Sitagliptin and Roux-en-Y gastric bypass modulate insulin secretion via regulation of intra-islet peptide tyrosine tyrosine (PYY)

Diabetes, Obesity and Metabolism | September 13, 2017

Guida C, et al. - In this study, researchers aimed to notice these gaps and their impacts on glucose-stimulated insulin secretion (GSIS). They have also evaluated alterations in pancreatic peptide tyrosine tyrosine (PYY) in diabetes and following Roux-en-Y gastric bypass (RYGB). The results of this study displayed that local regulation of pancreatic PYY, rather than GLP-1, by DPP-IV inhibition or RYGB can directly modulate the insulin secretory response to glucose, indicating a novel role of pancreatic PYY in diabetes and weight-loss surgery.

Methods

  • Researchers applied immunohistochemistry and gene expression analysis to evaluate PYY, NPYRs and DPP-IV expression in human islets. DPP-IV activity inhibition was achieved by sitagliptin.
  • They applied secretion studies to test PYY and sitagliptin effects on insulin release, and the involvement of GLP-1.
  • They further used radioimmunoassays to measure hormone content in islets.

Results

  • It was noted that PYY and DPP-IV localized in different cell types in islets while NPYRs expression was confined to the beta-cells.
  • They observed that chronic PYY application enhanced GSIS diabetic human islets.
  • It was noted that DPP-IV inhibition by sitagliptin potentiated GSIS; this was mediated by locally-produced PYY, and not GLP-1.
  • The data indicated that pancreatic PYY was markedly reduced in diabetes. RYGB strongly increased islet PYY content, but did not lead to full restoration of pancreatic GLP-1 levels.

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