Maldi-TOF analysis of portal sera of pancreatic cancer patients: identification of diabetogenic and antidiabetogenic peptides

Background: Pancreatic cancer (PC) associated diabetes mellitus (DM) might be consequent to the diabetogenic effects of tumour products, possibly acting via nitric oxide (NO). Our aim were: (1) to verify whether PC associated DM determines an increased hepatic NO and (2) using MALDI-TOF analysis, to evaluate the peptide composition of PC cell conditioned media (CM) and of portal sera from patients with PC with (n = 7) or without (n = 4) DM. Methods: In liver tissue homogenates of 23 patients with PC (n = 17) or chronic pancreatitis (n = 6) GAPDH mRNA and activity, glucose, lactate, nitrite and nitrate were assayed. MALDI-TOF analysis was performed in three PC cell lines CM, and in portal sera from patients with PC. Results: Higher GAPDH mRNA and nitrite were found in patients with than in patients without DM. In PC cell CM, only 9 among a total of 75 fragments identified, were tumour specific. One hundred seventy-three fragments were identified in the portal sera of patients: one was positively and six fragments were negatively correlated with DM. Conclusions: Unlike liver GAPDH, NO appears to be involved in PC associated DM. In portal sera, the absence, rather than the presence, of specific fragments, appears to be correlated with the development of DM.