Márquez L, González N, Puente J, Valverde L, Villanueva-Peñacarrillo M L
Department of Metabolism, Nutrition and Hormones, Fundación Jiménez Díaz, Madrid, Spain.
Diabetes Nutr Metab. 2001 Oct;14(5):239-44.
GLP-1 (glucagon-like peptide 1), proposed as a possible tool for Type 2 diabetes therapy, has insulin-like effects upon glucose metabolism in extrapancreatic tissues, whose plasma membranes contain specific receptors for the peptide, being those, at least in liver and muscle, not associated to the adenylate cyclase/cAMP system. GLP-1, as insulin, modulates the content of glycosylphosphatidylinositols (GPIs)--precursors of inositolphosphoglycans (IPGs), considered mediators of insulin action--in several extrapancreatic cell lines and in normal rat hepatocytes and adipocytes. In the present paper, we document that in a streptozotocin-induced Type 2 diabetic rat model, GLP-1, as insulin, provokes a rapid decrease of the [myo-3H-inositol]GPI content in isolated adipocytes--indicative of its hydrolysis and immediate short-lived generation of IPG--as that previously observed in normal animals; in hepatocytes, GLP-1, but not insulin, induced a reduction in the cellular GPI, although delayed in relation to normal rats. In adipocytes from streptozotocin-induced Type 1 diabetic rats, GLP-1, as insulin, seems to induce a reduction in the cellular GPI content, which was smaller and occurred later than that provoked in the Type 2 diabetic model; in the hepatocytes, GLP-1 and insulin failed to affect the control GPI content at any time tested. In Type 2 diabetic rat, the hepatocyte retains its response capability to GLP-1, but not to insulin, suggesting that the peptide could be bypassing possible defective steps in the insulin signaling pathway in the liver of this diabetic model.
胰高血糖素样肽-1（GLP-1）被认为是治疗2型糖尿病的一种可能工具，它对胰腺外组织的葡萄糖代谢具有胰岛素样作用，这些组织的质膜含有该肽的特异性受体，至少在肝脏和肌肉中，这些受体与腺苷酸环化酶/cAMP系统无关。与胰岛素一样，GLP-1可调节几种胰腺外细胞系以及正常大鼠肝细胞和脂肪细胞中糖基磷脂酰肌醇（GPI）的含量，GPI是肌醇磷酸聚糖（IPG）的前体，被认为是胰岛素作用的介质。在本文中，我们证明，在链脲佐菌素诱导的2型糖尿病大鼠模型中，与胰岛素一样，GLP-1可使分离的脂肪细胞中[肌醇-3H]GPI含量迅速降低，这表明其水解并立即短暂生成IPG，这与之前在正常动物中观察到的情况相同；在肝细胞中，GLP-1而非胰岛素可导致细胞GPI减少，尽管相对于正常大鼠有所延迟。在链脲佐菌素诱导的1型糖尿病大鼠的脂肪细胞中，与胰岛素一样，GLP-1似乎可导致细胞GPI含量降低，但其降低幅度较小且发生时间晚于2型糖尿病模型；在肝细胞中，GLP-1和胰岛素在任何测试时间均未影响对照GPI含量。在2型糖尿病大鼠中，肝细胞保留了对GLP-1的反应能力，但对胰岛素无反应，这表明该肽可能绕过了该糖尿病模型肝脏中胰岛素信号通路中可能存在缺陷的步骤。
