PUBLICATION
Skeletal muscle insulin resistance in zebrafish induces alterations in β-cell number and glucose tolerance in an age and diet dependent manner
- Authors
- Maddison, L.A., Joest, K.E., Kammeyer, R.M., Chen, W.
- ID
- ZDB-PUB-150212-3
- Date
- 2015
- Source
- American journal of physiology. Endocrinology and metabolism 308(8): E662-9 (Journal)
- Registered Authors
- Chen, Wenbiao
- Keywords
- Diabetes, Insulin resistance, glucose intolerance, zebrafish, β-cell
- MeSH Terms
-
- Aging*
- Animals
- Animals, Genetically Modified
- Biological Transport
- Cell Count
- Disease Progression
- Glucose/metabolism
- Glucose Intolerance/etiology*
- Glucose Intolerance/metabolism
- Glucose Intolerance/pathology
- Glucose Intolerance/physiopathology
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Hyperglycemia/etiology
- Insulin/genetics
- Insulin/metabolism
- Insulin Resistance*
- Insulin-Like Growth Factor I/genetics
- Insulin-Like Growth Factor I/metabolism
- Insulin-Secreting Cells/metabolism
- Insulin-Secreting Cells/pathology*
- Luminescent Proteins/genetics
- Luminescent Proteins/metabolism
- Muscle, Skeletal/metabolism*
- Overnutrition/physiopathology*
- Receptor, IGF Type 1/genetics
- Receptor, IGF Type 1/metabolism*
- Recombinant Fusion Proteins/genetics
- Recombinant Fusion Proteins/metabolism
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 25670827 Full text @ Am. J. Physiol. Endocrinol. Metab.
Citation
Maddison, L.A., Joest, K.E., Kammeyer, R.M., Chen, W. (2015) Skeletal muscle insulin resistance in zebrafish induces alterations in β-cell number and glucose tolerance in an age and diet dependent manner. American journal of physiology. Endocrinology and metabolism. 308(8):E662-9.
Abstract
Insulin resistance creates an environment that promotes β-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 towards 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 IGF1r. 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 β-cells and normal glucose tolerance indicative of compensation for insulin resistance. In older animals the β-cell mass was reduced to that of control, with 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 to the control animals demonstrating that the β-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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping