MECHANISMS OF HUMAN INSULIN RESISTANCE: BARIATRIC SURGERY

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。胰岛素抵抗综合征（IR）为2型糖尿病和心血管疾病的发展提供了“共同土壤”，并导致了我们社会中广泛的发病率和死亡率。减肥手术（BS）为病态肥胖患者提供了持续减肥的有效治疗方法。与外科手术相关的代谢改善包括胰岛素释放、胰岛素抵抗和葡萄糖利用的增强。这些患者胰岛素敏感性改善的机制尚不清楚，可能与热量和大量营养素摄入明显减少以及手术引起的脂肪异常有关。此外，BS模型提供了研究绕过大部分胃和十二指肠对肠-岛轴的影响及其对不同代谢途径以及饱腹感调节机制的后续影响的机会。因此，我们希望扩大受试者的纳入标准，在我们目前的补助金，肥胖受试者谁达到减肥通过BS。根据我们目前的假设，本研究的总体目标是确定BS对胰岛素敏感性、肠-岛轴和肌内脂肪的影响。将招募接受BS的受试者参与研究。该研究将分为3个阶段-第一阶段：术前1-4周;第二阶段：术后3-6个月;第三阶段：术后12-18个月。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Insulin Resistance Syndrome (IR) provides the "common soil" for the development of type 2 diabetes and cardiovascular disease and is responsible for extensive morbidity and mortality in our society. Bariatric surgery (BS) offers an efficacious treatment for sustained weight loss for morbidly obese patients. The metabolic improvements associated with the surgical procedure include enhancement of insulin release, insulin resistance, and glucose utilization. The mechanisms underlying the improvement in insulin sensitivity in these patients are not understood, and may be related to the marked reduced caloric and macronutrient intake, as well as to the fat malabsportion induced by the procedure. Additionally, the BS model provides the opportunity to study the effect of bypassing most of the stomach and duodenum on the entero-insular axis, and its subsequent effects on different metabolic pathways as well as satiety regulatory mechanisms. Therefore, we want to expand the subjects' inclusion criteria in our current grant, to obese subjects who attain weight loss through BS. In accordance to our current hypotheses, the overall goal of this study will be to determine the effect of BS on insulin sensitivity, the entero-insular axis, and intramyocellular fat. Subjects receiving BS will be recruited for the study. The study will have 3-phases- Phase I: 1-4 wks before surgery; Phase II: 3-6 months after surgery; and Phase III: 12-18 months after surgery.