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)...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-07-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.921125/full |
| _version_ | 1811291936401653760 |
|---|---|
| author | Sakura Kiyobayashi Takaaki Murakami Norio Harada Hiroyuki Fujimoto Yuki Murata Naotaka Fujita Keita Hamamatsu Eri Ikeguchi-Ogura Tomonobu Hatoko Xuejing Lu Shunsuke Yamane Nobuya Inagaki |
| author_facet | Sakura Kiyobayashi Takaaki Murakami Norio Harada Hiroyuki Fujimoto Yuki Murata Naotaka Fujita Keita Hamamatsu Eri Ikeguchi-Ogura Tomonobu Hatoko Xuejing Lu Shunsuke Yamane Nobuya Inagaki |
| author_sort | Sakura Kiyobayashi |
| collection | DOAJ |
| 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 (111In)-labeled exendin-4 derivative ([Lys12(111In-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. 111In-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, 111In-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, 111In-exendin-4 SPECT/CT can be useful for evaluating increasing BCM and the role of GIP in BCM changes under HFD conditions. |
| first_indexed | 2024-04-13T04:36:53Z |
| format | Article |
| id | doaj.art-56eb90921da74ff78c9ad91627258319 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T04:36:53Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-56eb90921da74ff78c9ad916272583192022-12-22T03:02:08ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-07-011310.3389/fendo.2022.921125921125Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat DietSakura Kiyobayashi0Takaaki Murakami1Norio Harada2Hiroyuki Fujimoto3Yuki Murata4Naotaka Fujita5Keita Hamamatsu6Eri Ikeguchi-Ogura7Tomonobu Hatoko8Xuejing Lu9Shunsuke Yamane10Nobuya Inagaki11Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanRadioisotope Research Center, Agency of Health, Safety and Environment, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, JapanPancreatic 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 (111In)-labeled exendin-4 derivative ([Lys12(111In-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. 111In-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, 111In-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, 111In-exendin-4 SPECT/CT can be useful for evaluating increasing BCM and the role of GIP in BCM changes under HFD conditions.https://www.frontiersin.org/articles/10.3389/fendo.2022.921125/fullbeta cell massGIPexendinSPECThigh-fat diet |
| spellingShingle | Sakura Kiyobayashi Takaaki Murakami Norio Harada Hiroyuki Fujimoto Yuki Murata Naotaka Fujita Keita Hamamatsu Eri Ikeguchi-Ogura Tomonobu Hatoko Xuejing Lu Shunsuke Yamane Nobuya Inagaki Noninvasive Evaluation of GIP Effects on β-Cell Mass Under High-Fat Diet Frontiers in Endocrinology beta cell mass GIP exendin SPECT 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 | beta cell mass GIP exendin SPECT high-fat diet |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.921125/full |
| work_keys_str_mv | AT sakurakiyobayashi noninvasiveevaluationofgipeffectsonbcellmassunderhighfatdiet AT takaakimurakami noninvasiveevaluationofgipeffectsonbcellmassunderhighfatdiet AT norioharada noninvasiveevaluationofgipeffectsonbcellmassunderhighfatdiet AT hiroyukifujimoto noninvasiveevaluationofgipeffectsonbcellmassunderhighfatdiet AT yukimurata noninvasiveevaluationofgipeffectsonbcellmassunderhighfatdiet AT naotakafujita noninvasiveevaluationofgipeffectsonbcellmassunderhighfatdiet AT keitahamamatsu noninvasiveevaluationofgipeffectsonbcellmassunderhighfatdiet AT eriikeguchiogura noninvasiveevaluationofgipeffectsonbcellmassunderhighfatdiet AT tomonobuhatoko noninvasiveevaluationofgipeffectsonbcellmassunderhighfatdiet AT xuejinglu noninvasiveevaluationofgipeffectsonbcellmassunderhighfatdiet AT shunsukeyamane noninvasiveevaluationofgipeffectsonbcellmassunderhighfatdiet AT nobuyainagaki noninvasiveevaluationofgipeffectsonbcellmassunderhighfatdiet |