A novel, rapid, inhibitory effect of insulin on α₁β₂γ_2s γ-aminobutyric acid type A receptors

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• 作者：Daniel B. Williams
• 关键词：GABA_A ; Insulin ; Brain ; Diabetes ; Metabolic syndrome
• 刊名：Neuroscience Letters
• 出版年：2008
• 出版时间：26 September 2008
• 年：2008
• 卷：443
• 期：1
• 页码：27-31
• 全文大小：175 K

文摘

In the CNS, GABA and insulin seem to contribute to similar processes, including neuronal survival; learning and reward; and energy balance and food intake. It is likely then that insulin and GABA may interact, perhaps at the GABA_A receptor. One such interaction has already been described [Q. Wan, Z.G. Xiong, H.Y. Man, C.A. Ackerley, J. Braunton, W.Y. Lu, L.E. Becker, J.F. MacDonald, Y.T. Wang, Recruitment of functional GABA(A) receptors to postsynaptic domains by insulin, Nature 388 (1997) 686–690]; in it a micromolar concentration of insulin causes the insertion of GABA_A receptors into the cell membrane, increasing GABA current. I have discovered another effect of insulin on GABA_A currents. Using a receptor isoform, α₁β₂γ_2s that is the likely main neuronal GABA_A isoform expressed recombinantly in Xenopus oocytes, insulin inhibits GABA-induced current when applied simultaneously with low concentrations of GABA. Insulin will significantly inhibit currents induced by EC_30–50 concentrations of GABA by about 38 % . Insulin is potent in this effect; IC₅₀ of insulin was found to be about 4.3 × 10⁻¹⁰ M. The insulin effect on the GABA dose responses looked like that of an antagonist similar to bicuculline or β-carbolines. However, an effect of phosphorylation on the GABA_A receptor from the insulin receptor signal transduction pathway cannot yet be dismissed.