Insulin biosynthetic interaction network component, TMEM24, facilitates insulin reserve pool release

Area of Science:

• Cell biology
• Proteomics
• Endocrinology

Background:

• Insulin homeostasis in pancreatic beta cells is vital for metabolic health.
• Dysregulation of insulin secretion is implicated in obesity and type II diabetes (T2D).
• The proteins interacting with insulin during its biosynthesis and secretion are largely uncharacterized.

Purpose of the Study:

• To generate a comprehensive proteomic map of insulin's sequential interacting partners in pancreatic beta cells.
• To identify novel proteins involved in the insulin secretory pathway.
• To elucidate the molecular mechanisms underlying glucose-stimulated insulin secretion.

Main Methods:

• Utilized a conformation-based approach combined with mass spectrometry.
• Developed the insulin biosynthetic interaction network (insulin BIN) to chart protein interactions along the insulin secretory axis.
• Investigated the role of identified proteins in insulin secretion.

Main Results:

• Generated the insulin BIN, a proteomic roadmap of sequential insulin-binding partners.
• Identified TMEM24 (transmembrane protein 24) as an abundant protein interacting with insulin.
• TMEM24 was found to manage glucose-stimulated insulin secretion from a reserve granule pool.

Conclusions:

• The insulin BIN provides a molecular description of the insulin secretory pathway in beta cells.
• TMEM24 plays a critical role in regulating insulin secretion, a process impaired in type II diabetes.
• This study identifies key molecular players in insulin homeostasis and secretion, offering potential therapeutic targets for T2D.