, liver and gut arteriovenous differences were used during rest and 2.5 h of treadmill exercise in insulin-deficient (n = 6) and acutely insulin-infused (n = 4) depancreatized (PX) dogs. The data show that 1) exercise, in insulin-deficient PX dogs, leads to an increase in net FFA release from mesenteric fat that is equal in magnitude to the response in nondiabetic dogs; 2) net hepatic fractional FFA extraction is increased twofold during exercise in both insulin-deficient PX dogs and nondiabetic control dogs; 3) during exercise, approximately 40 and 75% of the FFA consumed by the liver is effectively transferred from fat stores mobilized from splanchnic adipose tissue in insulin-deficient PX and nondiabetic dogs, respectively; 4) hepatic ketogenic efficiency is elevated during rest three- to fourfold in insulin-deficient PX dogs compared with nondiabetic control dogs and remains elevated during exercise; and 5) surprisingly, acute insulin replacement is ineffective in normalizing net gut, hepatic, or splanchnic FFA or ketone body balances in PX dogs.
循环脂肪水平过高是糖尿病患者代谢控制不佳的一个显著特征。内脏脂肪组织是游离脂肪酸（FFA）的来源，而肝脏是FFA利用的关键部位以及酮体的唯一来源。尽管内脏组织在脂肪代谢中发挥作用，但对于这些组织在不同代谢条件下如何应对糖尿病却知之甚少。因此，在两种情况下研究了控制不佳的糖尿病患者的内脏脂肪代谢。首先，在运动期间进行研究，运动是一种增强FFA通量的刺激因素。其次，在急性输注胰岛素以达到运动期间正常水平时进行研究，这种治疗预期可抑制脂肪分解。为此，在胰岛素缺乏（n = 6）和急性输注胰岛素（n = 4）的胰腺切除（PX）犬休息时以及跑步机运动2.5小时期间，测量了肝脏和肠道的动静脉差异。数据显示：1）在胰岛素缺乏的PX犬中，运动导致肠系膜脂肪净FFA释放增加，其幅度与非糖尿病犬的反应相当；2）在胰岛素缺乏的PX犬和非糖尿病对照犬中，运动期间肝脏FFA净提取率均增加两倍；3）运动期间，胰岛素缺乏的PX犬和非糖尿病犬肝脏消耗的FFA中，分别约有40%和75%有效地从内脏脂肪组织动员的脂肪储存中转移而来；4）与非糖尿病对照犬相比，胰岛素缺乏的PX犬在休息时肝脏生酮效率提高三到四倍，运动期间仍保持升高；5）令人惊讶的是，急性胰岛素替代对使PX犬的肠道、肝脏或内脏FFA或酮体净平衡正常化无效。
