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Deprogram and reprogram to solve the riddle of insulin resistance
Victoria L Tokarz1,2, Paul Delgado-Olguín3,4,5, Amira Klip1,2,6,7
1Cell Biology Program, The Hospital for Sick Children, Toronto, Canada.
The Journal of Clinical Investigation
|November 1, 2021
Summary
Researchers used stem cell-derived muscle cells to find molecular differences linked to insulin resistance. These changes, present even without insulin, suggest genetic factors influence how well the body handles blood sugar, impacting type 2 diabetes risk.
Area of Science:
- Biochemistry
- Genetics
- Endocrinology
Background:
- Skeletal muscle plays a key role in regulating blood glucose levels.
- The molecular mechanisms and genetic factors underlying insulin resistance progression to type 2 diabetes are not fully understood.
Purpose of the Study:
- To investigate molecular differences in insulin sensitivity using induced pluripotent stem cell-derived myoblasts (iMyos).
- To identify sex- and population-based variations in phosphoproteomic profiles related to insulin sensitivity.
Main Methods:
- Utilized induced pluripotent stem cell-derived myoblasts (iMyos) as a model system.
- Performed phosphoproteomic analysis to compare differences between sexes and insulin sensitivity quintiles in a healthy population.
- Examined molecular changes in both basal and insulin-stimulated states.
Main Results:
- Identified numerous phosphoproteomic differences between sexes and insulin sensitivity groups.
- Observed significant phosphoproteomic variations even in the absence of insulin, indicating a role for basal cellular states.
- Found that deficiencies in iPSCs and iMyos may involve genetic and epigenetic factors influencing insulin sensitivity.
Conclusions:
- Basal cellular phosphoproteomic landscapes significantly impact insulin action efficiency.
- Genetic and epigenetic factors likely play a crucial role in modulating insulin sensitivity and the development of insulin resistance.
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