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Hypothalamic AMP-Activated Protein Kinase Regulates Biphasic Insulin Secretion from Pancreatic β Cells during Fasting and in Type 2 Diabetes
Glucose-stimulated insulin secretion (GSIS) by pancreatic β cells is biphasic. However, the physiological significance of biphasic GSIS and its relationship to diabetes are not yet fully understood. This study demonstrated that impaired first-phase GSIS follows fasting, leading to increased blood gl...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264491/ https://www.ncbi.nlm.nih.gov/pubmed/28005533 http://dx.doi.org/10.1016/j.ebiom.2016.10.038 |
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author | Kume, Shinji Kondo, Motoyuki Maeda, Shiro Nishio, Yoshihiko Yanagimachi, Tsuyoshi Fujita, Yukihiro Haneda, Masakazu Kondo, Keiko Sekine, Akihiro Araki, Shin-ich Araki, Hisazumi Chin-Kanasaki, Masami Ugi, Satoshi Koya, Daisuke Kitahara, Sawako Maeda, Kiyosumi Kashiwagi, Atsunori Uzu, Takashi Maegawa, Hiroshi |
author_facet | Kume, Shinji Kondo, Motoyuki Maeda, Shiro Nishio, Yoshihiko Yanagimachi, Tsuyoshi Fujita, Yukihiro Haneda, Masakazu Kondo, Keiko Sekine, Akihiro Araki, Shin-ich Araki, Hisazumi Chin-Kanasaki, Masami Ugi, Satoshi Koya, Daisuke Kitahara, Sawako Maeda, Kiyosumi Kashiwagi, Atsunori Uzu, Takashi Maegawa, Hiroshi |
author_sort | Kume, Shinji |
collection | PubMed |
description | Glucose-stimulated insulin secretion (GSIS) by pancreatic β cells is biphasic. However, the physiological significance of biphasic GSIS and its relationship to diabetes are not yet fully understood. This study demonstrated that impaired first-phase GSIS follows fasting, leading to increased blood glucose levels and brain glucose distribution in humans. Animal experiments to determine a possible network between the brain and β cells revealed that fasting-dependent hyperactivation of AMP-activated protein kinase in the hypothalamus inhibited first-phase GSIS by stimulating the α-adrenergic pancreatic nerve. Furthermore, abnormal excitability of this brain-β cell neural axis was involved in diabetes-related impairment of first-phase GSIS in diabetic animals. Finally, pancreatic denervation improved first-phase GSIS and glucose tolerance and ameliorated severe diabetes by preventing β cell loss in diabetic animals. These results indicate that impaired first-phase GSIS is critical for brain distribution of dietary glucose after fasting. Furthermore, β cells in individuals with diabetes mistakenly sense that they are under conditions that mimic prolonged fasting. The present study provides additional insight into both β cell physiology and the pathogenesis of β cell dysfunction in type 2 diabetes. |
format | Online Article Text |
id | pubmed-5264491 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-52644912017-02-01 Hypothalamic AMP-Activated Protein Kinase Regulates Biphasic Insulin Secretion from Pancreatic β Cells during Fasting and in Type 2 Diabetes Kume, Shinji Kondo, Motoyuki Maeda, Shiro Nishio, Yoshihiko Yanagimachi, Tsuyoshi Fujita, Yukihiro Haneda, Masakazu Kondo, Keiko Sekine, Akihiro Araki, Shin-ich Araki, Hisazumi Chin-Kanasaki, Masami Ugi, Satoshi Koya, Daisuke Kitahara, Sawako Maeda, Kiyosumi Kashiwagi, Atsunori Uzu, Takashi Maegawa, Hiroshi EBioMedicine Research Paper Glucose-stimulated insulin secretion (GSIS) by pancreatic β cells is biphasic. However, the physiological significance of biphasic GSIS and its relationship to diabetes are not yet fully understood. This study demonstrated that impaired first-phase GSIS follows fasting, leading to increased blood glucose levels and brain glucose distribution in humans. Animal experiments to determine a possible network between the brain and β cells revealed that fasting-dependent hyperactivation of AMP-activated protein kinase in the hypothalamus inhibited first-phase GSIS by stimulating the α-adrenergic pancreatic nerve. Furthermore, abnormal excitability of this brain-β cell neural axis was involved in diabetes-related impairment of first-phase GSIS in diabetic animals. Finally, pancreatic denervation improved first-phase GSIS and glucose tolerance and ameliorated severe diabetes by preventing β cell loss in diabetic animals. These results indicate that impaired first-phase GSIS is critical for brain distribution of dietary glucose after fasting. Furthermore, β cells in individuals with diabetes mistakenly sense that they are under conditions that mimic prolonged fasting. The present study provides additional insight into both β cell physiology and the pathogenesis of β cell dysfunction in type 2 diabetes. Elsevier 2016-10-28 /pmc/articles/PMC5264491/ /pubmed/28005533 http://dx.doi.org/10.1016/j.ebiom.2016.10.038 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Kume, Shinji Kondo, Motoyuki Maeda, Shiro Nishio, Yoshihiko Yanagimachi, Tsuyoshi Fujita, Yukihiro Haneda, Masakazu Kondo, Keiko Sekine, Akihiro Araki, Shin-ich Araki, Hisazumi Chin-Kanasaki, Masami Ugi, Satoshi Koya, Daisuke Kitahara, Sawako Maeda, Kiyosumi Kashiwagi, Atsunori Uzu, Takashi Maegawa, Hiroshi Hypothalamic AMP-Activated Protein Kinase Regulates Biphasic Insulin Secretion from Pancreatic β Cells during Fasting and in Type 2 Diabetes |
title | Hypothalamic AMP-Activated Protein Kinase Regulates Biphasic Insulin Secretion from Pancreatic β Cells during Fasting and in Type 2 Diabetes |
title_full | Hypothalamic AMP-Activated Protein Kinase Regulates Biphasic Insulin Secretion from Pancreatic β Cells during Fasting and in Type 2 Diabetes |
title_fullStr | Hypothalamic AMP-Activated Protein Kinase Regulates Biphasic Insulin Secretion from Pancreatic β Cells during Fasting and in Type 2 Diabetes |
title_full_unstemmed | Hypothalamic AMP-Activated Protein Kinase Regulates Biphasic Insulin Secretion from Pancreatic β Cells during Fasting and in Type 2 Diabetes |
title_short | Hypothalamic AMP-Activated Protein Kinase Regulates Biphasic Insulin Secretion from Pancreatic β Cells during Fasting and in Type 2 Diabetes |
title_sort | hypothalamic amp-activated protein kinase regulates biphasic insulin secretion from pancreatic β cells during fasting and in type 2 diabetes |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264491/ https://www.ncbi.nlm.nih.gov/pubmed/28005533 http://dx.doi.org/10.1016/j.ebiom.2016.10.038 |
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