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Mouse models of insulin resistance
Marta Letizia Hribal1, Francesco Oriente, Domenico Accili
1Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians & Surgeons of Columbia University, New York, New York 10032, USA.
Summary
Type 2 diabetes involves insulin resistance and beta-cell dysfunction. Recent research suggests insulin signaling
Area of Science:
- Endocrinology and Metabolism
- Molecular Biology
Background:
- Type 2 diabetes is characterized by insulin resistance in peripheral tissues and impaired pancreatic beta-cell function.
- Traditionally, these defects were considered separate, with insulin resistance linked to skeletal muscle glucose uptake and beta-cell dysfunction to impaired insulin secretion.
Purpose of the Study:
- To re-evaluate the role of insulin signaling in the pathogenesis of type 2 diabetes.
- To reconcile controversies surrounding insulin signaling in skeletal muscle and pancreatic beta-cells.
Main Methods:
- Review of recent progress in understanding insulin action pathways.
- Analysis of targeted mutagenesis and transgenesis studies involving insulin signaling components.
Main Results:
- The role of insulin signaling in classic target tissues like skeletal muscle may have been overestimated.
- Insulin signaling in the liver, pancreatic beta-cells, and brain appears more critical than previously thought.
Conclusions:
- A revised understanding of insulin signaling is crucial for type 2 diabetes research.
- Focusing on liver, beta-cells, and brain may offer new therapeutic targets for type 2 diabetes.