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A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform
Published on: July 16, 2016
Insulin and glucagon regulate pancreatic α-cell proliferation
Zhuo Liu1, Wook Kim, Zhike Chen
1National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.
Plos One
|February 2, 2011
Summary
In type 2 diabetes, pancreatic alpha cell numbers increase, raising glucagon levels. Both insulin and glucagon act as growth factors for alpha cells, suggesting new therapeutic targets.
Area of Science:
- Endocrinology
- Metabolic Diseases
- Cell Biology
Background:
- Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, beta-cell dysfunction, and hyperglucagonemia.
- Excessive glucagon from pancreatic alpha cells drives hepatic glucose production, worsening hyperglycemia.
Purpose of the Study:
- To investigate whether alpha cell numbers increase in T2DM.
- To identify factors regulating alpha cell turnover in T2DM.
- To explore potential therapeutic strategies targeting alpha cells and glucagon.
Main Methods:
- Utilized Lepr(db)/Lepr(db) (db/db) mice as a T2DM model.
- Employed αTC1 cells to study alpha cell trophic factors.
- Administered insulin and glucagon receptor (GcgR) antagonists.
Main Results:
- Alpha cell number and plasma glucagon levels increased with diabetes progression in db/db mice.
- Insulin treatment stimulated alpha cell proliferation via the IR/IRS2/AKT/mTOR pathway.
- Glucagon receptor antagonism improved glucose homeostasis and reduced alpha cell proliferation in db/db mice.
Conclusions:
- Pancreatic alpha cell proliferation increases in T2DM, contributing to elevated glucagon.
- Both insulin and glucagon act as trophic factors for alpha cells.
- Targeting alpha cells and glucagon presents a potential therapeutic avenue for T2DM.
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