Clinical, stage 3, type 1 diabetes (T1D) is the consequence of beta-cell destruction by an auto-immune process, assumed to be beta cell-specific, i. e., not affecting other cell types of the pancreas whether endocrine or exocrine. However, the exocrine pancreas is frequently also altered in the course of T1D both anatomically and functionally [[1], [2], [3]]. It is unknown whether alterations of the exocrine pancreas, which often appear late in the course of T1D, but are sometimes already present at diagnosis [4] reflecting a global pancreas dysfunction, also include the other endocrine cells of the islets of Langerhans, i. e. alpha (glucagon-secreting cells), delta (somatostatin-secreting cells), and pancreatic polypeptide (PP)-secreting cells. It is also unknown whether there is a common pathogenic process for the destruction of beta cells and alterations in structure and function of the exocrine pancreas or if different pathogenic mechanisms are in play [1]. Concerning the other endocrine cell types, glucagon secretion is also altered in T1D with increased fasting glucagon concentration but decreased response to hypoglycemia [[5], [6], [7]], associated with a modest alpha cell mass decrease that occurs late in the course of the disease [8].

The aim of the present study was to investigate whether endocrine failure can globally affect the function of the islets of Langerhans in T1D, especially when T1D is complicated by exocrine failure, or whether endocrine failure stays limited to beta cells even in patients with exocrine failure. Global pancreas dysfunction, involving both exocrine and whole endocrine pancreas, is the hallmark of the so-called diseases of the pancreas, type3c or pancreatogenic diabetes. This group of classification of diabetes [9] includes pancreatectomy, cystic fibrosis-related diabetes and diabetes complicating chronic pancreatitis (CP). Diabetes secondary to CP is characterized by global destruction of the pancreatic parenchyma, leading to both endocrine and exocrine insufficiencies. All the cell types of the islets of Langerhans are involved, including beta cells, but also alpha, delta, and PP-secreting cells) [10,11]. With the exception of insulin, PP is the only pancreas-specific hormone, although rare neuroendocrine tumors of the rectum have been found to express PP [12] and can thus be used as a marker of global endocrine failure at difference with glucagon that can also be secreted by enteroendocrine L cells as described after total pancreatectomy [13]. PP cells are found at the periphery of the islets, especially in the “PP-rich lobe” of the uncinate process, but also scattered throughout the exocrine parenchyma and can also be found in the pancreatic duct epithelium [14]. PP is secreted during meals and acts as a peripheral anorexigenic signal by inducing satiety via the activation of Y4 receptors of the neuropeptide Y family in the hypothalamus and it also slows gastric emptying [15]. We therefore investigated PP secretion as a global marker of pancreatic endocrine function in patients with T1D, either without or with exocrine failure. Patients with chronic pancreas were used as control subjects.