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Translational Factor eIF4G1 Regulates Glucose Homeostasis and Pancreatic β-Cell Function
- Source :
- Diabetes
- Publication Year :
- 2020
-
Abstract
- Protein translation is essential for cell physiology, and dysregulation of this process has been linked to aging-related diseases such as type 2 diabetes. Reduced protein level of a requisite scaffolding protein of the initiation complex, eIF4G1, downstream of nutrients and insulin signaling is associated with diabetes in humans and mice. In the current study, we tested the hypothesis that eIF4G1 is critical for β-cell function and glucose homeostasis by genetically ablating eIF4G1 specifically in β-cells in vivo (βeIF4G1 knockout [KO]). Adult male and female βeIF4G1KO mice displayed glucose intolerance but normal insulin sensitivity. β-Cell mass was normal under steady state and under metabolic stress by diet-induced obesity, but we observed increases in proliferation and apoptosis in β-cells of βeIF4G1KO. We uncovered deficits in insulin secretion, partly due to reduced mitochondrial oxygen consumption rate, glucose-stimulated Ca2+ flux, and reduced insulin content associated with loss of eIF4E, the mRNA 5′ cap-binding protein of the initiation complex and binding partner of eIF4G1. Genetic reconstitution of eIF4E in single β-cells or intact islets of βeIF4G1KO mice recovers insulin content, implicating an unexplored role for eIF4G1/eIF4E in insulin biosynthesis. Altogether these data demonstrate an essential role for the translational factor eIF4G1 on glucose homeostasis and β-cell function.
- Subjects :
- 0301 basic medicine
Cell physiology
Male
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
030209 endocrinology & metabolism
Type 2 diabetes
Carbohydrate metabolism
03 medical and health sciences
Mice
0302 clinical medicine
Oxygen Consumption
Diabetes mellitus
Insulin-Secreting Cells
Glucose Intolerance
Insulin Secretion
Internal Medicine
medicine
Glucose homeostasis
Animals
Homeostasis
Calcium Signaling
Mice, Knockout
biology
Chemistry
Insulin
EIF4E
medicine.disease
Cell biology
Mitochondria
Insulin receptor
030104 developmental biology
Glucose
Islet Studies
biology.protein
Female
Eukaryotic Initiation Factor-4G
Subjects
Details
- ISSN :
- 1939327X
- Volume :
- 70
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....2895145131aaae287aaff661f488c271