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Glycogen synthase: a putative locus for diet-induced hyperglycemia
1Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
The Journal of Clinical Investigation
|July 1, 1994
Summary
Genetic mapping in mice identified chromosome 7 regions linked to type 2 diabetes traits. Defects in the glycogen synthase gene (Gys) may contribute to diabetes susceptibility, offering insights into human disease.
Area of Science:
- Genetics
- Metabolic Disease Research
- Animal Models
Background:
- Inbred mouse strains exhibit varying susceptibility to type 2 diabetes mellitus (T2DM) features when fed a diabetogenic diet.
- Understanding the genetic basis of T2DM susceptibility is crucial for developing targeted interventions.
Purpose of the Study:
- To identify chromosomal locations controlling T2DM-related traits, specifically insulin levels and hyperglycemia.
- To investigate the role of the glycogen synthase gene (Gys) as a potential T2DM susceptibility locus.
Main Methods:
- Utilized recombinant inbred strains derived from diabetes-prone C57BL/6J (B/6J) and diabetes-resistant A/J mouse strains.
- Performed genetic linkage analysis on mouse chromosome 7 to correlate insulin levels and hyperglycemia with specific markers.
- Assessed fractional glycogen synthase activity in isolated muscle tissue.
Main Results:
- Two distinct regions on mouse chromosome 7 were significantly associated with insulin levels and hyperglycemia.
- A region containing the tubby mutation showed concordance with insulin levels.
- The D7Mit25 marker and Gpi-1 locus on proximal chromosome 7 were linked to hyperglycemia, consistent with the Gys gene locus.
- Lower fractional glycogen synthase activity was observed in diabetic-prone B/6J mice compared to resistant A/J mice.
Conclusions:
- Genetic loci on mouse chromosome 7 influence susceptibility to T2DM-like phenotypes.
- The glycogen synthase gene (Gys) is a strong candidate for a T2DM susceptibility gene.
- Reduced glycogen synthase activity may contribute to the propensity for developing type 2 diabetes.
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