饥饿素在糖代谢中的作用以及在糖尿病中的研究综述

Review on the Role of Ghrelin in Glucose Metabolism and Diabetes Mellitus

摘要: 饥饿素(Ghrelin)是1999年发现的一种28氨基酸(AA)胃源性肽，是生长激素促分泌受体(GHSR)的内源性配体。能够分泌Ghrelin的细胞构成一组组功能独特的内分泌细胞群，主要分布于胃粘膜，在小肠和内分泌胰腺中较少。空腹和热量限制摄入(如少食)期间，血浆Ghrelin水平升高，以刺激食物摄入和脂肪储存，防止的血糖进一步下降，进而危及生命。餐后及能量过剩(如肥胖)时，血浆Ghrelin水平降低，其血糖调节功能不明显。最新研究表明，Ghrelin已成为调节食欲和能量平衡的关键因子，Ghrelin通过在食欲调节神经元和包括内分泌胰腺在内的外周代谢器官中结合Ghrelin受体GHSR来实现这些功能。Ghrelin水平与体重指数(BMI)和胰岛素抵抗呈负相关。一些研究强调Ghrelin在葡萄糖稳态中的重要作用。基因、免疫和药物阻断Ghrelin信号导致糖耐量和胰岛素敏感性的改善。此外，外源性Ghrelin给药可降低葡萄糖诱导的胰岛素释放，提高人和实验动物血浆的葡萄糖水平。GHSR可以在胰腺β细胞中稳定表达，Ghrelin通过Ca²⁺通道抑制胰岛素释放。Ghrelin对糖代谢和脂质稳态的影响可能为治疗肥胖相关的2型糖尿病和相关代谢功能障碍新的靶点，进而提供新的预防或早期干预治疗策略。本综述着眼于探究Ghrelin在机体糖代谢的作用，以及与糖尿病的相关性，从而明确Ghrelin在糖尿病中的作用，进而为糖尿病的治疗提供新的思路和方法。

Abstract: Ghrelin is a 28 amino acid (AA) gastrointestinal peptide discovered in 1999. It is an endogenous ligand of growth hormone secretagogue receptor (GHSR). Cells which can secrete ghrelin to constitute a group of endocrine cells with unique functions, mainly distributed in the gastric mucosa, but less in the small intestine and endocrine pancreas. During fasting and caloric restriction (such as eating less), the levels of plasma ghrelin l are elevated to stimulate food intake and fat storage, preventing a further drop in blood sugar that can be life-threatening. Plasma ghrelin levels are reduced after meal and in excess energy (e.g., obesity), and its glycemic regulation function is not obvious. Recent studies have shown that ghrelin has become a key factor in regulating appetite and energy balance. It can achieve those functions by binding itself to the GHSR receptor both in appetite regulating neurons and in peripheral metabolic organs, including the endocrine pancreas. Ghrelin levels were negatively correlated with body mass index (BMI) and insulin resistance. Some studies have highlighted the important role of ghrelin in glucose homeostasis. Gene, immune and drug blocking ghrelin signal led to improved glucose tolerance and insulin sensitivity. In addition, the administration of exogenous ghrelin can reduce glucose-induced insulin release and increase the plasma glucose level of human beings and experimental animals. GHSR is stably expressed in beta cells of the pancreas, and ghrelin inhibits insulin release through Ca²⁺ channels. The effect of ghrelin on glucose metabolism and lipid homeostasis may be a new target for the treatment of obesity-related type 2 diabetes and related metabolic dysfunction, thus providing new prevention or early intervention strategies. This review aims to explore the role of ghrelin in the body’s glucose metabolism and its correlation with diabetes, so as to clarify the role of ghrelin in diabetes, and thus provide new ideas and methods for the treatment of diabetes.