THE MECHANISM OF GLUCOSE EXCRETION BY THE KIDNEY IN DIABETIC DOGS

Abstract

Kidney function has long been explained by two rival concepts, the secretion theory and the filtration-reabsorption theory, both being based upon inferences and indirect arguments rather than upon direct observations. Since the splendid work of Richards and his collaborators (1), the study of renal function is no longer a matter of theoretical discussion but one of exact measurements and analysis. As a result of these investigations and those of Rehberg (2), Marshall (3), and Homer Smith (4), it has been shown that the formation of the urine results from glomerular filtration, tubular reabsorption, and from some secretory activities. The relative importance of these processes depends on the particular species of animals under consideration. In amphibians, the behavior of the glucose in the kidney is known in the minutest details. Direct observations and analysis of fluids collected from different levels of the nephrons in the frog and Necturus have shown that the concentration of glucose is the same in the glomerular fluid as in the plasma, and that glucose is reabsorbed by the proximal portion of the tubules. When a full dose of phlorizin is injected into a frog, the tubular cells fail to reabsorb the glucose and the latter is thus found in the bladder urine. Aglomerular fishes do not excrete glucose when the plasma glucose is raised to a very high level, nor after administration of phlorizin. These observations can be interpreted as follows: the glucose is not secreted, but reaches the nephron only by the process of glomerular filtration and is reabsorbed by the tubules. The action of phlorizin consists in blocking the tubular reabsorption of glucose. If these observations may be fully applied to mammals, all of the filtered glucose should appear in the bladder urine when reabsorption is wholly blocked by phlorizin. In order to verify this assumption, it is necessary to determine the volume of the glomerular filtrate accurately. In 1926, Rehberg (2) suggested that the creatinine clearance may be used to measure the volume of the glomerular filtrate. According to Smith, Rehberg's inference is not correct for man, the anthropoid apes, and the birds, but is correct for the dog. So, for the dog, we can calculate the amount of filtered glucose by multiplying the creatinine clearance (filtration) by the concentration of the glucose in the arterial plasma, as it may be assumed that the concentration of glucose in the glomerular filtrate is the same as that in the arterial plasma. It is now easy to determine whether after the administration of phlorizin the total amount of filtered glucose is excreted. Poulsson (5) has proven the soundness of that concept experimentally. When a large dose of phlorizin is injected into a dog, the concentration index of glucose may equal the concentration index of creatinine. This means that if the kidney excretes in one minute the creatinine present in 60 cc. of plasma, it excretes during the same period the glucose present in 60 cc. of plasma. These findings have been confirmed by Jolliffe, Shannon, and Smith (6), by White and Monaghan (7) and by Govaerts and Cambier (8). Therefore, one is led to infer that in the dog as well as in the frog glucose enters the nephron only by glomerular filtration. If, under normal conditions, no glucose is found in the bladder urine, it is because this substance is completely reabsorbed by the tubules. When the concentration of glucose is raised in the plasma, it increases to the same extent in the glomerular filtrate. Thus, the amount of glucose presented to the reabsorbing cells reaches such a height that the reabsorption ceases to be complete. Fisher and Shannon (quoted by Smith (4) page 112) have studied the excretion of glucose by the kidney of a normal dog. The glucose in the arterial plasma was maintained at a very high level by the constant intravenous infusion of a glucose-saline solution. The quantity of glucose reabsorbed by the tubules remained