Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Biomed Pharmacother. 2021 Jun;138:111440. doi: 10.1016/j.biopha.2021.111440. Epub 2021 Mar 2.
The role of gamma-aminobutyric acid (GABA) in attenuates insulin resistance (IR) in type 2 diabetic (T2D) patients and the reduction of the risk of IR in their offspring, and the function of GLUT4, IRS1 and Akt2 genes expression were investigated. T2D was induced by high fat diet and 35 mg/kg of streptozotocin. The male and female diabetic rats were then divided into three groups: CD, GABA, and insulin. NDC group received a normal diet. All the animals were studied for a six-month. Their offspring were just fed with normal diet for four months. Blood glucose was measured weekly in patients and their offspring. Intraperitoneal glucose tolerance test (IPGTT), urine volume, and water consumption in both patients and their offspring were performed monthly. The hyperinsulinemic euglycemic clamp in both patients and their offspring was done and blood sample collected to measure Hemoglobin A1c (HbA1c). IRS1, Akt and GLUT4 gene expressions in muscle were evaluated in all the groups. GABA or insulin therapy decreased blood glucose, IPGTT, and HbA1c in patients and their offspring compared to DC group. They also increased GIR in patients and their offspring. IRS1, Akt and GLUT4 gene expressions improved in both patients in comparison with DC group. GABA exerts beneficial effects on IRS1 and Akt gene expressions in GABA treated offspring. GABA therapy improved insulin resistance in diabetic patients by increasing the expression of GLUT4. It is also indirectly able to reduce insulin resistance in their offspring possibly through the increased gene expressions of IRS1 and Akt.
γ-氨基丁酸（GABA）在减轻 2 型糖尿病（T2D）患者胰岛素抵抗（IR）和降低其后代发生 IR 的风险中的作用，以及 GLUT4、IRS1 和 Akt2 基因表达的功能进行了研究。T2D 由高脂肪饮食和 35mg/kg 链脲佐菌素诱导。然后将雄性和雌性糖尿病大鼠分为三组：CD、GABA 和胰岛素。NDC 组给予正常饮食。所有动物均进行为期 6 个月的研究。他们的后代仅用正常饮食喂养 4 个月。每周测量患者及其后代的血糖。每月对患者及其后代进行腹腔内葡萄糖耐量试验（IPGTT）、尿量和饮水量。对患者及其后代进行高胰岛素正葡萄糖钳夹，并采集血液样本测量糖化血红蛋白（HbA1c）。评估所有组的肌肉中 IRS1、Akt 和 GLUT4 基因表达。与 DC 组相比，GABA 或胰岛素治疗可降低患者及其后代的血糖、IPGTT 和 HbA1c。它们还增加了患者及其后代的 GIR。与 DC 组相比，患者 IRS1 和 Akt 基因表达均有所改善。与未接受 GABA 治疗的后代相比，GABA 治疗可改善 IRS1 和 Akt 基因表达，从而改善胰岛素抵抗。GABA 治疗通过增加 GLUT4 的表达来改善糖尿病患者的胰岛素抵抗。它还可以通过增加 IRS1 和 Akt 的基因表达间接降低其后代的胰岛素抵抗。
