The one-inch-long zebrafish has become a valuable model for understanding development and human disease. Now, researchers at Vanderbilt University have created a zebrafish model of skeletal muscle insulin resistance that could help improve diabetes treatment.
Reporting in the American Journal of Physiology – Endocrinology and Metabolism, Wenbiao Chen, Ph.D., and colleagues describe what they consider to be the first direct demonstration of insulin-stimulated glucose uptake in the zebrafish.
When glucose uptake by muscle is impaired by transgenic, tissue-specific expression of a dominant negative type 1 Insulin-like Growth Factor receptor (IGF1r), the number of insulin-producing beta cells initially increases to compensate, then falls off as the animal ages.
These older animals have impaired glucose clearance but their fasting blood glucose is not elevated, indicating relatively slow progression from insulin resistance to glucose intolerance.
This model has “the potential in the future to test cooperating genes or metabolic conditions that may accelerate the development of diabetes and provide new therapeutic targets,” the researchers concluded.
The study was supported in part by National Institutes of Health grants DK088686 and DK002593.
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