Insulin influence (used as an additive to dialysate) on the mitogenic-induced effect of the peritoneal effluent in...

Peritoneal effluent in CAPD patients is the result of the interaction between dialysate and patient through the peritoneal membrane. Among the factors transferred from the patient to dialysate are solutes capable of stimulating fibroblasts: Interleukin-I, Interferon-gamma, and other proteins. Insulin is a well known mitogenic coadjuvant able to act sinergistically with other mitogens in the stimulation of fibroblast proliferation under experimental conditions. Our objective has been to study the effect of insulin added to dialysate in vivo on the in vitro mitogen-induced capacity of the nocturnal peritoneal effluent in 8 diabetics. Two different samples were studied: basal and with in vivo added insulin with the patients' usual doses. A Swiss 3T3 line of mice fibroblasts was used for studies, adding 50 microliters of peritoneal effluent. To confirm in vivo potential mitogenic activity, we also added PDBu (Phorbol dibuturate), a well known mitogenic agent, to both samples. Furthermore, another growth factor, EGF (Epidermal growth factor), was also added to 5 other samples. Insulin addition to the CAPD bag transforms a non-mitogenic peritoneal effluent into a mitogenic one (mean: 4.4 times over basal). At the doses used in vivo there is no linear correlation between insulin dose and DNA synthesis (r: -0.28, NS). Both PDBu and EGF in vitro addition induced a remarkable increment in the mitogenic capacity of the peritoneal effluent. We conclude that insulin added to CAPD bags behaves as a remarkable mitogenic coadjuvant for mice fibroblasts. Consequently, its long-term and universal clinical use should be reconsidered.