低功率激光照射激活PI3-K/Akt信号通路缓解胰岛素抵抗的分子机制

Insulin resistance is one of the characteristic of metabolic syndrome and type 2 diabetes mellitus, while dysfunction of PI3-K/Akt signaling pathway is closely related to insulin resistance. Low-power laser irradiation (LPLI) can trigger different biological processes through activation of various signaling pathway in cells and widely used in clinical medicine. Recent investigations have shown that LPLI promotes cell proliferation and inhibits cell apoptosis via activating PI3-K/Akt signaling pathway. Nevertheless, the molecular mechanisms involved in the regulation of cell metabolism and amelioration of insulin resistance by activation of PI3-K/Akt signaling pathway in response to LPLI has not yet been elucidated. Using the combination of living-cell fluorescence imaging and traditional cell biology, the current project, for the first time, investigated the molecular mechanisms that LPLI improved glucose and lipid metabolism and ameliorated insulin resistance via activation of PI3-K/Akt signaling pathway in insulin-resistant adipocytes cell model and type 2 diabetes animal model. This study will clarify the downstream signal moleculars which improved glucose and lipid metabolism and the specific signaling pathways which ameliorated insulin resistance upon LPLI treatment. This research will deconstruct the molecular mechanisms of LPLI amelioration of insulin resistance, expand the application of LPLI, provide a new laser therapeutic approach for type 2 diabetes treatment, and further provide new experimental and theoretical evidence for clinical application of LPLI.

胰岛素抵抗是代谢综合症及2型糖尿病的特征之一，而PI3-K/Akt信号功能失调与胰岛素抵抗密切相关。低功率激光照射（LPLI）可以激活多种细胞内信号通路触发不同的生物效应而被广泛应用于临床医学。最近的研究表明LPLI可以激活PI3-K/Akt信号促进细胞增殖并抑制细胞凋亡。然而LPLI激活PI3-K/Akt信号调控细胞代谢及缓解胰岛素抵抗的分子机制尚不清楚。本项目利用活细胞荧光成像与传统细胞生物学相结合的方法首次在胰岛素抵抗的脂肪细胞模型与2型糖尿病动物模型中研究LPLI激活PI3-K/Akt信号改善糖脂代谢从而缓解胰岛素抵抗的作用机制。本课题将阐明LPLI改善糖脂代谢的下游信号分子，揭示LPLI缓解胰岛素抵抗的具体信号通路。本研究将解构LPLI缓解胰岛素抵抗的分子机制，拓展LPLI的应用领域，有望为2型糖尿病的治疗提供一种新的激光治疗方法，并为LPLI的临床应用提供新的实验和理论依据。

低功率激光照射（LPLI）可以激活多种细胞内信号通路触发不同的生物效应而被广泛应用于临床医学。本项目旨在利用活细胞荧光成像与传统细胞生物学相结合的方法在胰岛素抵抗的脂肪细胞模型与2型糖尿病动物模型中研究LPLI改善糖脂代谢从而缓解胰岛素抵抗的分子机制。期望通过阐明LPLI改善糖脂代谢的下游信号分子，解构LPLI缓解胰岛素抵抗的分子机制，拓展LPLI的应用领域，为LPLI的临床应用提供新的实验和理论依据。在本项目的支持下，课题研究进展顺利。研究中，我们发现LPLI处理糖尿病小鼠后，能显著降低血糖和血脂，从而改善胰岛素抵抗。进一步的研究表明LPLI能促进小鼠骨骼肌组织中的糖摄取，增加糖元的积累，降低脂肪的沉积，从而改善糖脂代谢紊乱。机制上的研究发现，LPLI促进了活性氧的瞬时产生，活性氧氧化PTEN使其失活，进而活化了AKT信号通路，AKT信号通路的活化使得逆转糖脂代谢紊乱成为可能。