Sitagliptin and Roux-en-Y gastric bypass modulate insulin secretion via regulation of intra-islet PYY
The gut hormone peptide tyrosine tyrosine (PYY) is critical for maintaining islet integrity and restoring islet function following Roux-en-Y gastric bypass (RYGB). The expression of PYY and its receptors (NPYRs) in islets has been documented but not fully characterized. Modulation of islet PYY by th...
| Main Authors: | , , , , , , , , , |
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| 格式: | Journal article |
| 語言: | English |
| 出版: |
John Wiley & Sons Ltd
2017
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| _version_ | 1826303415581409280 |
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| author | Guida, C McCulloch, L Godazgar, M Stephen, S Baker, C Basco, D Dong, J Chen, D Clark, A Ramracheya, R |
| author_facet | Guida, C McCulloch, L Godazgar, M Stephen, S Baker, C Basco, D Dong, J Chen, D Clark, A Ramracheya, R |
| author_sort | Guida, C |
| collection | OXFORD |
| description | The gut hormone peptide tyrosine tyrosine (PYY) is critical for maintaining islet integrity and restoring islet function following Roux-en-Y gastric bypass (RYGB). The expression of PYY and its receptors (NPYRs) in islets has been documented but not fully characterized. Modulation of islet PYY by the proteolytic enzyme DPP-IV has not been investigated and the impact of DPP-IV inhibition on islet PYY function remains unexplored. Here we have addressed these gaps and their effects on glucose-stimulated insulin secretion (GSIS). We have also investigated changes in pancreatic PYY in diabetes and following RYGB.Immunohistochemistry and gene expression analysis were used to assess PYY, NPYRs and DPP-IV expression in rodent and human islets. DPP-IV activity inhibition was achieved by sitagliptin. Secretion studies were used to test PYY and sitagliptin effects on insulin release, and the involvement of GLP-1. Radioimmunoassays were used to measure hormone content in islets.PYY and DPP-IV localized in different cell types in islets while NPYRs expression was confined to the beta-cells. Chronic PYY application enhanced GSIS in rodent and diabetic human islets. DPP-IV inhibition by sitagliptin potentiated GSIS; this was mediated by locally-produced PYY, and not GLP-1. 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.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. |
| first_indexed | 2024-03-07T06:02:20Z |
| format | Journal article |
| id | oxford-uuid:eca48f8a-c07d-46d3-a93b-442d6c5426e4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:02:20Z |
| publishDate | 2017 |
| publisher | John Wiley & Sons Ltd |
| record_format | dspace |
| spelling | oxford-uuid:eca48f8a-c07d-46d3-a93b-442d6c5426e42022-03-27T11:19:00ZSitagliptin and Roux-en-Y gastric bypass modulate insulin secretion via regulation of intra-islet PYYJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:eca48f8a-c07d-46d3-a93b-442d6c5426e4EnglishSymplectic Elements at OxfordJohn Wiley & Sons Ltd2017Guida, CMcCulloch, LGodazgar, MStephen, SBaker, CBasco, DDong, JChen, DClark, ARamracheya, RThe gut hormone peptide tyrosine tyrosine (PYY) is critical for maintaining islet integrity and restoring islet function following Roux-en-Y gastric bypass (RYGB). The expression of PYY and its receptors (NPYRs) in islets has been documented but not fully characterized. Modulation of islet PYY by the proteolytic enzyme DPP-IV has not been investigated and the impact of DPP-IV inhibition on islet PYY function remains unexplored. Here we have addressed these gaps and their effects on glucose-stimulated insulin secretion (GSIS). We have also investigated changes in pancreatic PYY in diabetes and following RYGB.Immunohistochemistry and gene expression analysis were used to assess PYY, NPYRs and DPP-IV expression in rodent and human islets. DPP-IV activity inhibition was achieved by sitagliptin. Secretion studies were used to test PYY and sitagliptin effects on insulin release, and the involvement of GLP-1. Radioimmunoassays were used to measure hormone content in islets.PYY and DPP-IV localized in different cell types in islets while NPYRs expression was confined to the beta-cells. Chronic PYY application enhanced GSIS in rodent and diabetic human islets. DPP-IV inhibition by sitagliptin potentiated GSIS; this was mediated by locally-produced PYY, and not GLP-1. 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.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. |
| spellingShingle | Guida, C McCulloch, L Godazgar, M Stephen, S Baker, C Basco, D Dong, J Chen, D Clark, A Ramracheya, R Sitagliptin and Roux-en-Y gastric bypass modulate insulin secretion via regulation of intra-islet PYY |
| title | Sitagliptin and Roux-en-Y gastric bypass modulate insulin secretion via regulation of intra-islet PYY |
| title_full | Sitagliptin and Roux-en-Y gastric bypass modulate insulin secretion via regulation of intra-islet PYY |
| title_fullStr | Sitagliptin and Roux-en-Y gastric bypass modulate insulin secretion via regulation of intra-islet PYY |
| title_full_unstemmed | Sitagliptin and Roux-en-Y gastric bypass modulate insulin secretion via regulation of intra-islet PYY |
| title_short | Sitagliptin and Roux-en-Y gastric bypass modulate insulin secretion via regulation of intra-islet PYY |
| title_sort | sitagliptin and roux en y gastric bypass modulate insulin secretion via regulation of intra islet pyy |
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