High-Fat Diet Augments VPAC1 Receptor-Mediated PACAP Action on the Liver, Inducing LAR Expression and Insulin Resistance
Pituitary adenylate cyclase-activating polypeptide (PACAP) acts on multiple processes of glucose and energy metabolism. PACAP potentiates insulin action in adipocytes and insulin release from pancreatic β-cells, thereby enhancing glucose tolerance. Contrary to these effects at organ levels, PACAP nu...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/9321395 |
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| author | Masanori Nakata Boyang Zhang Yifei Yang Takashi Okada Norihito Shintani Hitoshi Hashimoto Toshihiko Yada |
| author_facet | Masanori Nakata Boyang Zhang Yifei Yang Takashi Okada Norihito Shintani Hitoshi Hashimoto Toshihiko Yada |
| author_sort | Masanori Nakata |
| collection | DOAJ |
| description | Pituitary adenylate cyclase-activating polypeptide (PACAP) acts on multiple processes of glucose and energy metabolism. PACAP potentiates insulin action in adipocytes and insulin release from pancreatic β-cells, thereby enhancing glucose tolerance. Contrary to these effects at organ levels, PACAP null mice exhibit hypersensitivity to insulin. However, this apparent discrepancy remains to be solved. We aimed to clarify the mechanism underlying the antidiabetic phenotype of PACAP null mice. Feeding with high-fat diet (HFD) impaired insulin sensitivity and glucose tolerance in wild type mice, whereas these changes were prevented in PACAP null mice. HFD also impaired insulin-induced Akt phosphorylation in the liver in wild type mice, but not in PACAP null mice. Using GeneFishing method, HFD increased the leukocyte common antigen-related (LAR) protein tyrosine phosphatase in the liver in wild type mice. Silencing of LAR restored the insulin signaling in the liver of HFD mice. Moreover, the increased LAR expression by HFD was prevented in PACAP null mice. HFD increased the expression of VPAC1 receptor (VPAC1-R), one of three PACAP receptors, in the liver of wild type mice. These data indicate that PACAP-VPAC1-R signaling induces LAR expression and insulin resistance in the liver of HFD mice. Antagonism of VPAC1-R may prevent progression of HFD-induced insulin resistance in the liver, providing a novel antidiabetic strategy. |
| format | Article |
| id | doaj-art-200102f07a444f6784ef8fc64634172e |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-200102f07a444f6784ef8fc64634172e2025-02-03T01:31:23ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/93213959321395High-Fat Diet Augments VPAC1 Receptor-Mediated PACAP Action on the Liver, Inducing LAR Expression and Insulin ResistanceMasanori Nakata0Boyang Zhang1Yifei Yang2Takashi Okada3Norihito Shintani4Hitoshi Hashimoto5Toshihiko Yada6Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, JapanDepartment of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, JapanDepartment of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, JapanDepartment of Biochemistry and Molecular Biology, Division of Gene Therapy, Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo 113-8603, JapanLaboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, JapanLaboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, JapanDepartment of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, JapanPituitary adenylate cyclase-activating polypeptide (PACAP) acts on multiple processes of glucose and energy metabolism. PACAP potentiates insulin action in adipocytes and insulin release from pancreatic β-cells, thereby enhancing glucose tolerance. Contrary to these effects at organ levels, PACAP null mice exhibit hypersensitivity to insulin. However, this apparent discrepancy remains to be solved. We aimed to clarify the mechanism underlying the antidiabetic phenotype of PACAP null mice. Feeding with high-fat diet (HFD) impaired insulin sensitivity and glucose tolerance in wild type mice, whereas these changes were prevented in PACAP null mice. HFD also impaired insulin-induced Akt phosphorylation in the liver in wild type mice, but not in PACAP null mice. Using GeneFishing method, HFD increased the leukocyte common antigen-related (LAR) protein tyrosine phosphatase in the liver in wild type mice. Silencing of LAR restored the insulin signaling in the liver of HFD mice. Moreover, the increased LAR expression by HFD was prevented in PACAP null mice. HFD increased the expression of VPAC1 receptor (VPAC1-R), one of three PACAP receptors, in the liver of wild type mice. These data indicate that PACAP-VPAC1-R signaling induces LAR expression and insulin resistance in the liver of HFD mice. Antagonism of VPAC1-R may prevent progression of HFD-induced insulin resistance in the liver, providing a novel antidiabetic strategy.http://dx.doi.org/10.1155/2016/9321395 |
| spellingShingle | Masanori Nakata Boyang Zhang Yifei Yang Takashi Okada Norihito Shintani Hitoshi Hashimoto Toshihiko Yada High-Fat Diet Augments VPAC1 Receptor-Mediated PACAP Action on the Liver, Inducing LAR Expression and Insulin Resistance Journal of Diabetes Research |
| title | High-Fat Diet Augments VPAC1 Receptor-Mediated PACAP Action on the Liver, Inducing LAR Expression and Insulin Resistance |
| title_full | High-Fat Diet Augments VPAC1 Receptor-Mediated PACAP Action on the Liver, Inducing LAR Expression and Insulin Resistance |
| title_fullStr | High-Fat Diet Augments VPAC1 Receptor-Mediated PACAP Action on the Liver, Inducing LAR Expression and Insulin Resistance |
| title_full_unstemmed | High-Fat Diet Augments VPAC1 Receptor-Mediated PACAP Action on the Liver, Inducing LAR Expression and Insulin Resistance |
| title_short | High-Fat Diet Augments VPAC1 Receptor-Mediated PACAP Action on the Liver, Inducing LAR Expression and Insulin Resistance |
| title_sort | high fat diet augments vpac1 receptor mediated pacap action on the liver inducing lar expression and insulin resistance |
| url | http://dx.doi.org/10.1155/2016/9321395 |
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