Lund Asger, Bagger Jonatan I, Christensen Mikkel, Knop Filip K, Vilsbøll Tina
Center for Diabetes Research, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Curr Diab Rep. 2014 Dec;14(12):555. doi: 10.1007/s11892-014-0555-4.
In normal physiology, glucagon from pancreatic alpha cells plays an important role in maintaining glucose homeostasis via its regulatory effect on hepatic glucose production. Patients with type 2 diabetes suffer from fasting and postprandial hyperglucagonemia, which stimulate hepatic glucose production and, thus, contribute to the hyperglycemia characterizing these patients. Although this has been known for years, research focusing on alpha cell (patho)physiology has historically been dwarfed by research on beta cells and insulin. Today the mechanisms behind type 2 diabetic hyperglucagonemia are still poorly understood. Preclinical and clinical studies have shown that the gastrointestinal hormone glucose-dependent insulinotropic polypeptide (GIP) might play an important role in this pathophysiological phenomenon. Furthermore, it has become apparent that suppression of glucagon secretion or antagonization of the glucagon receptor constitutes potentially effective treatment strategies for patients with type 2 diabetes. In this review, we focus on the regulation of glucagon secretion by the incretin hormones glucagon-like peptide-1 (GLP-1) and GIP. Furthermore, potential advantages and limitations of suppressing glucagon secretion or antagonizing the glucagon receptor, respectively, in the treatment of patients with type 2 diabetes will be discussed.
在正常生理状态下，胰腺α细胞分泌的胰高血糖素通过对肝脏葡萄糖生成的调节作用，在维持葡萄糖稳态方面发挥着重要作用。2型糖尿病患者存在空腹和餐后高胰高血糖素血症，这会刺激肝脏葡萄糖生成，进而导致这些患者出现高血糖症状。尽管这一情况已为人所知多年，但历史上专注于α细胞（病理）生理学的研究与针对β细胞和胰岛素的研究相比显得微不足道。如今，2型糖尿病高胰高血糖素血症背后的机制仍知之甚少。临床前和临床研究表明，胃肠激素葡萄糖依赖性促胰岛素多肽（GIP）可能在这一病理生理现象中发挥重要作用。此外，显而易见的是，抑制胰高血糖素分泌或拮抗胰高血糖素受体对2型糖尿病患者构成了潜在有效的治疗策略。在本综述中，我们聚焦于肠促胰岛素激素胰高血糖素样肽-1（GLP-1）和GIP对胰高血糖素分泌的调节作用。此外，还将分别讨论抑制胰高血糖素分泌或拮抗胰高血糖素受体在2型糖尿病患者治疗中的潜在优势和局限性。
