Physiological hyperinsulinemia caused by acute hyperglycemia minimizes renal sodium loss by direct action on kidneys

Debra L. Irsik, Michael W. Brands

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


This study used acute, renal artery insulin infusion in conscious rats to test the hypothesis that hyperinsulinemia attenuates glucose-induced natriuresis by a direct renal mechanism. We reported previously that hyperinsulinemia was required to prevent ad libitum eating or an acute glucose bolus from causing excessive renal sodium loss. Rats were instrumented with renal artery, aortic, and femoral vein catheters and Data Sciences International blood pressure telemeters and were housed in metabolic cages. Insulin was clamped chronically at normal levels in two groups [vehicle infused (irV) and insulin infused (irI)] by administering streptozotocin and then infusing insulin intravenously 24 h/day to maintain normal blood glucose. Bolus glucose administration was used as a meal substitute to produce hyperglycemia that was not different between groups, and urinary sodium excretion (UNaV) was measured over the next 4 h. In the irV and control (C) rats, vehicle was infused in the renal artery during that period, whereas insulin was infused in the renal artery of the irI rats. Plasma insulin increased significantly in C rats but not in either of the clamped groups. UNaV in the irV rats, which could not increase circulating insulin levels, was approximately threefold greater than in C rats, similar to our previous report. However, allowing the kidney of irI rats to experience hyperinsulinemia via the renal artery insulin infusion completely prevented this, with no blood pressure differences. These data support our hypothesis that meal-induced increases in plasma insulin are a major component of normal sodium homeostasis, and that this occurs by direct action of insulin on the kidney.

Original languageEnglish (US)
Pages (from-to)R547-R552
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number3
StatePublished - Sep 2018


  • Hypertension
  • Insulin
  • Intrarenal
  • Kidney
  • Natriuresis
  • Postprandial

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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