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The New Biology and Pharmacology of Glucagon.
Physiological Reviews ( IF 33.6 ) Pub Date : 2017-03-10 , DOI: 10.1152/physrev.00025.2016
T D Müller 1 , B Finan 1 , C Clemmensen 1 , R D DiMarchi 1 , M H Tschöp 1
Affiliation  

In the last two decades we have witnessed sizable progress in defining the role of gastrointestinal signals in the control of glucose and energy homeostasis. Specifically, the molecular basis of the huge metabolic benefits in bariatric surgery is emerging while novel incretin-based medicines based on endogenous hormones such as glucagon-like peptide 1 and pancreas-derived amylin are improving diabetes management. These and related developments have fostered the discovery of novel insights into endocrine control of systemic metabolism, and in particular a deeper understanding of the importance of communication across vital organs, and specifically the gut-brain-pancreas-liver network. Paradoxically, the pancreatic peptide glucagon has reemerged in this period among a plethora of newly identified metabolic macromolecules, and new data complement and challenge its historical position as a gut hormone involved in metabolic control. The synthesis of glucagon analogs that are biophysically stable and soluble in aqueous solutions has promoted biological study that has enriched our understanding of glucagon biology and ironically recruited glucagon agonism as a central element to lower body weight in the treatment of metabolic disease. This review summarizes the extensive historical record and the more recent provocative direction that integrates the prominent role of glucagon in glucose elevation with its under-acknowledged effects on lipids, body weight, and vascular health that have implications for the pathophysiology of metabolic diseases, and the emergence of precision medicines to treat metabolic diseases.

中文翻译:

胰高血糖素的新生物学和药理学。

在过去的二十年中,我们见证了在确定胃肠道信号在控制葡萄糖和能量稳态中的作用方面取得了巨大进展。具体来说,减肥手术中巨大的代谢益处的分子基础正在兴起,而基于内分泌激素的新的基于肠降血糖素的药物(例如胰高血糖素样肽1和胰腺衍生的胰岛淀粉样多肽)正在改善糖尿病的管理。这些和相关的发展促进了对内分泌控制系统代谢的新颖见解的发现,尤其是对跨重要器官,特别是肠脑-胰腺-肝网络进行交流的重要性的更深了解。矛盾的是,在这一时期,胰肽胰高血糖素重新出现在大量新发现的代谢大分子中,新数据补充并挑战了其作为参与代谢控制的肠道激素的历史地位。具有生物物理稳定性并且可溶于水溶液的胰高血糖素类似物的合成促进了生物学研究,该研究丰富了我们对胰高血糖素生物学的理解,并且具有讽刺意味的是,胰高血糖素激动作用是降低代谢性疾病体重的重要因素。这篇综述总结了广泛的历史记录和最近的挑衅性方向,将胰高血糖素在葡萄糖升高中的突出作用与其对脂质,体重和血管健康的未充分认识的影响相结合,这些影响对代谢疾病的病理生理学和精密药物治疗代谢性疾病的出现。
更新日期:2019-11-01
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