Rostène William, De Meyts Pierre
Sorbonne Université, INSERM, CNRS, Institut de la Vision, F-75012 Paris, France.
de Duve Institute, B-1200 Brussels, Belgium.
Endocr Rev. 2021 Sep 28;42(5):503-527. doi: 10.1210/endrev/bnab020.
Diabetes has been known since antiquity. We present here a historical perspective on the concepts and ideas regarding the physiopathology of the disease, on the progressive focus on the pancreas, in particular on the islets discovered by Langerhans in 1869, leading to the iconic experiment of Minkowski and von Mering in 1889 showing that pancreatectomy in a dog induced polyuria and diabetes mellitus. Subsequently, multiple investigators searched for the active substance of the pancreas and some managed to produce extracts that lowered blood glucose and decreased polyuria in pancreatectomized dogs but were too toxic to be administered to patients. The breakthrough came 100 years ago, when the team of Frederick Banting, Charles Best, and James Collip working in the Department of Physiology headed by John Macleod at the University of Toronto managed to obtain pancreatic extracts that could be used to treat patients and rescue them from the edge of death by starvation, the only treatment then available. This achievement was quickly recognized by the Nobel Prize in Physiology or Medicine to Banting and Macleod in 1923. At 32, Banting remains the youngest awardee of this prize. Here we discuss the work that led to the discovery and its main breakthroughs, the human characters involved in an increasingly dysfunctional relationship, the controversies that followed the Nobel Prize, and the debate as to who actually "discovered" insulin. We also discuss the early commercial development and progress in insulin crystallization in the decade or so following the Nobel Prize.
糖尿病自古以来便为人所知。在此，我们呈现关于该疾病生理病理学概念和观点的历史视角，以及对胰腺关注度的逐步提升，特别是对1869年由朗格汉斯发现的胰岛的关注，这最终促成了1889年明科夫斯基和冯·梅林的标志性实验，该实验表明切除狗的胰腺会导致多尿和糖尿病。随后，众多研究者探寻胰腺的活性物质，一些人成功制备出能降低切除胰腺的狗的血糖并减少多尿的提取物，但这些提取物毒性过大，无法用于患者。100年前取得了突破，当时在多伦多大学约翰·麦克劳德领导的生理学系工作的弗雷德里克·班廷、查尔斯·贝斯特和詹姆斯·科利普团队成功获得了可用于治疗患者并将他们从饥饿导致的死亡边缘拯救回来的胰腺提取物，而饥饿是当时唯一可用的治疗方法。这一成就很快在1923年为班廷和麦克劳德赢得了诺贝尔生理学或医学奖。32岁的班廷至今仍是该奖项最年轻的获得者。在此，我们讨论促成这一发现的工作及其主要突破、涉及一段日益失调关系的人物、诺贝尔奖之后的争议，以及关于究竟是谁“发现”了胰岛素的争论。我们还讨论了诺贝尔奖之后大约十年里胰岛素结晶方面的早期商业发展和进展。
