| Summary: | 碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系 === 101 === Type 2 diabetes mellitus (T2DM) is a common endocrine disease with unknown etiology. Mitochondrial dysfunction has been suggested to participate in the pathogenesis of T2DM. Among the mitochondria-related studies, effects of PTEN-induced kinase 1 (PINK1) on the mitochondrial function is extensively studied. PINK1 is a mitochondrial serine/threonine-protein kinase with the function of protecting cells from stress-induced mitochondrial dysfunction. Several studies indicate that PINK1 expression level is correlated with circulatory concentration of blood sugar and free fatty acids. Knockdown of PINK1 decreases the glucose uptake and expression of fatty acid-binding protein in vitro. Accordingly, we hypothesize that PINK1 may participate in glucose and lipid metabolism, enhance insulin action and therefore decrease insulin resistance and T2DM onset. To further elucidate the roles of PINK1 in diabetic pathogenesis, the present study aimed at addressing the putative involvement of PINK1 in 3T3-L1 adipocytes by examining PINK1 protein expression levels during adipocyte differentiation (adipogenesis). Our results indicated that full length PINK1 was processed to proteins fragments with smaller molecular weights during adipogenesis, while inhibition of adipogenesis abolished this proteolysis processing. We also found that full-length PINK1 interact with parkin to promote mitophagy. In addition, results from fluorescent microscopy showed that filamentous mitochondria turned into punctuated morphology during the adipogenic process. Furthermore, mitochondria DNA copy number and mitochondria membrane potential were decreased in adipogenesis. However, when we used mitochondria division inhibitor, Mdivi-1, we found that it could inhibit adipogenesis and PINK1 processing. The above results suggest that PINK1 might play an important role in adipogenesis through regulating mitochondrial morphology and function, and thus involved in the type 2 diabetic pathogenesis.
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