Exploring mechanisms of insulin action and strategies to treat diabetes
Insulin is a hormone that positively regulates anabolism and cell growth, whereas diabetes mellitus is a disease characterized by hyperglycemia associated with impaired insulin action. My colleagues and I have elucidated multifaceted insulin action in various tissues mainly by means of model mice. I...
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The Japan Endocrine Society
2024-07-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/71/7/71_EJ24-0003/_html/-char/en |
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| author | Takayoshi Sasako |
| author_facet | Takayoshi Sasako |
| author_sort | Takayoshi Sasako |
| collection | DOAJ |
| description | Insulin is a hormone that positively regulates anabolism and cell growth, whereas diabetes mellitus is a disease characterized by hyperglycemia associated with impaired insulin action. My colleagues and I have elucidated multifaceted insulin action in various tissues mainly by means of model mice. In the liver, insulin regulates endoplasmic reticulum (ER) stress response during feeding, whereas ER stress ‘response failure’ contributes to the development of steatohepatitis comorbid with diabetes. Not only the liver but also the proximal tubules of the kidney are important in the regulation of gluconeogenesis, and we revealed that insulin suppresses gluconeogenesis in accordance with absorbed glucose in the latter tissue. In skeletal muscle, another important insulin-targeted tissue, impaired insulin/IGF-1 signaling leads not only to sarcopenia, an aging-related disease of skeletal muscle, but also to osteopenia and shorter longevity. Aging is regulated by adipokines as well, and it should be considered that aging could be accelerated by ‘imbalanced adipokines’ in patients with a genetic background of progeria. Moreover, we reported the effects of intensive multifactorial intervention on diabetic vascular complications and mortality in patients with type 2 diabetes in a large-scale clinical trial, the J-DOIT3, and the results of subsequent sub-analyses of renal events and fracture events. Various approaches of research enable us of endocrinologists to elucidate the physiology of hormone signaling, the mechanisms underlying the development of endocrine diseases, and the appropriate treatment measures. These approaches also raise fundamental questions, but addressing them in an appropriate manner will surely contribute to the further development of endocrinology. |
| format | Article |
| id | doaj-art-a5a3e8c5e0c2478abb7049d1119973e6 |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-a5a3e8c5e0c2478abb7049d1119973e62025-01-22T05:12:18ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402024-07-0171765166010.1507/endocrj.EJ24-0003endocrjExploring mechanisms of insulin action and strategies to treat diabetesTakayoshi Sasako0Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, JapanInsulin is a hormone that positively regulates anabolism and cell growth, whereas diabetes mellitus is a disease characterized by hyperglycemia associated with impaired insulin action. My colleagues and I have elucidated multifaceted insulin action in various tissues mainly by means of model mice. In the liver, insulin regulates endoplasmic reticulum (ER) stress response during feeding, whereas ER stress ‘response failure’ contributes to the development of steatohepatitis comorbid with diabetes. Not only the liver but also the proximal tubules of the kidney are important in the regulation of gluconeogenesis, and we revealed that insulin suppresses gluconeogenesis in accordance with absorbed glucose in the latter tissue. In skeletal muscle, another important insulin-targeted tissue, impaired insulin/IGF-1 signaling leads not only to sarcopenia, an aging-related disease of skeletal muscle, but also to osteopenia and shorter longevity. Aging is regulated by adipokines as well, and it should be considered that aging could be accelerated by ‘imbalanced adipokines’ in patients with a genetic background of progeria. Moreover, we reported the effects of intensive multifactorial intervention on diabetic vascular complications and mortality in patients with type 2 diabetes in a large-scale clinical trial, the J-DOIT3, and the results of subsequent sub-analyses of renal events and fracture events. Various approaches of research enable us of endocrinologists to elucidate the physiology of hormone signaling, the mechanisms underlying the development of endocrine diseases, and the appropriate treatment measures. These approaches also raise fundamental questions, but addressing them in an appropriate manner will surely contribute to the further development of endocrinology.https://www.jstage.jst.go.jp/article/endocrj/71/7/71_EJ24-0003/_html/-char/eninsulindiabetic mellitusmouse modelcase reportclinical trial |
| spellingShingle | Takayoshi Sasako Exploring mechanisms of insulin action and strategies to treat diabetes Endocrine Journal insulin diabetic mellitus mouse model case report clinical trial |
| title | Exploring mechanisms of insulin action and strategies to treat diabetes |
| title_full | Exploring mechanisms of insulin action and strategies to treat diabetes |
| title_fullStr | Exploring mechanisms of insulin action and strategies to treat diabetes |
| title_full_unstemmed | Exploring mechanisms of insulin action and strategies to treat diabetes |
| title_short | Exploring mechanisms of insulin action and strategies to treat diabetes |
| title_sort | exploring mechanisms of insulin action and strategies to treat diabetes |
| topic | insulin diabetic mellitus mouse model case report clinical trial |
| url | https://www.jstage.jst.go.jp/article/endocrj/71/7/71_EJ24-0003/_html/-char/en |
| work_keys_str_mv | AT takayoshisasako exploringmechanismsofinsulinactionandstrategiestotreatdiabetes |