Feb 2, 2017

Phenotyping of adipose, liver, and skeletal muscle insulin resistance and response to pioglitazone in spontaneously obese rhesus monkeys

American Journal of Physiology. Endocrinology and Metabolism
Jin ShangDavid E Kelley

Abstract

Insulin resistance and diabetes can develop spontaneously with obesity and aging in rhesus monkeys, highly similar to the natural history of obesity, insulin resistance, and progression to type 2 diabetes in humans. The current studies in obese rhesus were undertaken to assess hepatic and adipose contributions to systemic insulin resistance-currently, a gap in our knowledge-and to benchmark the responses to pioglitazone (PIO). A two-step hyperinsulinemic-euglycemic clamp, with tracer-based glucose flux estimates, was used to measure insulin resistance, and in an intervention study was repeated following 6 wk of PIO treatment (3 mg/kg). Compared with lean healthy rhesus, obese rhesus has a 60% reduction of glucose utilization during a high insulin infusion and markedly impaired suppression of lipolysis, which was evident at both low and high insulin infusion. However, obese dysmetabolic rhesus manifests only mild hepatic insulin resistance. Six-week PIO treatment significantly improved skeletal muscle and adipose insulin resistance (by ~50%). These studies strengthen the concept that insulin resistance in obese rhesus closely resembles human insulin resistance and indicate the value of obese rhesus for appraising new insulin-sen...Continue Reading

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References

  • References1
  • Citations1

Citations

Mentioned in this Paper

Diabetes Mellitus, Non-Insulin-Dependent
Study
Insulin Sensitivity
Fat Pad
Insulin/Insulin Receptor Signaling Pathway
Pemoline
Hepatic
Soleus Muscle Structure
Insulin Resistance
Hyperinsulinemic Hypoglycemia, Familial, 1

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