Diabetes, Metabolic Syndrome and Obesity (Feb 2023)

The Neuronal and Non-Neuronal Pathways of Sodium-Glucose Cotransporter-2 Inhibitor on Body Weight-Loss and Insulin Resistance

  • Dong M,
  • Chen H,
  • Wen S,
  • Yuan Y,
  • Yang L,
  • Li Y,
  • Yuan X,
  • Xu D,
  • Zhou L

Journal volume & issue
Vol. Volume 16
pp. 425 – 435

Abstract

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Meiyuan Dong,1,2 Huiling Chen,2 Song Wen,2 Yue Yuan,2 Liling Yang,2 Yanyan Li,2 Xinlu Yuan,2 Dongxiang Xu,2 Ligang Zhou1– 3 1Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email [email protected]: With the emergence of sodium-glucose cotransporter 2 inhibitors (SGLT2i), the treatment of type 2 diabetes mellitus (T2DM) has achieved a new milestone, of which the insulin-independent mechanism could produce weight loss, improve insulin resistance (IR) and exert other protective effects. Besides the well-acknowledged biochemical processes, the dysregulated balance between sympathetic and parasympathetic activity may play a significant role in IR and obesity. Weight loss caused by SGLT-2i could be achieved via activating the liver–brain–adipose neural axis in adipocytes. We previously demonstrated that SGLT-2 are widely expressed in central nervous system (CNS) tissues, and SGLT-2i could inhibit central areas associated with autonomic control through unidentified pathways, indicating that the role of the central sympathetic inhibition of SGLT-2i on blood pressure and weight loss. However, the exact pathway of SGLT2i related to these effects and to what extent it depends on the neural system are not fully understood. The evidence of how SGLT-2i interacts with the nervous system is worth exploring. Therefore, in this review, we will illustrate the potential neurological processes by which SGLT2i improves IR in skeletal muscle, liver, adipose tissue, and other insulin-target organs via the CNS and sympathetic nervous system/parasympathetic nervous system (SNS/PNS).Keywords: sodium-glucose cotransporter 2 inhibitors, central nervous system, autonomic nervous system, insulin resistance, weight loss

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