Burcelin R, Katz E B, Charron M J
Biochemistry Dept., Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Diabetes Metab. 1996 Dec;22(6):373-96.
The role of glucagon in eliciting hyperglycaemia has been studied extensively for more than 20 years. However, little has been learned about the specific targeted tissues and intracellular effects of glucagon since no specific causal interactions have been established between glucagon and the so called "glucagon-binding site". Indeed, glucagon and related hormones, such as glucagon-like peptide, glucoin-sulinotropic hormone and vasoactive intestinal peptide acting through different receptors, have similar effects in hyperglycaemic syndromes. The recent cloning of the glucagon receptor (GR) encoding sequences has clarified many aspects of its structure as well as its integrated role in the cell and the entire body. The GR contains seven transmembrane domains and is characterised by a conserved G-protein binding site and a large amino-terminal domain containing the amino-acid residues mainly involved in ligand binding. The GR is expressed in liver, pancreatic beta cells, kidney, adipose tissues, heart, and vascular tissues, as well as in some region of brain, stomach, and adrenal glands. The precise role of the GR in most of these tissues is still unclear. However, with the cloning of the coding sequences, genetic manipulations of the GR should provide specific indications of the normal metabolic effects of the GR system on these tissues and how altered glucagon signalling might contribute to the development of diabetes.
二十多年来，人们对胰高血糖素在引发高血糖症中的作用进行了广泛研究。然而，由于尚未在胰高血糖素与所谓的“胰高血糖素结合位点”之间建立特定的因果相互作用，因此对于胰高血糖素的特定靶组织和细胞内效应了解甚少。实际上，胰高血糖素及相关激素，如胰高血糖素样肽、促葡萄糖胰岛素释放肽和血管活性肠肽，通过不同受体发挥作用，在高血糖综合征中具有相似的作用。最近胰高血糖素受体（GR）编码序列的克隆阐明了其结构的许多方面以及它在细胞和整个身体中的综合作用。GR含有七个跨膜结构域，其特征在于保守的G蛋白结合位点和一个大的氨基末端结构域，该结构域包含主要参与配体结合的氨基酸残基。GR在肝脏、胰腺β细胞、肾脏、脂肪组织、心脏和血管组织中表达，以及在大脑、胃和肾上腺的一些区域中表达。GR在这些组织中的大多数的确切作用仍不清楚。然而，随着编码序列的克隆，对GR的基因操作应该能够提供关于GR系统对这些组织的正常代谢作用以及胰高血糖素信号改变如何可能导致糖尿病发展的具体指示。
