GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis.
Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that potentiates glucose-stimulated insulin secretion during a meal. Since GIP has also been shown to exert β-cell prosurvival and adipocyte lipogenic effects in rodents, both GIP receptor agonists and antagonists have...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3388996?pdf=render |
| _version_ | 1811221768450342912 |
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| author | Su-Jin Kim Cuilan Nian Subashini Karunakaran Susanne M Clee Carlos M Isales Christopher H S McIntosh |
| author_facet | Su-Jin Kim Cuilan Nian Subashini Karunakaran Susanne M Clee Carlos M Isales Christopher H S McIntosh |
| author_sort | Su-Jin Kim |
| collection | DOAJ |
| description | Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that potentiates glucose-stimulated insulin secretion during a meal. Since GIP has also been shown to exert β-cell prosurvival and adipocyte lipogenic effects in rodents, both GIP receptor agonists and antagonists have been considered as potential therapeutics in type 2 diabetes (T2DM). In the present study, we tested the hypothesis that chronically elevating GIP levels in a transgenic (Tg) mouse model would increase adipose tissue expansion and exert beneficial effects on glucose homeostasis. In contrast, although GIP Tg mice demonstrated enhanced β-cell function, resulting in improved glucose tolerance and insulin sensitivity, they exhibited reduced diet-induced obesity. Adipose tissue macrophage infiltration and hepatic steatosis were both greatly reduced, and a number of genes involved in lipid metabolism/inflammatory signaling pathways were found to be down-regulated. Reduced adiposity in GIP Tg mice was associated with decreased energy intake, involving overexpression of hypothalamic GIP. Together, these studies suggest that, in the context of over-nutrition, transgenic GIP overexpression has the potential to improve hepatic and adipocyte function as well as glucose homeostasis. |
| first_indexed | 2024-04-12T08:06:07Z |
| format | Article |
| id | doaj.art-d81c14c65d904b4e959668416981da14 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T08:06:07Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d81c14c65d904b4e959668416981da142022-12-22T03:41:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4015610.1371/journal.pone.0040156GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis.Su-Jin KimCuilan NianSubashini KarunakaranSusanne M CleeCarlos M IsalesChristopher H S McIntoshGlucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that potentiates glucose-stimulated insulin secretion during a meal. Since GIP has also been shown to exert β-cell prosurvival and adipocyte lipogenic effects in rodents, both GIP receptor agonists and antagonists have been considered as potential therapeutics in type 2 diabetes (T2DM). In the present study, we tested the hypothesis that chronically elevating GIP levels in a transgenic (Tg) mouse model would increase adipose tissue expansion and exert beneficial effects on glucose homeostasis. In contrast, although GIP Tg mice demonstrated enhanced β-cell function, resulting in improved glucose tolerance and insulin sensitivity, they exhibited reduced diet-induced obesity. Adipose tissue macrophage infiltration and hepatic steatosis were both greatly reduced, and a number of genes involved in lipid metabolism/inflammatory signaling pathways were found to be down-regulated. Reduced adiposity in GIP Tg mice was associated with decreased energy intake, involving overexpression of hypothalamic GIP. Together, these studies suggest that, in the context of over-nutrition, transgenic GIP overexpression has the potential to improve hepatic and adipocyte function as well as glucose homeostasis.http://europepmc.org/articles/PMC3388996?pdf=render |
| spellingShingle | Su-Jin Kim Cuilan Nian Subashini Karunakaran Susanne M Clee Carlos M Isales Christopher H S McIntosh GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis. PLoS ONE |
| title | GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis. |
| title_full | GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis. |
| title_fullStr | GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis. |
| title_full_unstemmed | GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis. |
| title_short | GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis. |
| title_sort | gip overexpressing mice demonstrate reduced diet induced obesity and steatosis and improved glucose homeostasis |
| url | http://europepmc.org/articles/PMC3388996?pdf=render |
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