Synthalin: a lost lesson for glucagon suppression in diabetes therapeutics

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. 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.

Automated summary

This short review examines the early studies performed with Syn A in animals and diabetic patients, finding that excess glucagon secretion from pancreatic alpha-cells is a problem in both type 1 and type 2 diabetes. Therefore, therapeutic strategies aimed at limiting the number or function of alpha-cells might be worthy of reconsideration.