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- Title
Low alpha-synuclein levels in the blood are associated with insulin resistance.
- Authors
Rodriguez-Araujo, Gerardo; Kaneda, Yasufumi; Nakagami, Hironori; Takami, Yoichi; Rakugi, Hiromi; Katsuya, Tomohiro; Morishita, Ryuichi; Akasaka, Hiroshi; Saitoh, Shigeyuki; Shimamoto, Kazuaki
- Abstract
Mutations in the protein alpha-synuclein (SNCA) have been linked to Parkinson's disease. We recently reported that non-mutated SNCA enhanced glucose uptake through the Gab1-PI3 kinase-Akt pathway and elucidated its effects on glucose regulation. Here, we examined the association of SNCA with insulin resistance (IR), a condition that is characterized by decreased tissue glucose uptake. Our observations include those from a population study as well as a SNCA-deficient mouse model, which had not previously been characterized in an IR scenario. In 1,152 patients, we found that serum SNCA levels were inversely correlated with IR indicators-body mass index, homeostatic model assessment for IR (HOMA-IR) and immunoreactive insulin (IRI)-and, to a lesser extent, with blood pressure and age. Additionally, SNCA-deficient mice displayed alterations in glucose and insulin responses during diet-induced IR. Moreover, during euglycemic clamp assessments, SNCA knock-out mice fed a high-fat diet (HFD) showed severe IR in adipose tissues and skeletal muscle. These findings provide new insights into IR and diabetes and point to SNCA as a potential candidate for further research.
- Subjects
SERUM; MICE; GLUCOSE metabolism; MULTIVARIATE analysis; BLOOD pressure
- Publication
Scientific Reports, 2015, p12081
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep12081