title: 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.
authors.affiliation: Division of Gene Therapy Science.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Rodriguez-Araujo
authors.affiliation: Department of Geriatric Medicine.
authors.forename: Hironori
authors.initials: H
authors.lastname: Nakagami
authors.affiliation: Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takami
authors.affiliation: Division of Vascular Medicine and Epigenetics, United Graduate School of Child Development, Osaka University, 2-1 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.affiliation: Sapporo Medical University Hospital, Second Department of Internal Medicine.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akasaka
authors.affiliation: Sapporo Medical University Hospital, Second Department of Internal Medicine.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Saitoh
authors.affiliation: Sapporo Medical University Hospital, Second Department of Internal Medicine.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimamoto
authors.affiliation: Division of Vascular Medicine and Epigenetics, United Graduate School of Child Development, Osaka University, 2-1 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
authors.affiliation: Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.affiliation: Division of Gene Therapy Science.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015992:Body Mass Index; D003430:Cross-Sectional Studies / Q000379:methods; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051844:alpha-Synuclein / Q000097:blood* / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D007328:Insulin; D051844:alpha-Synuclein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose