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Updated: Dec 3, 2025

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Translational Factor eIF4G1 Regulates Glucose Homeostasis and Pancreatic β-Cell Function.

Seokwon Jo1, Amber Lockridge1, Ramkumar Mohan1

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The translational factor eIF4G1 is crucial for maintaining glucose homeostasis and pancreatic beta-cell function. Its absence impairs insulin secretion and biosynthesis, highlighting its role in diabetes.

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Area of Science:

  • Cell Biology
  • Metabolism
  • Endocrinology

Background:

  • Protein translation is vital for cellular function, and its dysregulation is linked to aging-related diseases like type 2 diabetes.
  • Reduced levels of the initiation factor eIF4G1 are associated with diabetes in humans and mice.

Purpose of the Study:

  • To investigate the critical role of eIF4G1 in pancreatic beta-cell function and glucose homeostasis.
  • To test the hypothesis that eIF4G1 is essential for maintaining normal beta-cell physiology and glucose metabolism in vivo.

Main Methods:

  • Generation of a specific beta-cell eIF4G1 knockout (βeIF4G1KO) mouse model.
  • Assessment of glucose tolerance, insulin sensitivity, beta-cell mass, proliferation, and apoptosis.
  • Analysis of insulin secretion, mitochondrial function, calcium flux, and eIF4E levels.

Main Results:

  • βeIF4G1KO mice exhibited glucose intolerance but normal insulin sensitivity.
  • Beta-cell mass remained normal, but proliferation and apoptosis increased.
  • Deficits in insulin secretion were linked to reduced mitochondrial respiration, impaired Ca2+ flux, and decreased insulin content due to eIF4E loss.
  • Restoring eIF4E in βeIF4G1KO mice recovered insulin content.

Conclusions:

  • The translational factor eIF4G1 plays an essential role in glucose homeostasis and beta-cell function.
  • eIF4G1/eIF4E interaction is critical for insulin biosynthesis and secretion.
  • These findings reveal an unexplored role for eIF4G1 in regulating beta-cell function and metabolism.