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Publication
Skeletal muscle insulin resistance in zebrafish induces alterations in ß-cell
number and glucose tolerance in an age- and diet-dependent manner.
Authors Maddison LA, Joest KE, Kammeyer RM, Chen W
Submitted By Submitted Externally on 7/24/2015
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2015
Date Published 4/15/2015
Volume : Pages 308 : E662 - E669
PubMed Reference 25670827
Abstract Insulin resistance creates an environment that promotes ß-cell failure and
development of diabetes. Understanding the events that lead from insulin
resistance to diabetes is necessary for development of effective preventional
and interventional strategies, and model systems that reflect the
pathophysiology of disease progression are an important component toward this
end. We have confirmed that insulin enhances glucose uptake in zebrafish
skeletal muscle and have developed a zebrafish model of skeletal muscle insulin
resistance using a dominant-negative IGF-IR. These zebrafish exhibit blunted
insulin signaling and glucose uptake in the skeletal muscle, confirming insulin
resistance. In young animals, we observed an increase in the number of ß-cells
and normal glucose tolerance that was indicative of compensation for insulin
resistance. In older animals, the ß-cell mass was reduced to that of control
with the appearance of impaired glucose clearance but no elevation in fasting
blood glucose. Combined with overnutrition, the insulin-resistant animals have
an increased fasting blood glucose compared with the control animals,
demonstrating that the ß-cells in the insulin-resistant fish are in a vulnerable
state. The relatively slow progression from insulin resistance to glucose
intolerance in this model system 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.




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