Central Nervous System Control of Glucose Homeostasis: A Therapeutic Target for Type 2 Diabetes?

IF 11.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Annual review of pharmacology and toxicology Pub Date : 2022-01-06 DOI:10.1146/annurev-pharmtox-052220-010446
Zaman Mirzadeh, Chelsea L Faber, Michael W Schwartz
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Abstract

Historically, pancreatic islet beta cells have been viewed as principal regulators of glycemia, with type 2 diabetes (T2D) resulting when insulin secretion fails to compensate for peripheral tissue insulin resistance. However, glycemia is also regulated by insulin-independent mechanisms that are dysregulated in T2D. Based on evidence supporting its role both in adaptive coupling of insulin secretion to changes in insulin sensitivity and in the regulation of insulin-independent glucose disposal, the central nervous system (CNS) has emerged as a fundamental player in glucose homeostasis. Here, we review and expand upon an integrative model wherein the CNS, together with the islet, establishes and maintains the defended level of glycemia. We discuss the implications of this model for understanding both normal glucose homeostasis and T2D pathogenesis and highlight centrally targeted therapeutic approaches with the potential to restore normoglycemia to patients with T2D.

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中枢神经系统对葡萄糖稳态的控制:2 型糖尿病的治疗目标?
一直以来,胰岛β细胞被视为血糖的主要调节器,当胰岛素分泌不能补偿外周组织的胰岛素抵抗时,就会导致 2 型糖尿病(T2D)。然而,血糖也受胰岛素依赖性机制的调节,而这些机制在 T2D 中失调。有证据表明,中枢神经系统(CNS)在胰岛素分泌与胰岛素敏感性变化的适应性耦合以及胰岛素依赖性葡萄糖处置的调控中都扮演着重要角色。中枢神经系统与胰岛一起建立并维持血糖的防御水平。我们讨论了这一模型对理解正常血糖稳态和 T2D 发病机制的意义,并强调了有可能使 T2D 患者恢复正常血糖的中枢靶向治疗方法。
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来源期刊
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27.80
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0.00%
发文量
53
期刊介绍: Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.
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