Chronic Insulin‐clamp Causes Postprandial Diuresis in Sprague Dawley Rats

Abstract

Understanding the physiologic role of insulin in salt and volume homeostasis is important for interpreting its contribution to disease states such as diabetes or metabolic syndrome. This study tested the hypothesis that the rise in plasma insulin that occurs postprandially is required to minimize renal sodium (Na+) and volume losses. Rats were instrumented with chronic artery and vein catheters, housed in metabolic cages, and connected to Instech hydraulic swivels. Na+ intake was clamped chronically at normal by feeding Na+ deficient diet and infusing saline 24 hr/day. Measurements of 24 hr Na+ and volume excretions and 4‐ and 8‐hr postprandial Na+ and volume excretions were made under control conditions (CTL) and during insulin‐clamped conditions (I‐C) to prevent the postprandial insulin surge. The chronic I‐C was accomplished by administering STZ and subsequently infusing insulin 24 hr/day to clamp insulin at normal levels that maintained normal fasting blood glucose. Twenty‐four hr urine volume and Na+ excretion were greater in the I‐C vs. CTL rats (33±2 vs. 17±1 ml/day and 3.8±0.1 vs. 2.9±0.2 mmol/day, respectively; n=5–9; p<0.05) despite lower fasting blood glucose levels (93±9 vs. 129±5 mg/dl). Postprandial measurements were made after feeding a calorie‐dense gel to rats that had been fasted overnight. Postprandial urine volume was greater in I‐C rats after 4 hrs (5.5±1.6 vs. 2.7±0.3 ml, n=4–8; p<0.05) and 8 hrs (7.0 vs. 2.8 ml), and postprandial GFR was lower in the I‐C rats (1.8±0.4 vs. 2.2±0.4 ml/min), consistent with decreased tubular reabsorption. Postprandial blood glucose increased more in the I‐C rats (307±80 vs. 141±11 mg/dl, n=4–8; p<0.05). These data suggest that the postprandial surge in insulin is necessary to prevent renal salt and volume losses, because rats that were unable to increase insulin after a meal exhibited increased diuresis. Future studies will be needed to quantify the relative roles of insulin‐mediated glucose disposal vs. insulin‐mediated renal tubular Na+ reabsorption.Support or Funding InformationHL056259 and HL056259‐S1