Physiological and pathophysiological actions of insulin in the liver
The liver plays an important role in the control of glucose homeostasis. When insulin levels are low, such as in the fasting state, gluconeogenesis and glycogenolysis are stimulated to maintain the blood glucose levels. Conversely, in the presence of increased insulin levels, such as after a meal, s...
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The Japan Endocrine Society
2025-02-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/72/2/72_EJ24-0192/_html/-char/en |
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| author | Naoto Kubota Tetsuya Kubota Takashi Kadowaki |
| author_facet | Naoto Kubota Tetsuya Kubota Takashi Kadowaki |
| author_sort | Naoto Kubota |
| collection | DOAJ |
| description | The liver plays an important role in the control of glucose homeostasis. When insulin levels are low, such as in the fasting state, gluconeogenesis and glycogenolysis are stimulated to maintain the blood glucose levels. Conversely, in the presence of increased insulin levels, such as after a meal, synthesis of glycogen and lipid occurs to maintain the blood glucose levels within normal range. Insulin receptor signaling regulates glycogenesis, gluconeogenesis and lipogenesis through downstream pathways such as the insulin receptor substrate (IRS)-phosphoinositide 3 (PI3) kinase-Akt pathway. IRS-1 and IRS-2 are abundantly expressed in the liver and are thought to be responsible for transmitting the insulin signal from the insulin receptor to the intracellular effectors involved in the regulation of glucose and lipid homeostasis. Impaired insulin receptor signaling can cause hepatic insulin resistance and lead to type 2 diabetes. In the present study, we focus on a concept called “selective insulin resistance,” which has received increasing attention recently: the frequent coexistence of hyperglycemia and hepatic steatosis in people with type 2 diabetes and obesity suggests that it is possible for the insulin signaling regulating gluconeogenesis to be impaired even while that regulating lipogenesis is preserved, suggestive of selective insulin resistance. In this review, we review the progress in research on the insulin actions and insulin signaling in the liver. |
| format | Article |
| id | doaj-art-cb2384297334481880387f70c0cc8c7e |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-cb2384297334481880387f70c0cc8c7e2025-02-03T01:08:32ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402025-02-0172214915910.1507/endocrj.EJ24-0192endocrjPhysiological and pathophysiological actions of insulin in the liverNaoto Kubota0Tetsuya Kubota1Takashi Kadowaki2Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, JapanDivision of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Tokyo 103-0002, JapanToranomon Hospital, Tokyo 105-8470, JapanThe liver plays an important role in the control of glucose homeostasis. When insulin levels are low, such as in the fasting state, gluconeogenesis and glycogenolysis are stimulated to maintain the blood glucose levels. Conversely, in the presence of increased insulin levels, such as after a meal, synthesis of glycogen and lipid occurs to maintain the blood glucose levels within normal range. Insulin receptor signaling regulates glycogenesis, gluconeogenesis and lipogenesis through downstream pathways such as the insulin receptor substrate (IRS)-phosphoinositide 3 (PI3) kinase-Akt pathway. IRS-1 and IRS-2 are abundantly expressed in the liver and are thought to be responsible for transmitting the insulin signal from the insulin receptor to the intracellular effectors involved in the regulation of glucose and lipid homeostasis. Impaired insulin receptor signaling can cause hepatic insulin resistance and lead to type 2 diabetes. In the present study, we focus on a concept called “selective insulin resistance,” which has received increasing attention recently: the frequent coexistence of hyperglycemia and hepatic steatosis in people with type 2 diabetes and obesity suggests that it is possible for the insulin signaling regulating gluconeogenesis to be impaired even while that regulating lipogenesis is preserved, suggestive of selective insulin resistance. In this review, we review the progress in research on the insulin actions and insulin signaling in the liver.https://www.jstage.jst.go.jp/article/endocrj/72/2/72_EJ24-0192/_html/-char/eninsulin receptor signalinginsulin resistanceselective insulin resistance |
| spellingShingle | Naoto Kubota Tetsuya Kubota Takashi Kadowaki Physiological and pathophysiological actions of insulin in the liver Endocrine Journal insulin receptor signaling insulin resistance selective insulin resistance |
| title | Physiological and pathophysiological actions of insulin in the liver |
| title_full | Physiological and pathophysiological actions of insulin in the liver |
| title_fullStr | Physiological and pathophysiological actions of insulin in the liver |
| title_full_unstemmed | Physiological and pathophysiological actions of insulin in the liver |
| title_short | Physiological and pathophysiological actions of insulin in the liver |
| title_sort | physiological and pathophysiological actions of insulin in the liver |
| topic | insulin receptor signaling insulin resistance selective insulin resistance |
| url | https://www.jstage.jst.go.jp/article/endocrj/72/2/72_EJ24-0192/_html/-char/en |
| work_keys_str_mv | AT naotokubota physiologicalandpathophysiologicalactionsofinsulinintheliver AT tetsuyakubota physiologicalandpathophysiologicalactionsofinsulinintheliver AT takashikadowaki physiologicalandpathophysiologicalactionsofinsulinintheliver |