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...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-11-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396416304996 |
| _version_ | 1811217173485453312 |
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| author | Shinji Kume Motoyuki Kondo Shiro Maeda Yoshihiko Nishio Tsuyoshi Yanagimachi Yukihiro Fujita Masakazu Haneda Keiko Kondo Akihiro Sekine Shin-ich Araki Hisazumi Araki Masami Chin-Kanasaki Satoshi Ugi Daisuke Koya Sawako Kitahara Kiyosumi Maeda Atsunori Kashiwagi Takashi Uzu Hiroshi Maegawa |
| author_facet | Shinji Kume Motoyuki Kondo Shiro Maeda Yoshihiko Nishio Tsuyoshi Yanagimachi Yukihiro Fujita Masakazu Haneda Keiko Kondo Akihiro Sekine Shin-ich Araki Hisazumi Araki Masami Chin-Kanasaki Satoshi Ugi Daisuke Koya Sawako Kitahara Kiyosumi Maeda Atsunori Kashiwagi Takashi Uzu Hiroshi Maegawa |
| author_sort | Shinji Kume |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T06:49:29Z |
| format | Article |
| id | doaj.art-c4a2d37bf79445679e5e611de986dd55 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-12T06:49:29Z |
| publishDate | 2016-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-c4a2d37bf79445679e5e611de986dd552022-12-22T03:43:24ZengElsevierEBioMedicine2352-39642016-11-0113C16818010.1016/j.ebiom.2016.10.038Hypothalamic AMP-Activated Protein Kinase Regulates Biphasic Insulin Secretion from Pancreatic β Cells during Fasting and in Type 2 DiabetesShinji Kume0Motoyuki Kondo1Shiro Maeda2Yoshihiko Nishio3Tsuyoshi Yanagimachi4Yukihiro Fujita5Masakazu Haneda6Keiko Kondo7Akihiro Sekine8Shin-ich Araki9Hisazumi Araki10Masami Chin-Kanasaki11Satoshi Ugi12Daisuke Koya13Sawako Kitahara14Kiyosumi Maeda15Atsunori Kashiwagi16Takashi Uzu17Hiroshi Maegawa18Department of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanDepartment of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanLaboratory for Endocrinology and Metabolism, RIKEN Center for Genomic Medicine, Yokohama, Kanagawa 230-0045, JapanDivision of Diabetes, Metabolism and Endocrinology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka, Kagoshima 890-8580, JapanDivision of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido 078-8510, JapanDivision of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido 078-8510, JapanDivision of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido 078-8510, JapanDepartment of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanChiba University, Center for Preventive Medical Science. 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba, 260-0856, JapanDepartment of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanDepartment of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanDepartment of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanDepartment of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanDivision of Diabetology & Endocrinology, Kanazawa Medical University, Kahoku-gun, Ishikawa 920-1192, JapanKusatsu General Hospital, Kusatsu, Shiga 525-0066, JapanKusatsu General Hospital, Kusatsu, Shiga 525-0066, JapanDepartment of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanDepartment of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanDepartment of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanGlucose-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.http://www.sciencedirect.com/science/article/pii/S2352396416304996First-phase GSISPancreatic β cellStarvationDiabetesInsulin secretion |
| spellingShingle | Shinji Kume Motoyuki Kondo Shiro Maeda Yoshihiko Nishio Tsuyoshi Yanagimachi Yukihiro Fujita Masakazu Haneda Keiko Kondo Akihiro Sekine Shin-ich Araki Hisazumi Araki Masami Chin-Kanasaki Satoshi Ugi Daisuke Koya Sawako Kitahara Kiyosumi Maeda Atsunori Kashiwagi Takashi Uzu Hiroshi Maegawa Hypothalamic AMP-Activated Protein Kinase Regulates Biphasic Insulin Secretion from Pancreatic β Cells during Fasting and in Type 2 Diabetes EBioMedicine First-phase GSIS Pancreatic β cell Starvation Diabetes Insulin secretion |
| 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 | First-phase GSIS Pancreatic β cell Starvation Diabetes Insulin secretion |
| url | http://www.sciencedirect.com/science/article/pii/S2352396416304996 |
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