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Low alpha-synuclein levels in the blood are associated with insulin resistance.

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.
AuthorsGerardo Rodriguez-Araujo, Hironori Nakagami, Yoichi Takami, Tomohiro Katsuya, Hiroshi Akasaka, Shigeyuki Saitoh, Kazuaki Shimamoto, Ryuichi Morishita, Hiromi Rakugi, Yasufumi Kaneda
JournalScientific reports (Sci Rep) Vol. 5 Pg. 12081 (Jul 10 2015) ISSN: 2045-2322 [Electronic] England
PMID26159928 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
Chemical References
  • Dietary Fats
  • Insulin
  • alpha-Synuclein
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Glucose
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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