Islet Inflammation and Ductal Proliferation, a Link to Pancreattisin Type-2 Diabetes?
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ABSTRACT: Pancreatitis is more frequent in type 2 diabetes (T2DM) although the underlying cause is unknown. We tested the hypothesis that ongoing beta-cell stress and apoptosis in T2DM induces ductal tree proliferation, particularly the pancreatic duct gland (PDG) compartment, and thus potentially obstructs exocrine outflow. PDG replication was increased two-fold in human pancreas from individuals with T2DM (P<0.01), and was associated with increased pancreatic intraepithelial neoplasia (PanINs) (P<0.05), lesions associated with pancreatic inflammation and with the potential to obstruct pancreatic outflow. Increased PDG replication (p<0.05) in the prediabetic HIP rat model of T2DM was concordant with increased beta-cell stress but preceding metabolic derangement. Moreover, the most abundantly expressed chemokines released by the islets in response to beta-cell stress in T2DM, CXCL1, 4 and 10, induced proliferation in human pancreatic ductal epithelium (p<0.05). Also, the diabetes medications that are reported as potential modifiers for the risk of pancreatitis in T2DM modulated PDG proliferation accordingly. We conclude that chronic stimulation and proliferation of the PDG compartment of the pancreas in response to islet inflammation in T2DM is a novel mechanism that serves as a link to the increased risk for pancreatitis in T2DM and may potentially be modified by currently available diabetes therapy.
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE90779 | GEO | 2016/12/02
SECONDARY ACCESSION(S): PRJNA355882
REPOSITORIES: GEO
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