Alpha-synuclein elicits glucose uptake and utilization in adipocytes through the Gab1/PI3K/Akt transduction pathway
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Cellular and Molecular Life Sciences
RESEARCH ARTICLE
Alpha-synuclein elicits glucose uptake and utilization in adipocytes through the Gab1/PI3K/Akt transduction pathway Gerardo Rodriguez-Araujo • Hironori Nakagami • Hiroki Hayashi • Masaki Mori • Tetsuya Shiuchi • Yasuhiko Minokoshi • Yoshikazu Nakaoka Yoichi Takami • Issei Komuro • Ryuichi Morishita • Yasufumi Kaneda
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Received: 2 July 2012 / Revised: 10 October 2012 / Accepted: 15 October 2012 Ó Springer Basel 2012
Abstract Insulin is the main glucoregulator that promotes the uptake of glucose by tissues and the subsequent utilization of glucose as an energy source. In this paper, we describe a novel glucoregulator, the alpha-synuclein (SNCA) protein, that has previously been linked to Parkinson’s disease. Treatment with recombinant SNCA promotes glucose uptake in vitro in preadipocytes and in vivo in the adipose tissues and skeletal muscles of mice through the LPAR2/Gab1/PI3K/Akt pathway; these effects occur independently of the insulin receptor. This function of SNCA represents a new mechanistic insight that creates novel avenues of research with respect to the process of glucose regulation. Keywords Glucose uptake Glucose utilization Alpha-synuclein Gab1 Adipocytes Myocytes
Electronic supplementary material The online version of this article (doi:10.1007/s00018-012-1198-8) contains supplementary material, which is available to authorized users. G. Rodriguez-Araujo H. Nakagami (&) H. Hayashi M. Mori Y. Takami Y. Kaneda (&) Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan e-mail: [email protected] Y. Kaneda e-mail: [email protected] G. Rodriguez-Araujo e-mail: [email protected] H. Nakagami Division of Vascular Medicine and Epigenetics, United Graduate School of Child Development, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
Introduction Insulin is the primary glucoregulator in mammals; in combination with other hormones, insulin maintains glucose uptake and glycogen synthesis in tissues and regulates the utilization of glucose as an energy source. A better understanding of glucose regulation and the molecules that participate in this process will facilitate better targeting of novel therapeutic candidates that can optimize and/or control glucose utilization in insulin target organs, such as skeletal muscle and adipose tissue. In this study, we identified a novel player that is involved in glucose regulation, alpha-synuclein (SNCA). The SNCA has been well studied because its mutated variants are associated with Parkinson’s disease [1]. Non-mutant SNCA has important functions in the brain, regulating exocytosis through the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex in the presynaptic aspects of neurotransmissions during the process of aging [2] and preventing T. Shiuchi Y. Minokoshi Division of Endocrinology and Metabolism, Department of Developmental Physiology, Nat
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