Insulin Modulation of fMRI Connectivity and Food Reward

 描述（由申请人提供）：胰岛素是胰腺对食物摄入导致的葡萄糖水平升高做出反应而释放的一种激素。除了刺激外周的葡萄糖摄取外，胰岛素还向中枢神经系统发出信号以诱导饱腹感并抑制进食行为。以前的研究比较了肥胖和瘦个体对可口食物的大脑反应，或者通过摄入混合餐。然而，肥胖是一种复杂的代谢状态，混合餐前负荷诱导多种激素的变化。此外，目前还不清楚胰岛素抵抗如何改变循环胰岛素影响大脑活动的能力。目前的研究建立在K 01项目的基础上，该项目比较了胰岛素抵抗和健康个体在空腹和混合餐前负荷后对可口食物的大脑反应。初步研究结果表明，与健康对照组相比，餐后胰岛素抵抗个体的纹状体--一个涉及奖励的网络--表现出高度反应性。为了开始确定这些发现的机制基础，目前的研究将招募健康的参与者，他们将接受两次功能性磁共振成像扫描。一次扫描将在空腹状态下进行，另一次扫描将在等糖基化高胰岛素钳夹期间进行。这个项目将使我们能够确定循环胰岛素对大脑对可口食物反应的具体影响。我们还将使用最先进的功能成像技术来确定胰岛素如何影响大脑区域之间的功能连接，特别是纹状体。该研究小组包括功能和结构神经成像专家霍华德艾森斯坦博士，临床内分泌学家弗雷德里克托莱多博士，在实施和解释钳夹研究方面拥有多年经验，以及神经科学家约翰瑞安博士（PI），专门研究糖尿病对大脑的影响。这项工作将弥合K 01项目的发现，并为未来在胰岛素抵抗个体中的研究奠定基础，以确定大脑中的胰岛素抵抗如何改变外周激素提供适当反馈信号的能力。

 DESCRIPTION (provided by applicant): Insulin is a hormone released by the pancreas in response to increases in glucose levels that result from food intake. In addition to stimulating glucose uptake in the periphery, insulin signals the central nervous system to induce satiety and inhibit feeding behavior. Previous studies have compared brain responses to palatable food receipt across obese and lean individuals, or through the ingestion of a mixed meal. However, obesity is a complex metabolic state, and a mixed meal preload induces changes in a variety of hormones. Furthermore, it is unknown how insulin resistance may alter the ability of circulating insulin to affect brain activity. The current study builds upon a K01 project that is comparing brain responses to palatable food across insulin resistant and healthy individuals, during fasting and after a mixed meal preload. Initial findings show that following a meal, insulin resistant individuals show a hyper-reactivity of the striatum - a network involved in reward - relative to healthy controls. To begin to identify the mechanistic basis of these findings, the current study will recruit healthy participants who will undergo two functional magnetic resonance imaging scans. One scan will be performed in the fasted state, and the alternate scan will be conducted during an isoglycemic hyperinsulinemic clamp. This project will allow us to identify the specific effects of circulating insulin on brain reactivity to palatable food. We will also use state of theart functional imaging techniques to identify how insulin affects the functional connectivity between brain regions, particularly those in the striatum. The study team includes Dr. Howard Aizenstein, an expert in functional and structural neuroimaging, Dr. Frederico Toledo, a clinical endocrinologist with years of experience in implementing and interpreting clamp studies, and Dr. John Ryan (PI), a neuroscientist who specializes in the effects of diabetes on the brain. This work will bridge the findings of the K01 project and lay the groundwork for future studies in insulin resistant individuals to identify how insulin resistance in the brain may alter the abilityof peripheral hormones to provide appropriate feedback signals.