Glucose metabolic alterations in isolated and perfused rat hepatocytes induced by pancreatic cancer conditioned medium: A low molecular weight factorpossibly involved

A serious insulin resistance characterizes pancreatic cancer-associated dia betes mellitus. Elsewhere, we demonstrated that MIA PaCa2 cultured cells se crete a soluble factor responsible for reduced glucose tolerance induced in SCID mice. The intracellular mechanism of insulin resistance was investiga ted in isolated and perfused rat hepatocytes incubated with MIA PaCa2 condi tioned medium. Lactate production was reduced compared to hepatocytes incub ated with control medium while 1,2-DAG; was increased and PKC was activated in the hepatocytes incubated with MIA PaCa2 conditioned medium. This behav ior was not reproduced treating the hepatocytes with the growth factors EGF , interleukin I beta, interleukin-6, and TGF-beta 1. In an attempt to make a biochemical identification of the hypothesized tumor associated-diabetoge nic factors we observed a low molecular weight protein in the conditioned m edium, absent in the nonconditioned one, that may be responsible for the de scribed behaviors. (C) 1999 Academic Press.