Sites of insulin and glucagon metabolism in the rabbit nephron

Uptake and degradation of peptide hormones have been demonstrated in proximal convoluted tubules (PCT), but the contribution of other regions of the nephron to renal hormone metabolism is unknown. In the present study we used micromethods to determine for the first time the degradation of radiolabeled insulin and glucagon by each segment of the rabbit nephron and examined some characteristics of this process in proximal convoluted and cortical collecting tubules (CCT). Degradation of insulin (8-10 fmol . cm-1 . h-1) and glucagon (13-15 fmol . cm-1 . h-1) was maximal in proximal convoluted and straight tubules, but occurred to a substantial degree (approximately 25-30% of PCT) in all other segments of the nephron except the thin descending limb. In PCT degradation of both hormones was maximal at physiological pH, and competition studies suggested that it is brought about by both specific and nonspecific proteases. Most of the degrading activity (insulin, 86%; glucagon, 73%) was in the cytosol or could be eluted off the cell membrane or organelles. In the CCT, a representative segment of the distal nephron, the characteristics of insulin degradation were similar to those observed in the PCT, whereas glucagon degradation appeared to be due chiefly to nonspecific proteases. In conclusion, the metabolism of insulin and glucagon by isolated rabbit tubules occurs chiefly in the proximal convoluted and straight tubules, but up to one-third of the degrading capacity of the proximal nephron is also present in distal nephron segments.(ABSTRACT TRUNCATED AT 250 WORDS)