Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese, type-2 diabetes patients: a maladaptive response
Glucose-dependent insulinotropic polypeptide (GIP) beyond its insulinotropic effects may regulate postprandial lipid metabolism. Whereas the insulinotropic action of GIP is known to be impaired in type 2 diabetes mellitus (T2DM), its adipogenic effect is unknown. We hypothesized that GIP is anabolic...
| Autores: | , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2017 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/175938 |
| Acceso en línea: | https://hdl.handle.net/2445/175938 |
| Access Level: | acceso abierto |
| Palabra clave: | Diabetis Teixit adipós Diabetes Adipose tissues |
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Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese, type-2 diabetes patients: a maladaptive responseThondam, Sravan K.Daousi, ChristinaWIlding, John P.Holst, Jens J.Ameen, Gulizar IssaYang, ChenjingWhitmore, CatherineMora Fayos, SílviaCuthbertson, Daniel J.DiabetisTeixit adipósDiabetesAdipose tissuesGlucose-dependent insulinotropic polypeptide (GIP) beyond its insulinotropic effects may regulate postprandial lipid metabolism. Whereas the insulinotropic action of GIP is known to be impaired in type 2 diabetes mellitus (T2DM), its adipogenic effect is unknown. We hypothesized that GIP is anabolic in human subcutaneous adipose tissue (SAT) promoting triacylglycerol (TAG) deposition through reesterification of nonesterified fatty acids (NEFA), and this effect may differ according to obesity status or glucose tolerance. Twenty-three subjects categorized into four groups, normoglycemic lean (n = 6), normoglycemic obese (n = 6), obese with impaired glucose regulation (IGR; n = 6), and obese T2DM (n = 5), participated in a double-blind, randomized, crossover study involving a hyperglycemic clamp with a 240-min GIP infusion (2 pmol·kg−1·min−1) or normal saline. Insulin, NEFA, SAT-TAG content, and gene expression of key lipogenic enzymes were determined before and immediately after GIP/saline infusions. GIP lowered NEFA concentrations in the obese T2DM group despite diminished insulinotropic activity (mean NEFA AUC0-4 h ± SE, 41,992 ± 9,843 µmol·l−1·min−1 vs. 71,468 ± 13,605 with placebo, P = 0.039, 95% CI: 0.31-0.95). Additionally, GIP increased SAT-TAG in obese T2DM (1.78 ± 0.4 vs 0.86 ± 0.1-fold with placebo, P = 0.043, 95% CI: 0.1-1.8). Such effect with GIP was not observed in other three groups despite greater insulinotropic activity. Reduction in NEFA concentration with GIP correlated with adipose tissue insulin resistance for all subjects (Pearson, r = 0.56, P = 0.005). There were no significant gene expression changes in key SAT lipid metabolism enzymes. In conclusion, GIP appears to promote fat accretion and thus may exacerbate obesity and insulin resistance in T2DM.American Physiological Society2021202120172021info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion10 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/175938Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1152/ajpendo.00347.2016American Journal of Physiology-Endocrinology and Metabolism, 2017, vol. 312, p. E224-E233https://doi.org/10.1152/ajpendo.00347.2016(c) American Physiological Society, 2017info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1759382026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese, type-2 diabetes patients: a maladaptive response |
| title |
Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese, type-2 diabetes patients: a maladaptive response |
| spellingShingle |
Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese, type-2 diabetes patients: a maladaptive response Thondam, Sravan K. Diabetis Teixit adipós Diabetes Adipose tissues |
| title_short |
Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese, type-2 diabetes patients: a maladaptive response |
| title_full |
Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese, type-2 diabetes patients: a maladaptive response |
| title_fullStr |
Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese, type-2 diabetes patients: a maladaptive response |
| title_full_unstemmed |
Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese, type-2 diabetes patients: a maladaptive response |
| title_sort |
Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese, type-2 diabetes patients: a maladaptive response |
| dc.creator.none.fl_str_mv |
Thondam, Sravan K. Daousi, Christina WIlding, John P. Holst, Jens J. Ameen, Gulizar Issa Yang, Chenjing Whitmore, Catherine Mora Fayos, Sílvia Cuthbertson, Daniel J. |
| author |
Thondam, Sravan K. |
| author_facet |
Thondam, Sravan K. Daousi, Christina WIlding, John P. Holst, Jens J. Ameen, Gulizar Issa Yang, Chenjing Whitmore, Catherine Mora Fayos, Sílvia Cuthbertson, Daniel J. |
| author_role |
author |
| author2 |
Daousi, Christina WIlding, John P. Holst, Jens J. Ameen, Gulizar Issa Yang, Chenjing Whitmore, Catherine Mora Fayos, Sílvia Cuthbertson, Daniel J. |
| author2_role |
author author author author author author author author |
| dc.subject.none.fl_str_mv |
Diabetis Teixit adipós Diabetes Adipose tissues |
| topic |
Diabetis Teixit adipós Diabetes Adipose tissues |
| description |
Glucose-dependent insulinotropic polypeptide (GIP) beyond its insulinotropic effects may regulate postprandial lipid metabolism. Whereas the insulinotropic action of GIP is known to be impaired in type 2 diabetes mellitus (T2DM), its adipogenic effect is unknown. We hypothesized that GIP is anabolic in human subcutaneous adipose tissue (SAT) promoting triacylglycerol (TAG) deposition through reesterification of nonesterified fatty acids (NEFA), and this effect may differ according to obesity status or glucose tolerance. Twenty-three subjects categorized into four groups, normoglycemic lean (n = 6), normoglycemic obese (n = 6), obese with impaired glucose regulation (IGR; n = 6), and obese T2DM (n = 5), participated in a double-blind, randomized, crossover study involving a hyperglycemic clamp with a 240-min GIP infusion (2 pmol·kg−1·min−1) or normal saline. Insulin, NEFA, SAT-TAG content, and gene expression of key lipogenic enzymes were determined before and immediately after GIP/saline infusions. GIP lowered NEFA concentrations in the obese T2DM group despite diminished insulinotropic activity (mean NEFA AUC0-4 h ± SE, 41,992 ± 9,843 µmol·l−1·min−1 vs. 71,468 ± 13,605 with placebo, P = 0.039, 95% CI: 0.31-0.95). Additionally, GIP increased SAT-TAG in obese T2DM (1.78 ± 0.4 vs 0.86 ± 0.1-fold with placebo, P = 0.043, 95% CI: 0.1-1.8). Such effect with GIP was not observed in other three groups despite greater insulinotropic activity. Reduction in NEFA concentration with GIP correlated with adipose tissue insulin resistance for all subjects (Pearson, r = 0.56, P = 0.005). There were no significant gene expression changes in key SAT lipid metabolism enzymes. In conclusion, GIP appears to promote fat accretion and thus may exacerbate obesity and insulin resistance in T2DM. |
| publishDate |
2017 |
| dc.date.none.fl_str_mv |
2017 2021 2021 2021 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
| format |
article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/175938 |
| url |
https://hdl.handle.net/2445/175938 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Versió postprint del document publicat a: https://doi.org/10.1152/ajpendo.00347.2016 American Journal of Physiology-Endocrinology and Metabolism, 2017, vol. 312, p. E224-E233 https://doi.org/10.1152/ajpendo.00347.2016 |
| dc.rights.none.fl_str_mv |
(c) American Physiological Society, 2017 info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
(c) American Physiological Society, 2017 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
10 p. application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
American Physiological Society |
| publisher.none.fl_str_mv |
American Physiological Society |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Bioquímica i Biomedicina Molecular) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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