Purpose: Proximal intestinal bypass (PIB), such as Billroth II or Roux-en-Y gastrojejunostomy after curative distal gastrectomy for gastric cancer induces beneficial effects on glycemic control in patients with type 2 diabetes. We aimed to characterize the long-term evolution of pancreatic beta cells and insulin signaling in target tissue after a PIB procedure. Methods: Zucker diabetic fatty rats were randomly assigned to the PIB, sham-operated PIB pair-fed, and ad libitum fed groups. Oral glucose tolerance (GT) and plasma insulin levels were measured periodically at 16 weeks postoperatively. Histomorphometric analyses were performed to evaluate changes in islet architectures and intranuclear pancreatic duodenal homeobox 1 (PDX1) expression in beta cells. Insulin signaling changes in visceral adipocytes were measured by the phosphorylated Akt/Akt ratio. Results: Contrary to the progressively deteriorating GT and plasma insulin levels in sham-operated animals, these were preserved in PIB animals (P < 0.01) at 16 weeks postoperatively. The proportion of the islets having asteroid-like expanding projection was higher in PIB animals than in sham-operated animals (P < 0.01). PIB animals had 3-fold wider fractional area of beta cells (P < 0.01) and 3-fold higher proportion of beta-cell nuclear PDX1 expression (P < 0.01) than sham-operated animals. PIB animals had significantly higher levels of Akt phosphorylation in the visceral adipocytes (P < 0.05). The PIB did not substantially affect weight and food intake postoperatively. Conclusion: The PIB preserved the plasma insulin levels and the wider beta-cell area over time and facilitated insulin signaling in the visceral fats. It could be considered as a possible reconstruction strategy for diabetic gastric cancer patients.
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