Institute of Nutrition and Functional Foods, Laval University , Quebec City, Quebec , Canada.
Department of Gastroenterology, Centre hospitalier universitaire de Québec-Laval University , Quebec City, Quebec , Canada.
Am J Physiol Gastrointest Liver Physiol. 2018 Aug 1;315(2):G177-G184. doi: 10.1152/ajpgi.00108.2018. Epub 2018 Apr 26.
The mechanisms underlying the oversecretion of apolipoprotein (apo)B-48-containing triglyceride-rich lipoproteins (TRL) in insulin-resistance (IR) states in humans remain to be fully understood. The objective of this study was to evaluate the association between the plasma levels of insulin and glucose and the intestinal expression of key genes involved in chylomicron metabolism in a large sample of nondiabetic men displaying various degrees of IR. Duodenal biopsies were obtained by gastroduodenoscopy in 127 men free of intestinal disease. Gene expression was measured using quantitative PCR in duodenal samples. Plasma insulin and glucose concentrations were measured in the fasting state. Postprandial TRL apoB-48 kinetics were measured using a primed-constant infusion of l-[5,5,5-D]leucine for 12 h in a subgroup of 75 subjects maintained in a constant fed state. Plasma insulin levels were negatively associated with intestinal expression of ACS1 (standard β = -0.20, P = 0.007), DGAT1 (β = -0.18, P = 0.001), DGAT2 (β = -0.20, P = 0.02), and MTP (β = -0.27, P = 0.0005), whereas glucose levels were positively associated with MTP expression (β = 0.15, P = 0.04) independent of age, BMI, waist circumference, dietary intake, and duodenal expression of SREBP1c. Insulin levels, but not glucose concentrations, were positively correlated with postprandial TRL apoB-48 production rate ( r = 0.24, P = 0.04) and pool size ( r = 0.27, P = 0.03). In conclusion, plasma insulin and glucose levels are differentially associated with the expression of key genes involved in chylomicron metabolism. These results suggest that alterations in intestinal lipoprotein metabolism associated with IR may be regulated by plasma levels of both insulin and glucose concurrently and are therefore likely modified by the onset of insulin insufficiency. NEW & NOTEWORTHY We demonstrate that plasma insulin and glucose levels are differentially associated with the expression of key genes involved in chylomicron metabolism in men. For instance, intestinal expression of MTP is negatively associated with plasma insulin concentrations and positively associated with plasma glucose concentrations. Alterations in intestinal lipoprotein metabolism associated with insulin resistance may be regulated by plasma levels of both insulin and glucose concurrently and are therefore likely modified by the onset of insulin insufficiency.
在人类胰岛素抵抗（IR）状态下，载脂蛋白（apo）B-48 含甘油三酯丰富的脂蛋白（TRL）的过度分泌的机制仍有待充分理解。本研究的目的是评估在显示不同程度 IR 的大量非糖尿病男性中，血浆胰岛素和葡萄糖水平与参与乳糜微粒代谢的关键基因在肠道中的表达之间的关联。通过胃镜检查从 127 名无肠道疾病的男性中获得十二指肠活检。使用定量 PCR 在十二指肠样本中测量基因表达。在空腹状态下测量血浆胰岛素和葡萄糖浓度。在 75 名受试者的亚组中，通过使用 l-[5,5,5-D]亮氨酸的引物恒定输注 12 小时来测量餐后 TRL apoB-48 动力学，该亚组保持在恒定的喂养状态。血浆胰岛素水平与 ACS1（标准β= -0.20，P = 0.007）、DGAT1（β= -0.18，P = 0.001）、DGAT2（β= -0.20，P = 0.02）和 MTP（β= -0.27，P = 0.0005）的肠内表达呈负相关，而葡萄糖水平与 MTP 表达呈正相关（β= 0.15，P = 0.04），与年龄、BMI、腰围、饮食摄入和 SREBP1c 在十二指肠中的表达无关。胰岛素水平，而不是葡萄糖浓度，与餐后 TRL apoB-48 产生率（r = 0.24，P = 0.04）和池大小（r = 0.27，P = 0.03）呈正相关。总之，血浆胰岛素和葡萄糖水平与乳糜微粒代谢相关的关键基因的表达存在差异。这些结果表明，与 IR 相关的肠内脂蛋白代谢的改变可能同时受到血浆胰岛素和葡萄糖水平的调节，因此可能会因胰岛素不足的发生而改变。
值得注意的是，我们证明了在男性中，血浆胰岛素和葡萄糖水平与乳糜微粒代谢相关的关键基因的表达存在差异。例如，MTP 的肠内表达与血浆胰岛素浓度呈负相关，与血浆葡萄糖浓度呈正相关。与胰岛素抵抗相关的肠内脂蛋白代谢的改变可能同时受到血浆胰岛素和葡萄糖水平的调节，因此可能会因胰岛素不足的发生而改变。
