Synthalin: a lost lesson for glucagon suppression in diabetes therapeutics

J Pharm Pharmacol. 2023 Jun 5;75(6):758-763. doi: 10.1093/jpp/rgad010.

Abstract

Objectives: Within mammalian pancreatic islets, there are two major endocrine cell types, beta-cells which secrete insulin and alpha-cells which secrete glucagon. Whereas, insulin acts to lower circulating glucose, glucagon counters this by increasing circulating glucose via the mobilisation of glycogen. Synthalin A (Syn A) was the subject of much research in the 1920s and 1930s as a potential pancreatic alpha-cell toxin to block glucagon secretion. However, with the discovery of insulin and its lifesaving use in patients with diabetes, research on Syn-A was discontinued.

Key findings: This short review looks back on early studies performed with Syn A in animals and humans with diabetes. These are relevant today because both type 1 and type 2 diabetes are now recognised as states of not only insulin deficiency but also glucagon excess.

Summary: Lessons learned from this largely forgotten portfolio of work and therapeutic strategy aimed at limiting the number or function of islet alpha-cells might be worthy of reconsideration.

Keywords: Synthalin (Syn); alpha-cells; beta-cells; diabetes; glucagon; pancreatic islets.

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / metabolism
  • Glucagon / metabolism
  • Glucose / metabolism
  • Humans
  • Insulin / metabolism
  • Islets of Langerhans* / metabolism
  • Mammals / metabolism

Substances

  • Glucagon
  • Insulin
  • Glucose

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