Insulin: A 100-Year-Old Discovery With a Fascinating History

Abstract

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.

Amyloid Fibrillation of Insulin: Amelioration Strategies and Implications for Translation

“…Such a deteriorating landscape has naturally made insulin a therapeutically relevant biomacromolecule (Figure A). It is even more pertinent now as the global research community celebrates the centenary year of the discovery of insulin by the Canadian researchers Frederick Banting, Charles Best, John Macleod, and James Collip. , It is also fair to recognize the seminal prior work by the Romanian physiologist Nicolae Paulescu that contributed to the discovery . Later, insulin became the first protein to be fully sequenced by Frederick Sanger (Nobel Prize in Chemistry, 1958).…”

Metabolic hormones are integral regulators of female reproductive health and function

“…However, insulin levels are under multifactorial control, and autonomic nervous system innervation as well as other hormones (such as growth hormone and glucagon-like peptide 1) also affect insulin production and secretion; circulating levels are further controlled at the level of its clearance [ 200–203 ]. Insulin was discovered in 1921-22 with the extraction and purification of a pancreatic substance that could effectively lower blood glucose levels in patients with Type 1 diabetes [ 204 , 205 ]. It had a transformative impact on the treatment of diabetes, establishing its fundamental metabolic role.…”

Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis

“…Insulin is produced by pancreatic β-cells and acts as a major anabolic hormone in the control of glucose, lipid, and protein homeostasis 1 , 2 . At the cellular level, these effects are mediated by the insulin receptor (IR) and its intrinsic tyrosine kinase activity, which is activated by ligand binding.…”