Translocation of intestinal alkaline phosphatase in streptozotocin-induced diabetic rats

1. We determined the organ of origin and possible mechanism of translocation into the circulation of alkaline phosphatase (ALPase) in the diabetic rat. 2. Experimental diabetes was induced by injection of streptozotocin, resulting in a 8.2-fold elevation in serum ALPase activity. In this case, the major ALPase isozyme detected in serum was intestinal ALPase. 3. In in vitro experimental systems, ALPase was readily released from the duodenal plasma membrane by bacterial phosphatidylinositol-specific-phospholipase C (PI-PLase C) but little if any was released from the ileal membrane. 4. Serum and ileal ALPases were identical in terms of molecular size, whereas duodenal ALPase clearly differed from the serum enzyme. 5. Based on an investigation of the sugar moiety, more of the fraction having higher concanavalin A affinity was found in serum ALPase than with in the case of either of the intestinal ALPases. Serum and intestinal ALPases also differed slightly regarding isoelectric points. 6. Consequently, these data suggest that the serum ALPase of the diabetic rat is derived from ileal ALPase, and it is unlikely that the appearance of ALPase in the circulation is simply the result of solubilization by the action of PI-PLase C or phospholipase D.