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Pancreas. 2014 May;43(4):651-6. doi: 10.1097/MPA.0000000000000082.

Elevated pancreatic polypeptide levels in pancreatic neuroendocrine tumors and diabetes mellitus: causation or association?

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From the Departments of *Surgery, †Internal Medicine, and ‡Pathology, University of Iowa College of Medicine, Iowa City, IA.


Pancreatic neuroendocrine tumors (PNETs) that secrete primarily pancreatic polypeptide (PP) are rare and usually nonfunctional. There are approximately 2 dozen reports of PP-secreting PNETs, 3 of which have been associated with diabetes mellitus (DM). None suggest a mechanism for the association between PP-secreting PNETs and DM. We describe 5 patients with PP-producing tumors who were diagnosed with DM at the same time as their PNETs, review the literature on PP, and consider its role in the pathophysiology of DM. The cases discussed were extracted from our surgical neuroendocrine tumor database. We examined all patients with PP-predominant PNETs--both with DM (n = 5) and without (n = 8). The 5 patients with DM at the time of PNET diagnosis demonstrated improvement or resolution of their DM postoperatively. In the patients with PP-secreting PNETs but no diagnosis of DM preoperatively, 1 became hypoglycemic postoperatively, and 2 others developed postoperative DM. The 5 cases discussed in detail raise the question of whether the hypersecretion of PP in PNETs might be an important event leading to the development of DM. Although the literature does not provide a mechanism for this association, it may be related to the role of PP in hepatic glucose regulation.

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