Chronic Renal Artery Insulin Infusion Decreases 24 hr/day Renal Blood Flow in Diabetic Rats

Abstract

The renal effects of type 1 diabetes, e.g. natriuresis and vasodilation, are ascribed directly to the hyperglycemia. We reported that 6 days of diabetes (~ 400 mg/dl) in dogs did not cause sustained natriuresis if plasma insulin was not allowed to decrease below normal. This suggested that the decrease in insulin and loss of its sodium retaining influence, rather than hyperglycemia, was responsible for sustained natriuresis in type 1 diabetes. This study tested the role of the decrease in insulin in mediating the renal blood flow (RBF) response to diabetes. Rats were instrumented with a chronic catheter in the left renal artery, inserted via a puncture in the aorta at the origination of the renal artery. The right kidney was removed, and a Transonic flow probe was placed on the left renal artery. Artery and vein catheters were implanted. The flow probe cable and catheters were exteriorized through a button in the scapular region and rats were placed in metabolic cages. They were connected to a Dragonfly commutator and Instech dual-channel hydraulic swivel mounted in series for continuous, 24 hr/day intravenous (IV) and intrarenal (IR) infusion while measuring RBF continuously, 24 hr/day. In 5 rats, RBF averaged 10.8±1.5 ml/min during baseline and averaged 11.0±0.7 ml/min during 1-4 days of diabetes (STZ, 40 mg/kg). Insulin then was added to the IR saline vehicle at a dose of 0.3 mU/kg/min, which we have reported did not spill over systemically in rats. The next four days of IR insulin infusion yielded decreasing RBF values of 10.9±1.3, 10.2±1.1, 7.9±1.2, and 7.8±1.0 ml/min. RBF did not recover when IR insulin was stopped, so 2 Control rats underwent 7 days of diabetes without IR insulin. Baseline RBF averaged 7.8 ml/min, and over the next 7 days averaged: 8.4, 12.0, 11.9, 10.9, 10.2, 10.6, and 10.7 ml/min. The RI insulin infusion also was tested in one additional rat that was not diabetic. There was no change in RBF or blood glucose over 4 days of infusion. These results suggest a chronic renal vasoconstrictor influence of insulin under diabetic conditions. We hypothesize this suggests that the decrease in insulin may contribute directly to the renal vasodilation that occurs in type 1 diabetes.