Endoplasmic reticulum stress in the adipose tissue and monocyte chemoattractant protein‐1 are involved in tacrolimus‐induced diabetes mellitus
Abstract Tacrolimus is an independent risk factor for new‐onset diabetes after transplantation (NODAT). This study aimed to identify the mechanisms underlying tacrolimus‐induced NODAT. About 80 kidney‐transplant patients receiving tacrolimus were divided into NODAT and non‐NODAT groups after 1 year....
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| Format: | Article |
| Language: | English |
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Wiley
2023-06-01
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| Series: | Pharmacology Research & Perspectives |
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| Online Access: | https://doi.org/10.1002/prp2.1081 |
| _version_ | 1797800906468622336 |
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| author | Xiaoxia Sun Hongyang Wang Jingwei Chi Kui Che Yangang Wang |
| author_facet | Xiaoxia Sun Hongyang Wang Jingwei Chi Kui Che Yangang Wang |
| author_sort | Xiaoxia Sun |
| collection | DOAJ |
| description | Abstract Tacrolimus is an independent risk factor for new‐onset diabetes after transplantation (NODAT). This study aimed to identify the mechanisms underlying tacrolimus‐induced NODAT. About 80 kidney‐transplant patients receiving tacrolimus were divided into NODAT and non‐NODAT groups after 1 year. Binary logistic regression was used to identify risk factors for NODAT. Insulin resistance indices were estimated using the homeostasis model assessment. The blood levels of 13 adipocytokines were measured 1 week after transplantation. A tacrolimus‐induced diabetes mouse model was used to reveal the underlying mechanisms. The cumulative NODAT incidence was 12.7% at 1 year (median, 6 months; range, 3–12 months). Tacrolimus trough levels ≥10 ng/mL during the first 3 months (odds ratio: 2.54, p = .012) were related to NODAT. Insulin resistance indices were higher in NODAT patients than in non‐NODAT patients at 3, 6, and 12 months. Monocyte chemoattractant protein (MCP)‐1 was overexpressed in blood in NODAT patients. In the animal experiments, postprandial blood glucose and insulin levels, insulin pathway protein levels in adipose tissue, MCP‐1 expression in blood and adipose tissue, and number of macrophages in adipose tissue were markedly higher in tacrolimus‐treated mice than in control mice, and these increases were dose‐dependent. The expression of endoplasmic reticulum (ER) stress proteins in adipose tissue was increased in a tacrolimus dose‐dependent manner. In conclusion, tacrolimus‐induced insulin resistance. Tacrolimus trough levels ≥10 ng/mL during the first 3 postoperative months were an independent risk factor for NODAT. ER stress and MCP‐1 underlie tacrolimus‐induced diabetes. |
| first_indexed | 2024-03-13T04:42:17Z |
| format | Article |
| id | doaj.art-50ed7d4206be457baca1df921b4ea992 |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-03-13T04:42:17Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-50ed7d4206be457baca1df921b4ea9922023-06-19T04:55:55ZengWileyPharmacology Research & Perspectives2052-17072023-06-01113n/an/a10.1002/prp2.1081Endoplasmic reticulum stress in the adipose tissue and monocyte chemoattractant protein‐1 are involved in tacrolimus‐induced diabetes mellitusXiaoxia Sun0Hongyang Wang1Jingwei Chi2Kui Che3Yangang Wang4Department of Endocrinology the Affiliated Hospital of Qingdao University Qingdao ChinaDepartment of Kidney Transplantation the Affiliated Hospital of Qingdao University Qingdao ChinaDepartment of Endocrinology Laboratory the Affiliated Hospital of Qingdao University Qingdao ChinaDepartment of Endocrinology Laboratory the Affiliated Hospital of Qingdao University Qingdao ChinaDepartment of Endocrinology the Affiliated Hospital of Qingdao University Qingdao ChinaAbstract Tacrolimus is an independent risk factor for new‐onset diabetes after transplantation (NODAT). This study aimed to identify the mechanisms underlying tacrolimus‐induced NODAT. About 80 kidney‐transplant patients receiving tacrolimus were divided into NODAT and non‐NODAT groups after 1 year. Binary logistic regression was used to identify risk factors for NODAT. Insulin resistance indices were estimated using the homeostasis model assessment. The blood levels of 13 adipocytokines were measured 1 week after transplantation. A tacrolimus‐induced diabetes mouse model was used to reveal the underlying mechanisms. The cumulative NODAT incidence was 12.7% at 1 year (median, 6 months; range, 3–12 months). Tacrolimus trough levels ≥10 ng/mL during the first 3 months (odds ratio: 2.54, p = .012) were related to NODAT. Insulin resistance indices were higher in NODAT patients than in non‐NODAT patients at 3, 6, and 12 months. Monocyte chemoattractant protein (MCP)‐1 was overexpressed in blood in NODAT patients. In the animal experiments, postprandial blood glucose and insulin levels, insulin pathway protein levels in adipose tissue, MCP‐1 expression in blood and adipose tissue, and number of macrophages in adipose tissue were markedly higher in tacrolimus‐treated mice than in control mice, and these increases were dose‐dependent. The expression of endoplasmic reticulum (ER) stress proteins in adipose tissue was increased in a tacrolimus dose‐dependent manner. In conclusion, tacrolimus‐induced insulin resistance. Tacrolimus trough levels ≥10 ng/mL during the first 3 postoperative months were an independent risk factor for NODAT. ER stress and MCP‐1 underlie tacrolimus‐induced diabetes.https://doi.org/10.1002/prp2.1081diabetes mellitusendoplasmic reticulum stressmacrophage accumulationMCP‐1tacrolimus |
| spellingShingle | Xiaoxia Sun Hongyang Wang Jingwei Chi Kui Che Yangang Wang Endoplasmic reticulum stress in the adipose tissue and monocyte chemoattractant protein‐1 are involved in tacrolimus‐induced diabetes mellitus Pharmacology Research & Perspectives diabetes mellitus endoplasmic reticulum stress macrophage accumulation MCP‐1 tacrolimus |
| title | Endoplasmic reticulum stress in the adipose tissue and monocyte chemoattractant protein‐1 are involved in tacrolimus‐induced diabetes mellitus |
| title_full | Endoplasmic reticulum stress in the adipose tissue and monocyte chemoattractant protein‐1 are involved in tacrolimus‐induced diabetes mellitus |
| title_fullStr | Endoplasmic reticulum stress in the adipose tissue and monocyte chemoattractant protein‐1 are involved in tacrolimus‐induced diabetes mellitus |
| title_full_unstemmed | Endoplasmic reticulum stress in the adipose tissue and monocyte chemoattractant protein‐1 are involved in tacrolimus‐induced diabetes mellitus |
| title_short | Endoplasmic reticulum stress in the adipose tissue and monocyte chemoattractant protein‐1 are involved in tacrolimus‐induced diabetes mellitus |
| title_sort | endoplasmic reticulum stress in the adipose tissue and monocyte chemoattractant protein 1 are involved in tacrolimus induced diabetes mellitus |
| topic | diabetes mellitus endoplasmic reticulum stress macrophage accumulation MCP‐1 tacrolimus |
| url | https://doi.org/10.1002/prp2.1081 |
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