近紅外發光二極體光生物調節應用於糖尿病二型血糖調控

Abstract

第二型糖尿病(type 2 diabetes mellitus; T2DM)為全球盛行率持續攀升之代謝性疾病，其核心病理機制與胰島素阻抗、粒線體功能失衡及慢性高血糖密切相關。現行治療方式多仰賴口服降血糖藥物或胰島素注射，然仍伴隨副作用、低血糖風險、長期依賴性等限制。故發展安全、非侵入性且具臨床應用潛力之新穎治療策略，已成為糖尿病研究之重要方向。本研究提出以近紅外光發光二極體(near-infrared light-emitting diode; NIR LED)進行光生物調節(photobiomodulation; PBM)，探討其於第二型糖尿病血糖調控之應用潛力。 本研究首先以細胞色素c氧化酶(cytochrome c oxidase; CCO)吸收峰作為波長設計依據，建構770、810與940 nm三種近紅外光LED系統。於細胞實驗中，藉慢性胰島素暴露建立C2C12肌管細胞胰島素阻抗模型，結果揭示近紅外光照射可提升葡萄糖攝取能力、增加粒線體膜電位、提升CCO酵素活性、增加ATP與NO 含量，並降低ROS與超氧化物累積，同時促進PI3K/Akt訊號傳遞。其中，以770 nm波長於改善胰島素阻抗相關指標之整體效果最為顯著。 於動物實驗中，本研究以db/db小鼠建立第二型糖尿病模型，並以770 nm近紅外光每日照射一週。結果顯示，照光後糖尿病小鼠之葡萄糖耐受性試驗與胰島素耐受性試驗明顯改善，且血清游離脂肪酸、三酸甘油酯與胰島素阻抗指數呈下降趨勢，顯示其可改善胰島素阻抗與脂質代謝異常。此外，於人體試驗中，受試者接受770 nm背部照射後進行口服葡萄糖耐受性試驗，結果揭示近紅外光處理可降低血糖峰值、曲線下面積及改善相對血糖變化，證實其於人體血糖調控亦具正向效益。 綜合上述結果，本研究證實近紅外光光生物調節可於細胞、動物及人體層級促進葡萄糖代謝並改善血糖恆定，其中770 nm為最具潛力之作用波長。此技術具非侵入性、安全性高、可重複使用等優勢，未來有望發展為第二型糖尿病之輔助治療策略與居家健康照護裝置。

Type 2 diabetes mellitus (T2DM) is a metabolic disorder with rapidly increasing global prevalence and is closely linked to insulin resistance, mitochondrial dysfunction, and chronic hyperglycemia. Current treatments mainly rely on oral hypoglycemic agents or insulin injections, but these approaches are limited by side effects, hypoglycemia risk, and long-term dependence. Therefore, safe and non-invasive therapeutic strategies are needed. In this study, near-infrared light-emitting diode (NIR LED)-based photobiomodulation (PBM) was investigated for glycemic regulation in T2DM. Three NIR LED systems (770, 810, and 940 nm) were designed according to the absorption peaks of cytochrome c oxidase. In insulin-resistant C2C12 myotubes, NIR irradiation enhanced glucose uptake, increased mitochondrial membrane potential, elevated CCO activity, promoted ATP and nitric oxide production, reduced reactive oxygen species accumulation, and activated PI3K/Akt signaling. Among the tested wavelengths, 770 nm showed the best overall performance. In db/db diabetic mice, daily treatment with 770 nm NIR light for one week significantly improved glucose tolerance test and insulin tolerance test results, while serum free fatty acid, triglyceride, and HOMA-IR values showed decreasing trends. In human studies, subjects receiving 770 nm back irradiation before an oral glucose tolerance test exhibited reduced peak glucose levels, lower area under the curve, and improved relative glucose responses. In conclusion, NIR photobiomodulation effectively enhanced glucose metabolism and improved glycemic homeostasis at the cellular, animal, and human levels, with 770 nm identified as the most promising wavelength. Due to its non-invasive nature, safety, and reusability, this technology shows strong potential as an adjunct therapy and home healthcare device for the management of T2DM.