Department of Endocrinology, Shanghai 10th People Hospital, Tongji University School of Medicine, Shanghai, China.
J Cell Mol Med. 2020 Jun;24(12):6773-6780. doi: 10.1111/jcmm.15328. Epub 2020 May 12.
It was reported that either orexigenic neuropeptide galanin or anorexigenic hormone leptin caught benefit insulin sensitivity through increasing the translocation of glucose transporter 4 (GLUT4) in patients with diabetes. To date, it is unknown whether galanin can potentiate the effect of leptin on alleviation of insulin resistance. Therefore, in the current study we sought to assess the combined effect of central leptin and galanin on insulin resistance in the adipose tissues of type 2 diabetic rats. Galanin and leptin were injected into the intracerebroventricle of the diabetic rats, respectively, or cooperatively once a day for 2 weeks. Then, several indexes of insulin resistance were examined. The results showed that glucose infusion rates in the hyperinsulinaemic-euglycaemic clamp test, plasma adiponectin content and GLUT4 translocation, as well as Akt phosphorylation in fat cells, were higher, not GLUT4 protein and GLUT4 mRNA expression, but HOMA index was lower in the galanin + leptin group than either one of them. Furthermore, treatment with MK-2206, an Akt inhibitor, blocked the combined effects of galanin + leptin on alleviation of insulin resistance. These results suggest that galanin can improve the leptin-induced mitigative effects on insulin resistance in the fat cells, and those provided new insights into the potential tactics for prevention and remedy of insulin resistance.
据报道,无论是食欲肽神经肽甘丙肽还是食欲激素瘦素,都可以通过增加糖尿病患者葡萄糖转运蛋白 4(GLUT4)的易位来提高胰岛素敏感性。迄今为止,尚不清楚甘丙肽是否可以增强瘦素缓解胰岛素抵抗的作用。因此,在本研究中,我们试图评估中枢瘦素和甘丙肽联合对 2 型糖尿病大鼠脂肪组织胰岛素抵抗的影响。分别向糖尿病大鼠的侧脑室注射甘丙肽和瘦素,或每天合作注射一次,持续 2 周。然后,检查了几个胰岛素抵抗指标。结果表明,在高胰岛素-正葡萄糖钳夹试验中,葡萄糖输注率、血浆脂联素含量和脂肪细胞中 Akt 磷酸化以及 GLUT4 易位升高,而不是 GLUT4 蛋白和 GLUT4mRNA 表达,但甘丙肽+瘦素组的 HOMA 指数低于其中任何一种。此外,用 Akt 抑制剂 MK-2206 处理可阻断甘丙肽+瘦素联合对胰岛素抵抗的缓解作用。这些结果表明,甘丙肽可以改善瘦素诱导的脂肪细胞胰岛素抵抗缓解作用,为预防和治疗胰岛素抵抗提供了新的思路。