Insulin action at a molecular level - 100 years of progress

Mol Metab. 2021 Oct:52:101304. doi: 10.1016/j.molmet.2021.101304. Epub 2021 Jul 15.

Abstract

The discovery of insulin 100 years ago and its application to the treatment of human disease in the years since have marked a major turning point in the history of medicine. The availability of purified insulin allowed for the establishment of its physiological role in the regulation of blood glucose and ketones, the determination of its amino acid sequence, and the solving of its structure. Over the last 50 years, the function of insulin has been applied into the discovery of the insulin receptor and its signaling cascade to reveal the role of impaired insulin signaling-or resistance-in the progression of type 2 diabetes. It has also become clear that insulin signaling can impact not only classical insulin-sensitive tissues, but all tissues of the body, and that in many of these tissues the insulin signaling cascade regulates unexpected physiological functions. Despite these remarkable advances, much remains to be learned about both insulin signaling and how to use this molecular knowledge to advance the treatment of type 2 diabetes and other insulin-resistant states.

Keywords: Insulin; Insulin receptor; Insulin resistance; Insulin signal transduction.

Publication types

  • Historical Article
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Blood Glucose / metabolism
  • Brain / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / history
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Disease Models, Animal
  • Endothelium, Vascular / metabolism
  • Feedback, Physiological
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Insulin / administration & dosage
  • Insulin / history
  • Insulin / metabolism*
  • Insulin Resistance*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Liver / metabolism
  • Muscle, Skeletal / metabolism
  • Receptor, Insulin / history
  • Receptor, Insulin / metabolism*
  • Signal Transduction

Substances

  • Blood Glucose
  • Insulin
  • Receptor, Insulin