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The Fatty Acid Receptor GPR40 Plays a Role in Insulin Secretion In Vivo After High-Fat Feeding
OBJECTIVE—The G-protein–coupled receptor GPR40 is expressed in pancreatic β-cells and is activated by long-chain fatty acids. Gene deletion studies have shown that GPR40 mediates, at least in part, fatty acid–amplification of glucose-induced insulin secretion (GSIS) but is not implicated in GSIS its...
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Formato: | Texto |
Lenguaje: | English |
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American Diabetes Association
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518494/ https://www.ncbi.nlm.nih.gov/pubmed/18559658 http://dx.doi.org/10.2337/db08-0553 |
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author | Kebede, Melkam Alquier, Thierry Latour, Martin G. Semache, Meriem Tremblay, Caroline Poitout, Vincent |
author_facet | Kebede, Melkam Alquier, Thierry Latour, Martin G. Semache, Meriem Tremblay, Caroline Poitout, Vincent |
author_sort | Kebede, Melkam |
collection | PubMed |
description | OBJECTIVE—The G-protein–coupled receptor GPR40 is expressed in pancreatic β-cells and is activated by long-chain fatty acids. Gene deletion studies have shown that GPR40 mediates, at least in part, fatty acid–amplification of glucose-induced insulin secretion (GSIS) but is not implicated in GSIS itself. However, the role of GPR40 in the long-term effects of fatty acids on insulin secretion remains controversial. This study aimed to test the hypothesis that GPR40 plays a role in insulin secretion after high-fat feeding. RESEARCH DESIGN AND METHODS—GPR40 knockout (KO) mice on a C57BL/6 background and their wild-type (WT) littermates were fed a high-fat diet (HFD) for 11 weeks. Glucose tolerance, insulin tolerance, and insulin secretion in response to glucose and Intralipid were assessed during the course of the diet period. RESULTS—GPR40 KO mice had fasting hyperglycemia. They became as obese, glucose intolerant, and insulin resistant as their WT littermates given HFD and developed a similar degree of liver steatosis. Their fasting blood glucose levels increased earlier than those of control mice during the course of the HFD. The remarkable increase in insulin secretory responses to intravenous glucose and Intralipid seen in WT mice after HFD was of much lower magnitude in GPR40 KO mice. CONCLUSIONS—GPR40 plays a role not only in fatty acid modulation of insulin secretion, but also in GSIS after high-fat feeding. These observations raise doubts on the validity of a therapeutic approach based on GPR40 antagonism for the treatment of type 2 diabetes. |
format | Text |
id | pubmed-2518494 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-25184942009-09-01 The Fatty Acid Receptor GPR40 Plays a Role in Insulin Secretion In Vivo After High-Fat Feeding Kebede, Melkam Alquier, Thierry Latour, Martin G. Semache, Meriem Tremblay, Caroline Poitout, Vincent Diabetes Islet Studies OBJECTIVE—The G-protein–coupled receptor GPR40 is expressed in pancreatic β-cells and is activated by long-chain fatty acids. Gene deletion studies have shown that GPR40 mediates, at least in part, fatty acid–amplification of glucose-induced insulin secretion (GSIS) but is not implicated in GSIS itself. However, the role of GPR40 in the long-term effects of fatty acids on insulin secretion remains controversial. This study aimed to test the hypothesis that GPR40 plays a role in insulin secretion after high-fat feeding. RESEARCH DESIGN AND METHODS—GPR40 knockout (KO) mice on a C57BL/6 background and their wild-type (WT) littermates were fed a high-fat diet (HFD) for 11 weeks. Glucose tolerance, insulin tolerance, and insulin secretion in response to glucose and Intralipid were assessed during the course of the diet period. RESULTS—GPR40 KO mice had fasting hyperglycemia. They became as obese, glucose intolerant, and insulin resistant as their WT littermates given HFD and developed a similar degree of liver steatosis. Their fasting blood glucose levels increased earlier than those of control mice during the course of the HFD. The remarkable increase in insulin secretory responses to intravenous glucose and Intralipid seen in WT mice after HFD was of much lower magnitude in GPR40 KO mice. CONCLUSIONS—GPR40 plays a role not only in fatty acid modulation of insulin secretion, but also in GSIS after high-fat feeding. These observations raise doubts on the validity of a therapeutic approach based on GPR40 antagonism for the treatment of type 2 diabetes. American Diabetes Association 2008-09 /pmc/articles/PMC2518494/ /pubmed/18559658 http://dx.doi.org/10.2337/db08-0553 Text en Copyright © 2008, American Diabetes Association https://creativecommons.org/licenses/by-nc-nd/3.0/Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Islet Studies Kebede, Melkam Alquier, Thierry Latour, Martin G. Semache, Meriem Tremblay, Caroline Poitout, Vincent The Fatty Acid Receptor GPR40 Plays a Role in Insulin Secretion In Vivo After High-Fat Feeding |
title | The Fatty Acid Receptor GPR40 Plays a Role in Insulin Secretion In Vivo After High-Fat Feeding |
title_full | The Fatty Acid Receptor GPR40 Plays a Role in Insulin Secretion In Vivo After High-Fat Feeding |
title_fullStr | The Fatty Acid Receptor GPR40 Plays a Role in Insulin Secretion In Vivo After High-Fat Feeding |
title_full_unstemmed | The Fatty Acid Receptor GPR40 Plays a Role in Insulin Secretion In Vivo After High-Fat Feeding |
title_short | The Fatty Acid Receptor GPR40 Plays a Role in Insulin Secretion In Vivo After High-Fat Feeding |
title_sort | fatty acid receptor gpr40 plays a role in insulin secretion in vivo after high-fat feeding |
topic | Islet Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518494/ https://www.ncbi.nlm.nih.gov/pubmed/18559658 http://dx.doi.org/10.2337/db08-0553 |
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