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Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet

Pancreatic β-cell mass (BCM) has an importance in the pathophysiology of diabetes mellitus. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging has emerged as a promising tool for BCM evaluation. While glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP)...

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Autores principales: Kiyobayashi, Sakura, Murakami, Takaaki, Harada, Norio, Fujimoto, Hiroyuki, Murata, Yuki, Fujita, Naotaka, Hamamatsu, Keita, Ikeguchi-Ogura, Eri, Hatoko, Tomonobu, Lu, Xuejing, Yamane, Shunsuke, Inagaki, Nobuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326491/
https://www.ncbi.nlm.nih.gov/pubmed/35909510
http://dx.doi.org/10.3389/fendo.2022.921125
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author Kiyobayashi, Sakura
Murakami, Takaaki
Harada, Norio
Fujimoto, Hiroyuki
Murata, Yuki
Fujita, Naotaka
Hamamatsu, Keita
Ikeguchi-Ogura, Eri
Hatoko, Tomonobu
Lu, Xuejing
Yamane, Shunsuke
Inagaki, Nobuya
author_facet Kiyobayashi, Sakura
Murakami, Takaaki
Harada, Norio
Fujimoto, Hiroyuki
Murata, Yuki
Fujita, Naotaka
Hamamatsu, Keita
Ikeguchi-Ogura, Eri
Hatoko, Tomonobu
Lu, Xuejing
Yamane, Shunsuke
Inagaki, Nobuya
author_sort Kiyobayashi, Sakura
collection PubMed
description Pancreatic β-cell mass (BCM) has an importance in the pathophysiology of diabetes mellitus. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging has emerged as a promising tool for BCM evaluation. While glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP) is known to be involved in high-fat diet (HFD)-induced obesity, the effect of GIP on BCM is still controversial. In this study, we investigated indium 111 ((111)In)-labeled exendin-4 derivative ([Lys(12)((111)In-BnDTPA-Ahx)]exendin-4) single-photon emission computed tomography/computed tomography (SPECT/CT) as a tool for evaluation of longitudinal BCM changes in HFD-induced obese mice, at the same time we also investigated the effects of GIP on BCM in response to HFD using GIP-knockout (GIP(-/-)) mice. (111)In-exendin-4 SPECT/CT was able to distinguish control-fat diet (CFD)-fed mice from HFD-fed mice and the pancreatic uptake values replicated the BCM measured by conventional histological methods. Furthermore, BCM expansions in HFD-fed mice were demonstrated by time-course changes of the pancreatic uptake values. Additionally, (111)In-exendin-4 SPECT/CT demonstrated the distinct changes in BCM between HFD-fed GIP(-/-) (GIP(-/-)+HFD) and wild-type (WT+HFD) mice; the pancreatic uptake values of GIP(-/-)+HFD mice became significantly lower than those of WT+HFD mice. The different changes in the pancreatic uptake values between the two groups preceded those in fat accumulation and insulin resistance. Taken together with the finding of increased β-cell apoptosis in GIP(-/-)+HFD mice compared with WT+HFD mice, these data indicated that GIP has preferable effects on BCM under HFD. Therefore, (111)In-exendin-4 SPECT/CT can be useful for evaluating increasing BCM and the role of GIP in BCM changes under HFD conditions.
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spelling pubmed-93264912022-07-28 Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet Kiyobayashi, Sakura Murakami, Takaaki Harada, Norio Fujimoto, Hiroyuki Murata, Yuki Fujita, Naotaka Hamamatsu, Keita Ikeguchi-Ogura, Eri Hatoko, Tomonobu Lu, Xuejing Yamane, Shunsuke Inagaki, Nobuya Front Endocrinol (Lausanne) Endocrinology Pancreatic β-cell mass (BCM) has an importance in the pathophysiology of diabetes mellitus. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging has emerged as a promising tool for BCM evaluation. While glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP) is known to be involved in high-fat diet (HFD)-induced obesity, the effect of GIP on BCM is still controversial. In this study, we investigated indium 111 ((111)In)-labeled exendin-4 derivative ([Lys(12)((111)In-BnDTPA-Ahx)]exendin-4) single-photon emission computed tomography/computed tomography (SPECT/CT) as a tool for evaluation of longitudinal BCM changes in HFD-induced obese mice, at the same time we also investigated the effects of GIP on BCM in response to HFD using GIP-knockout (GIP(-/-)) mice. (111)In-exendin-4 SPECT/CT was able to distinguish control-fat diet (CFD)-fed mice from HFD-fed mice and the pancreatic uptake values replicated the BCM measured by conventional histological methods. Furthermore, BCM expansions in HFD-fed mice were demonstrated by time-course changes of the pancreatic uptake values. Additionally, (111)In-exendin-4 SPECT/CT demonstrated the distinct changes in BCM between HFD-fed GIP(-/-) (GIP(-/-)+HFD) and wild-type (WT+HFD) mice; the pancreatic uptake values of GIP(-/-)+HFD mice became significantly lower than those of WT+HFD mice. The different changes in the pancreatic uptake values between the two groups preceded those in fat accumulation and insulin resistance. Taken together with the finding of increased β-cell apoptosis in GIP(-/-)+HFD mice compared with WT+HFD mice, these data indicated that GIP has preferable effects on BCM under HFD. Therefore, (111)In-exendin-4 SPECT/CT can be useful for evaluating increasing BCM and the role of GIP in BCM changes under HFD conditions. Frontiers Media S.A. 2022-07-12 /pmc/articles/PMC9326491/ /pubmed/35909510 http://dx.doi.org/10.3389/fendo.2022.921125 Text en Copyright © 2022 Kiyobayashi, Murakami, Harada, Fujimoto, Murata, Fujita, Hamamatsu, Ikeguchi-Ogura, Hatoko, Lu, Yamane and Inagaki https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Kiyobayashi, Sakura
Murakami, Takaaki
Harada, Norio
Fujimoto, Hiroyuki
Murata, Yuki
Fujita, Naotaka
Hamamatsu, Keita
Ikeguchi-Ogura, Eri
Hatoko, Tomonobu
Lu, Xuejing
Yamane, Shunsuke
Inagaki, Nobuya
Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet
title Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet
title_full Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet
title_fullStr Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet
title_full_unstemmed Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet
title_short Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet
title_sort noninvasive evaluation of gip effects on β-cell mass under high-fat diet
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326491/
https://www.ncbi.nlm.nih.gov/pubmed/35909510
http://dx.doi.org/10.3389/fendo.2022.921125
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