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.
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Authors | Gerardo Rodriguez-Araujo, Hironori Nakagami, Yoichi Takami, Tomohiro Katsuya, Hiroshi Akasaka, Shigeyuki Saitoh, Kazuaki Shimamoto, Ryuichi Morishita, Hiromi Rakugi, Yasufumi Kaneda |
Journal | Scientific reports
(Sci Rep)
Vol. 5
Pg. 12081
(Jul 10 2015)
ISSN: 2045-2322 [Electronic] England |
PMID | 26159928
(Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Dietary Fats
- Insulin
- alpha-Synuclein
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
- Glucose
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Topics |
- Adipose Tissue
(metabolism)
- Animals
- Body Mass Index
- Cross-Sectional Studies
(methods)
- Diet, High-Fat
- Dietary Fats
(metabolism)
- Glucose
(metabolism)
- Humans
- Insulin
(metabolism)
- Insulin Resistance
(physiology)
- Mice
- Mice, Knockout
- Muscle, Skeletal
(metabolism)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Signal Transduction
(physiology)
- alpha-Synuclein
(blood, metabolism)
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