Alterations in Pancreatic Islet Cell Function in Response to Small Bowel Resection.

Background - After massive small bowel resection (SBR), mice exhibit hepatic steatosis, impaired glucose metabolism without insulin resistance, and increased pancreatic islet area. We sought to determine the consequences of SBR on pancreatic b-cell morphology, proliferation, and expression of a key regulatory hormone, glucagon like peptide-1 (GLP-1). Methods - C57Bl/6 mice underwent 50% SBR or sham operation. At 10 weeks, pancreatic insulin content and secretion was measured by ELISA. Immunohistochemistry was performed to determine alterations in pancreatic a- and b-cells. Western blot analysis was used to measure GLP-1R expression and immunoassay was used to measure plasma insulin and GLP-1. Results - After SBR, we identified pancreatic islet hypertrophy and impaired glucose tolerance. The proportion of a- and b-cells was not grossly altered. Whole pancreas and pancreatic islet insulin content was not significantly different; however, SBR pancreas demonstrated decreased insulin secretion in both static incubation and islet perfusion experiments. The expression of pancreatic GLP-1R was decreased approximately 2-fold after SBR and serum GLP-1 levels were decreased. Administration of a GLP-1 agonist mitigated the metabolic derangements. Conclusion Following massive SBR, there is significant hypertrophy of pancreatic islet cells with morphologically intact a- and b-cells. Significantly reduced pancreatic insulin release in both static and dynamic conditions demonstrate perturbed intrinsic b-cell function. GLP-1 is a key mediator of this amplification pathway. Decreased expression of serum GLP-1 and pancreatic GLP-1R in face of no change in insulin content offer a novel pathway for enteropancreatic glucose regulation following SBR.