Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling
Under healthy conditions, pancreatic β-cells produce and secrete the insulin hormone in response to blood glucose levels. Under diabetic conditions, however, β-cells are compelled to continuously secrete larger amounts of insulin to reduce blood glucose levels, and thereby, the β-cell function is de...
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/24/9444 |
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| author | Hideaki Kaneto Atsushi Obata Tomohiko Kimura Masashi Shimoda Junpei Sanada Yoshiro Fushimi Naoto Katakami Takaaki Matsuoka Kohei Kaku |
| author_facet | Hideaki Kaneto Atsushi Obata Tomohiko Kimura Masashi Shimoda Junpei Sanada Yoshiro Fushimi Naoto Katakami Takaaki Matsuoka Kohei Kaku |
| author_sort | Hideaki Kaneto |
| collection | DOAJ |
| description | Under healthy conditions, pancreatic β-cells produce and secrete the insulin hormone in response to blood glucose levels. Under diabetic conditions, however, β-cells are compelled to continuously secrete larger amounts of insulin to reduce blood glucose levels, and thereby, the β-cell function is debilitated in the long run. In the diabetic state, expression levels of insulin gene transcription factors and incretin receptors are downregulated, which we think is closely associated with β-cell failure. These data also suggest that it would be better to use incretin-based drugs at an early stage of diabetes when incretin receptor expression is preserved. Indeed, it was shown that incretin-based drugs exerted more protective effects on β-cells at an early stage. Furthermore, it was shown recently that endothelial cell dysfunction was also associated with pancreatic β-cell dysfunction. After ablation of insulin signaling in endothelial cells, the β-cell function and mass were substantially reduced, which was also accompanied by reduced expression of insulin gene transcription factors and incretin receptors in β-cells. On the other hand, it has been drawing much attention that incretin plays a protective role against the development of atherosclerosis. Many basic and clinical data have underscored the importance of incretin in arteries. Furthermore, it was shown recently that incretin receptor expression was downregulated in arteries under diabetic conditions, which likely diminishes the protective effects of incretin against atherosclerosis. Furthermore, a series of large-scale clinical trials (SPAED-A, SPIKE, LEADER, SUSTAIN-6, REWIND, PIONEER trials) have shown that various incretin-related drugs have beneficial effects against atherosclerosis and subsequent cardiovascular events. These data strengthen the hypothesis that incretin plays an important role in the arteries of humans, as well as rodents. |
| first_indexed | 2024-03-10T14:08:43Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:08:43Z |
| publishDate | 2020-12-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-491b9f3f945e47c6a7e60609b67526922023-11-21T00:25:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124944410.3390/ijms21249444Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin SignalingHideaki Kaneto0Atsushi Obata1Tomohiko Kimura2Masashi Shimoda3Junpei Sanada4Yoshiro Fushimi5Naoto Katakami6Takaaki Matsuoka7Kohei Kaku8Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki 701-0192, JapanDepartment of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, JapanDepartment of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, JapanDepartment of General Internal Medicine 1, Kawasaki Medical School, Kurashiki 701-0192, JapanUnder healthy conditions, pancreatic β-cells produce and secrete the insulin hormone in response to blood glucose levels. Under diabetic conditions, however, β-cells are compelled to continuously secrete larger amounts of insulin to reduce blood glucose levels, and thereby, the β-cell function is debilitated in the long run. In the diabetic state, expression levels of insulin gene transcription factors and incretin receptors are downregulated, which we think is closely associated with β-cell failure. These data also suggest that it would be better to use incretin-based drugs at an early stage of diabetes when incretin receptor expression is preserved. Indeed, it was shown that incretin-based drugs exerted more protective effects on β-cells at an early stage. Furthermore, it was shown recently that endothelial cell dysfunction was also associated with pancreatic β-cell dysfunction. After ablation of insulin signaling in endothelial cells, the β-cell function and mass were substantially reduced, which was also accompanied by reduced expression of insulin gene transcription factors and incretin receptors in β-cells. On the other hand, it has been drawing much attention that incretin plays a protective role against the development of atherosclerosis. Many basic and clinical data have underscored the importance of incretin in arteries. Furthermore, it was shown recently that incretin receptor expression was downregulated in arteries under diabetic conditions, which likely diminishes the protective effects of incretin against atherosclerosis. Furthermore, a series of large-scale clinical trials (SPAED-A, SPIKE, LEADER, SUSTAIN-6, REWIND, PIONEER trials) have shown that various incretin-related drugs have beneficial effects against atherosclerosis and subsequent cardiovascular events. These data strengthen the hypothesis that incretin plays an important role in the arteries of humans, as well as rodents.https://www.mdpi.com/1422-0067/21/24/9444pancreatic β-cell dysfunctionatherosclerosisincretin signalinginsulin signaling |
| spellingShingle | Hideaki Kaneto Atsushi Obata Tomohiko Kimura Masashi Shimoda Junpei Sanada Yoshiro Fushimi Naoto Katakami Takaaki Matsuoka Kohei Kaku Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling International Journal of Molecular Sciences pancreatic β-cell dysfunction atherosclerosis incretin signaling insulin signaling |
| title | Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling |
| title_full | Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling |
| title_fullStr | Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling |
| title_full_unstemmed | Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling |
| title_short | Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling |
| title_sort | notable underlying mechanism for pancreatic β cell dysfunction and atherosclerosis pleiotropic roles of incretin and insulin signaling |
| topic | pancreatic β-cell dysfunction atherosclerosis incretin signaling insulin signaling |
| url | https://www.mdpi.com/1422-0067/21/24/9444 |
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