Renal mass reduction increases the response to exogenous insulin independent of acid-base status or plasma insulin levels in rats

Elinor C. Mannon, Christina L. Sartain, Trevin C. Wilkes, Jingping Sun, Aaron J. Polichnowski, Paul M. O'Connor

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Impairments in insulin sensitivity can occur in patients with chronic kidney disease (CKD). Correction of metabolic acidosis has been associated with improved insulin sensitivity in CKD, suggesting that metabolic acidosis may directly promote insulin resistance. Despite this, the effect of acid or alkali loading on insulin sensitivity in a rodent model of CKD (remnant kidney) has not been directly investigated. Such studies could better define the relationship between blood pH and insulin sensitivity. We hypothesized that in remnant kidney rats, acid or alkali loading would promote loss of pH homeostasis and consequently decrease insulin sensitivity. To test this hypothesis, we determined the impact of alkali (2 wk) or acid (5-7 days) loading on plasma electrolytes, acid-base balance, and insulin sensitivity in either sham control rats, 2/3 nephrectomized rats, or 5/6 nephrectomized rats. Rats with 5/6 nephrectomy had the greatest response to insulin followed by rats with 2/3 nephrectomy and sham control rats. We found that treatment with 0.1 M sodium bicarbonate solution in drinking water had no effect on insulin sensitivity. Acid loading with 0.1 M ammonium chloride resulted in significant reductions in pH and plasma bicarbonate. However, acidosis did not significantly impair insulin sensitivity. Similar effects were observed in Zucker obese rats with 5/6 nephrectomy. The effect of renal mass reduction on insulin sensitivity could not be explained by reduced insulin clearance or increased plasma insulin levels. We found that renal mass reduction alone increases sensitivity to exogenous insulin in rats and that this is not acutely reversed by the development of acidosis.

Original languageEnglish (US)
Pages (from-to)F494-F504
JournalAmerican Journal of Physiology - Renal Physiology
Issue number4
StatePublished - Sep 2021


  • Blood glucose
  • Chronic kidney disease
  • Insulin resistance
  • Metabolic acidosis
  • Zucker obese rat

ASJC Scopus subject areas

  • Physiology
  • Urology


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