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PYY-Dependent Restoration of Impaired Insulin and Glucagon Secretion in Type 2 Diabetes following Roux-En-Y Gastric Bypass Surgery

Roux-en-Y gastric bypass (RYGB) is a weight-reduction procedure resulting in rapid resolution of type 2 diabetes (T2D). The role of pancreatic islet function in this restoration of normoglycemia has not been fully elucidated. Using the diabetic Goto-Kakizaki (GK) rat model, we demonstrate that RYGB...

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Autores principales: Ramracheya, Reshma D., McCulloch, Laura J., Clark, Anne, Wiggins, David, Johannessen, Helene, Olsen, Magnus Kringstad, Cai, Xing, Zhao, Chun-Mei, Chen, Duan, Rorsman, Patrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063952/
https://www.ncbi.nlm.nih.gov/pubmed/27117413
http://dx.doi.org/10.1016/j.celrep.2016.03.091
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author Ramracheya, Reshma D.
McCulloch, Laura J.
Clark, Anne
Wiggins, David
Johannessen, Helene
Olsen, Magnus Kringstad
Cai, Xing
Zhao, Chun-Mei
Chen, Duan
Rorsman, Patrik
author_facet Ramracheya, Reshma D.
McCulloch, Laura J.
Clark, Anne
Wiggins, David
Johannessen, Helene
Olsen, Magnus Kringstad
Cai, Xing
Zhao, Chun-Mei
Chen, Duan
Rorsman, Patrik
author_sort Ramracheya, Reshma D.
collection PubMed
description Roux-en-Y gastric bypass (RYGB) is a weight-reduction procedure resulting in rapid resolution of type 2 diabetes (T2D). The role of pancreatic islet function in this restoration of normoglycemia has not been fully elucidated. Using the diabetic Goto-Kakizaki (GK) rat model, we demonstrate that RYGB restores normal glucose regulation of glucagon and insulin secretion and normalizes islet morphology. Culture of isolated islets with serum from RYGB animals mimicked these effects, implicating a humoral factor. These latter effects were reversed following neutralization of the gut hormone peptide tyrosine tyrosine (PYY) but persisted in the presence of a glucagon-like peptide-1 (GLP-1) receptor antagonist. The effects of RYGB on secretion were replicated by chronic exposure of diabetic rat islets to PYY in vitro. These findings indicate that the mechanism underlying T2D remission may be mediated by PYY and suggest that drugs promoting PYY release or action may restore pancreatic islet function in T2D.
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spelling pubmed-50639522016-10-18 PYY-Dependent Restoration of Impaired Insulin and Glucagon Secretion in Type 2 Diabetes following Roux-En-Y Gastric Bypass Surgery Ramracheya, Reshma D. McCulloch, Laura J. Clark, Anne Wiggins, David Johannessen, Helene Olsen, Magnus Kringstad Cai, Xing Zhao, Chun-Mei Chen, Duan Rorsman, Patrik Cell Rep Report Roux-en-Y gastric bypass (RYGB) is a weight-reduction procedure resulting in rapid resolution of type 2 diabetes (T2D). The role of pancreatic islet function in this restoration of normoglycemia has not been fully elucidated. Using the diabetic Goto-Kakizaki (GK) rat model, we demonstrate that RYGB restores normal glucose regulation of glucagon and insulin secretion and normalizes islet morphology. Culture of isolated islets with serum from RYGB animals mimicked these effects, implicating a humoral factor. These latter effects were reversed following neutralization of the gut hormone peptide tyrosine tyrosine (PYY) but persisted in the presence of a glucagon-like peptide-1 (GLP-1) receptor antagonist. The effects of RYGB on secretion were replicated by chronic exposure of diabetic rat islets to PYY in vitro. These findings indicate that the mechanism underlying T2D remission may be mediated by PYY and suggest that drugs promoting PYY release or action may restore pancreatic islet function in T2D. Cell Press 2016-04-21 /pmc/articles/PMC5063952/ /pubmed/27117413 http://dx.doi.org/10.1016/j.celrep.2016.03.091 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Report
Ramracheya, Reshma D.
McCulloch, Laura J.
Clark, Anne
Wiggins, David
Johannessen, Helene
Olsen, Magnus Kringstad
Cai, Xing
Zhao, Chun-Mei
Chen, Duan
Rorsman, Patrik
PYY-Dependent Restoration of Impaired Insulin and Glucagon Secretion in Type 2 Diabetes following Roux-En-Y Gastric Bypass Surgery
title PYY-Dependent Restoration of Impaired Insulin and Glucagon Secretion in Type 2 Diabetes following Roux-En-Y Gastric Bypass Surgery
title_full PYY-Dependent Restoration of Impaired Insulin and Glucagon Secretion in Type 2 Diabetes following Roux-En-Y Gastric Bypass Surgery
title_fullStr PYY-Dependent Restoration of Impaired Insulin and Glucagon Secretion in Type 2 Diabetes following Roux-En-Y Gastric Bypass Surgery
title_full_unstemmed PYY-Dependent Restoration of Impaired Insulin and Glucagon Secretion in Type 2 Diabetes following Roux-En-Y Gastric Bypass Surgery
title_short PYY-Dependent Restoration of Impaired Insulin and Glucagon Secretion in Type 2 Diabetes following Roux-En-Y Gastric Bypass Surgery
title_sort pyy-dependent restoration of impaired insulin and glucagon secretion in type 2 diabetes following roux-en-y gastric bypass surgery
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063952/
https://www.ncbi.nlm.nih.gov/pubmed/27117413
http://dx.doi.org/10.1016/j.celrep.2016.03.091
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