The kidneys are the most important extrahepatic site of insulin breakdown and play a significant role in regulating the systemic insulin level in normal subjects. In man, a renal arteriovenous insulin concentration difference of about 30% has been measured, and since ‘insulin clearance’ values are less than the glomerular filtration rates, insulin is probably removed from blood by a combination of filtration and tubular secretion. In normal subjects a constant fraction of circulating insulin is removed by the kidney. This fraction is independent of the arterial concentration but varies with creatinine clearance. Of the amount filtered, most is completely resorbed and degraded by the cells of the proximal convoluted tubules. These cells have a high insulinase content and recent evidence would point to the possible existence of a renal tubular transport mechanism for insulin. The amount of insulin excreted in the urine is small and does not exceed 2% of the filtered load. In diabetics the insulin requirements often decrease with progressive renal failure. Derangements in carbohydrate metabolism have been noted in patients with renal failure while ‘insulin clearance’ is elevated in uraemia, chronic and acute renal failure. In nephrotic syndrome there is no change in renal insulin excretion. In severe trauma, ‘insulin clearance’ is elevated in patients with normal renal function despite a relative hypoinsulinaemia for the prevailing degree of glycaemia.
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