Insulin Metabolism in Chronic Uremia and in the Anephric State: Effect of the Dialytic Treatment1

Increased Clearance and Degradation of [3H]Insulin in Streptozotocin Diabetic Rats

“…Despite decreased blood glucose and increased plasma insulin, the disappearance of [3H]insulin from the plasma should not have been affected to any significant extent, provided that the insulin-removal mechanisms remained unsaturated over the range of insulin variations induced. We think that this is most likely the case because of reports that disappearance of 125I-insulin under basal conditions and during glucose infusion was the same (25) and the immunoreactive insulin curves obtained after infusing large amounts of either unlabeled or labeled hormone (15,(23)(24)(25) were essentially the same, apart from a scale factor. Finally, the results in the present studies show that changes in IDV for [3H]insulin occur following presaturation of the receptor compartment with native insulin (Table III) and that labeled material can be displaced from the receptor compartment of unlabeled insulin (Fig.…”

“…Blood samples (0.1 ml) were taken at times 1, 2,3, 5,6,7,8,10,15,20,25,30,35,40,45,50,55, and 60 min after injection. Total "4C-radioactivity and the concentration of intact [3H]insulin were then determined, the two isotopes being detected simultaneously in the scintillation counter.…”

Pathogenesis of Endocrine Abnormalities in Uremia*

“…Indeed, the levels of many polypeptide hormones are either increased or respond abnormally to suppressive or stimulatory maneuvers in renal failure, making this hypothesis rather attractive. Several lines of evidence indicate, however, that this is certainly not the only mechanism involved; the deranged metabolic environment of uremia per se may also interfere with the extrarenal degradation of certain hormones (7)(8)(9), or with the feedback controls that regulate their synthesis or secretion (10,11). In addition, inferring a direct cause and effect relationship between increased immunoassayable hormone levels and certain endocrine abnormalities may be erroneous, not only because the hormonal effect on target organs may be altered (12)(13)(14)(15), but also because in uremia the circulating immunoreactive hormone may be heterogeneous and include components without (or with uncertain) biological activity (16)(17)(18).…”

Metabolism of Polypeptide Hormones by the Normal Kidney and in Uremia

“…The mechanism of carbohydrate intolerance in uremia is not agreed upon, but the most com monly invoked explanation is that it is due to peripheral resistance to the action of insulin [9], On the other hand, impaired metabolism of insulin results in decreased insulin require ments in patients with diabetic nephropathy as their renal failure progresses. The decreased metabolic clearance of insulin in uremia is due mainly to the decrease in functioning renal mass, although 'toxic depression of insulin degradation' may be a contributing factor [24].…”