Historical Background of Pancreatic Islet Isolation

Abstract

Until the discovery of insulin in the twentieth century, diabetes mellitus was a mortal disease with an unclear origin and physiology. Despite the appearance of the concept in an Egyptian papyrus dated c.1550 BC, and the documentation of its study by ancient Chinese, the term "diabetes" was only coined by the Greek Aretaeus in the second century AD. In Europe, the study of diabetes was largely ignored until the seventeenth century, when the characteristic sweet flavor of diabetic urine was first described. However, the link between diabetes and the pancreas was not discovered until 1889 by Minkowski and von Mering, long after the first description of the pancreatic islets by Paul Langerhans in 1869. One of the most significant milestones in the field was the discovery of insulin by Banting and collaborators in 1922, which led to the therapeutic development of insulin administration as a life-saving intervention for type 1 diabetic patients. On the other hand, the isolation of islets was first reported by Bensley in 1911, a critical technical achievement that paved the way for clinical islet transplantation. Here we discuss the history of islet isolation, since the firsts studies of diabetes by ancient civilizations to the birth and parallel evolution of islet isolation and transplantation.

The Future of Islet Transplantation Is Now

“…Physicians from antiquity knew of a disease that caused excessive output of urine that had sweetness to it, that today we would call diabetes mellitus. Medical literature from the great centers of learning in the ancient world including Egypt, China, and India documented early attempts to categorize this disease ( 1 , 2 ). By 150 AD, the Greek physician Arateus was able to provide a recognizable diagnosis and coined the name diabetes (meaning siphon) ( 1 – 3 ).…”

“…While the honey-like sweetness ( mel, mellis ) of urine had long been associated with diabetes, [mellitus being added to the name in late seventeenth century ( 1 , 2 , 4 ), it was not until 1776 that Matthew Dobson was able to scientifically demonstrate excess sugar in the urine of those effected by the disease in his famous series of experiments, by boiling urine to dryness and observing the crystalized remains ( 1 , 2 , 4 ). In 1850 Claude Bernard discovered a substance in the liver that he named glycogen, which was converted into glucose and then secreted into the blood, an action that he believed to be the cause of diabetes ( 1 , 2 , 4 ). The second half of the nineteenth century saw scientific discussions centered on whether the primary cause of diabetes rested in the kidney or the pancreas.…”

“…The second half of the nineteenth century saw scientific discussions centered on whether the primary cause of diabetes rested in the kidney or the pancreas. German physiologist Paul Langerhans first described the cells that would eventually be known as islets of Langerhans in 1869, although it would be left to others, years later, to determine their purpose ( 2 , 5 ). In 1882, Oskar Minkowski and Joseph von Mering definitively concluded that diabetes was a disease of the pancreas by removing the pancreas from a dog, leading to diabetes.…”

“…In 1882, Oskar Minkowski and Joseph von Mering definitively concluded that diabetes was a disease of the pancreas by removing the pancreas from a dog, leading to diabetes. Transplantation of autologous pancreatic fragments under the skin showed transient improvement in glycosuria ( 1 , 2 , 6 ). Many experiments were conducted even into the twentieth century in which pancreatic fragments were transplanted into animals in mostly unsuccessful attempts to cure diabetes ( 7 , 8 ).…”

“…Beginning with the discovery of insulin by Frederick Banting and Charles Best in 1922 ( 1 , 2 , 9 ), for which Banting, but not Best, won a Nobel Prize the following year, diabetes went from being a terminal disease to a chronic one. Refinements in the understanding of the human insulin sequence eventually led to the production of recombinant human insulin which replaced animal extracted insulin ( 10 ).…”