Kidney Week

Abstract: PO0725

Metabolic Acidosis Does Not Impair Insulin Sensitivity in Rats with CKD

Session Information

• Diabetic Kidney Disease: Basic - II
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 601 Diabetic Kidney Disease: Basic

Authors

• Mannon, Elinor, Augusta University, Augusta, Georgia, United States

Elinor Mannon

• O'Connor, Paul, Augusta University, Augusta, Georgia, United States

Paul O'Connor,

Background

Insulin resistance is common in patients with chronic kidney disease (CKD) without diabetes, however, the factors driving this remain unclear. Metabolic acidosis has been implicated in the development of insulin resistance. The current study was designed to quantify the effect of changes in blood pH on insulin sensitivity using a rodent model of CKD.

Methods

We hypothesized that alkali or acid loading would promote varying levels of acid-base disturbances and consequently decreased insulin sensitivity in rats with graded renal mass reduction. Male Sprague Dawley rats (12 wks, SD) underwent either 2/3 nephrectomy (n=7; Nx) or 5/6 Nx (n=4). Rats recovered for 4 weeks, then underwent insulin tolerance testing (ITT; 0.75 U/kg i.v.) before and after alkali (2 weeks 0.1M NaHCO₃) and acid loading (1 week 0.1M NH₄Cl) in the drinking water. Male Zucker obese rats (10 wks) underwent 5/6 Nx (n=4) and were also given 4 weeks of recovery before being placed on 0.1M NH₄Cl for 4 days.

Results

In Nx SD rats, 0.1M NaHCO₃ did not produce metabolic alkalosis (Table 1) or reduce insulin sensitivity (P_Rx=0.67). 0.1M NH₄Cl in Nx SD rats produced a mild metabolic acidosis (Table 1). However, this did not alter the response to insulin (P_Rx=0.56). 0.1M NH₄Cl produced a severe metabolic acidosis in Zucker rats with 5/6 Nx (Table 1). Again however, this was not associated with an impaired insulin response. Rather, following NH₄Cl loading, Zucker rats had a greater response to insulin (P_Rx=0.01). Unexpectedly, we observed a negative relationship between the magnitude of change in blood glucose (inverse area under the curve) and plasma pH (r=-0.27, P=0.03) and plasma HCO₃^- (r=-0.33, P=0.0098) in remnant kidney rats.

Conclusion

These data demonstrate that metabolic acidosis does not impair insulin sensitivity in rats. Our data suggest that the direct effects of metabolic acidosis are unlikely to underlie significant impairments in insulin sensitivity in CKD.

Table 1.

Funding

• Other NIH Support