Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli", via Costantinopoli 16, 80138 Naples, Italy.
Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli", via Costantinopoli 16, 80138 Naples, Italy.
Pharmacol Ther. 2024 Nov;263:108724. doi: 10.1016/j.pharmthera.2024.108724. Epub 2024 Sep 18.
Diabetes causes macrovascular and microvascular complications such as peripheral neuropathy. Glutamate regulates insulin secretion in pancreatic β-cells, and its increased activity in the central nervous system is associated with peripheral neuropathy in animal models of diabetes. One strategy to modulate glutamatergic activity consists in the pharmacological manipulation of metabotropic glutamate receptors (mGluRs), which, compared to the ionotropic receptors, allow for a fine-tuning of neurotransmission that is compatible with therapeutic interventions. mGluRs are a family of eight G-protein coupled receptors classified into three groups (I-III) based on sequence homology, transduction mechanisms, and pharmacology. Activation of group II and III or inhibition of group I represents a strategy to counteract the glutamatergic hyperactivity associated with diabetic neuropathy. In this review article, we will discuss the role of glutamate receptors in the release of insulin and the development/treatment of diabetic neuropathy, with particular emphasis on their manipulation to prevent the glutamatergic hyperactivity associated with diabetic neuropathy.
糖尿病可引起大血管和微血管并发症，如周围神经病变。谷氨酸调节胰岛β细胞胰岛素的分泌，其在中枢神经系统中的活性增加与糖尿病动物模型中的周围神经病变有关。调节谷氨酸能活性的一种策略是对代谢型谷氨酸受体（mGluRs）进行药理学操作，与离子型受体相比，mGluRs 允许对神经传递进行微调，这与治疗干预是兼容的。mGluRs 是一个由八个 G 蛋白偶联受体组成的家族，根据序列同源性、转导机制和药理学分为三组（I-III）。激活 II 组和 III 组或抑制 I 组是对抗与糖尿病神经病变相关的谷氨酸能过度活跃的一种策略。在这篇综述文章中，我们将讨论谷氨酸受体在胰岛素释放和糖尿病性神经病的发展/治疗中的作用，特别强调了它们在预防与糖尿病性神经病相关的谷氨酸能过度活跃方面的操作。
