Department of Medicine, First Faculty of Medicine and Central Military Hospital, Charles University, Prague, Czech Republic.
Pancreas. 2012 Jul;41(5):663-70. doi: 10.1097/MPA.0b013e31823b5827.
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.
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.
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.
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.
胰腺腺癌中的新发糖尿病是由于胰岛素抵抗和β细胞功能下降的共同作用。其与常见的 2 型糖尿病的区别是胰腺腺癌早期诊断的前提。人们对胰腺基质和表面蛋白酶的关注较少。
活化的成纤维细胞选择性地表达成纤维细胞激活蛋白α，它是广泛表达的二肽基肽酶 4 的结构同源物。综述了它们在胰腺发生中的作用。
两种酶的同源二聚体和异源二聚体均对具有倒数第二位脯氨酸或丙氨酸的肽和蛋白质具有高特异性。大多数葡萄糖稳态调节剂是这些酶的候选底物。截断底物的生物学活性降低或缺失。
表面蛋白酶与葡萄糖稳态调节剂的相互作用可以充分解释与胰腺腺癌相关的糖尿病的演变，并将其与常见的 2 型糖尿病区分开来。
