Early diagnosis of pancreatic adenocarcinoma: role of stroma, surface proteases, and glucose-homeostatic agents.

Objectives: New-onset diabetes in pancreatic adenocarcinoma is due to a combination of insulin resistance and decreased β-cell function. Its differentiation from the common type 2 diabetes is the prerequisite for early diagnosis of pancreatic adenocarcinoma. Little attention has been paid to pancreatic stroma and surface proteases.

Methods: The activated fibroblasts selectively express fibroblast activation protein α, a structural homolog of the ubiquitously expressed dipeptidyl peptidase 4. Their role in pancreatic carcinogenesis is reviewed.

Results: Homodimers and heterodimers of both enzymes display high specificity for peptides and proteins with penultimate proline or alanine. Most glucose-homeostatic agents are candidate substrates of these enzymes. The biological activity of truncated substrates is decreased or absent.

Conclusions: The interactions of surface proteases with glucose-homeostatic agents may adequately explain the evolution of diabetes associated with pancreatic adenocarcinoma and differentiate it from the common type 2 diabetes.