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Abstract: PO0728

Renal Mass Reduction Enhances the Blood Glucose Response to Exogenous Insulin in Rats

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Mannon, Elinor, Augusta University, Augusta, Georgia, United States
  • O'Connor, Paul, Augusta University, Augusta, Georgia, United States
Background

The effect of chronic kidney disease (CKD) on responses to exogenous insulin are complex and may vary depending on the level of underlying insulin resistance. The kidneys play an important role in the catabolism of insulin, and progression of CKD in patients with diabetes mellitus is often associated with reducing insulin needs. Conversely, impairments in insulin sensitivity are observed in CKD patients absent diabetes, indicating that CKD itself may drive insulin resistance.

Methods

In order to clarify the roles of CKD and underlying insulin resistance on the response to exogenous insulin, in the current study we investigated the effect of graded renal mass reduction on the blood glucose response to insulin in healthy Sprague Dawley (SD) and insulin resistant Zucker obese rats. Male SD (12 wks) and Zucker obese (10 wks) rats underwent either sham (n=6 SD, 3 Zucker), 2/3 nephrectomy (n=7 SD; Nx), or 5/6 Nx (n=8 SD, 4 Zucker). Rats recovered for 4 weeks, then underwent insulin tolerance testing (ITT; 0.75 U/kg i.v.).

Results

There was a graded response in the blood glucose curves for SD rats (PLevelofNx<0.0001; Fig 1A) with sham rats having the smallest blood glucose response to insulin, and 5/6 Nx rats having the greatest response to insulin. Similarly, the blood glucose response to insulin was about 5x greater for Zucker 5/6 Nx rats than for shams (PLevelofNx=0.0019; Fig 1B). There were no significant differences in plasma insulin levels during the ITT between Nx and sham SD rats, while sham Zucker rats had greater plasma insulin levels than Nx rats (PLevelofNx=0.0001).

Conclusion

These data indicate that renal mass reduction increases the response to exogenous insulin independent of the level of underlying insulin resistance, and that this is not mediated by an increased half-life of circulating insulin. Further investigation into the factors that contribute to greater insulin responses in CKD may identify novel targets for the treatment of insulin resistance.

Figure 1.

Funding

  • Other NIH Support