Orexin A regulates plasma insulin and leptin levels in a time-dependent manner following a glucose load in mice
Aims/hypothesis Orexin A (OXA) is a neuropeptide implicated in the regulation of arousal status and energy metabolism. Orexin receptors are expressed not only in the central nervous system but also in the pancreas and adipose tissue. However, little is known about the physiological function of orexi...
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| Veröffentlicht in: | Diabetologia 2015-07, Vol.58 (7), p.1542-1550 |
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| creator | Park, Jae-Hyung Shim, Hae-Min Na, Ann-Yae Bae, Jae-Hoon Im, Seung-Soon Song, Dae-Kyu |
| description | Aims/hypothesis
Orexin A (OXA) is a neuropeptide implicated in the regulation of arousal status and energy metabolism. Orexin receptors are expressed not only in the central nervous system but also in the pancreas and adipose tissue. However, little is known about the physiological function of orexins. This study investigated the role of exogenous OXA in blood glucose control after glucose load in mice. In addition, the effect of OXA on insulin secretion was also identified in mouse pancreatic beta cells.
Methods
Insulin secretion and intracellular Ca
2+
levels were measured in perifused mouse islets. To investigate the effects of exogenous OXA on blood glucose levels in vivo, intraperitoneal glucose tolerance tests were performed after a subcutaneous injection of OXA in normal and high-fat diet-induced diabetic mice.
Results
OXA significantly potentiated glucose-stimulated insulin secretion in vitro, which increased intracellular Ca
2+
levels, mainly through adenylate cyclase and ryanodine receptor activation. This Ca
2+
-dependent insulinotropic effect of OXA was blocked in
Epac2
(
Rapgef4
)-deficient beta cells. After a glucose load in mice, exogenous OXA decreased blood glucose levels, compared with the control, by enhancing plasma insulin and decreasing plasma glucagon levels. Additionally, OXA caused a delayed increase in plasma leptin levels, resulting in lower plasma insulin levels when blood glucose levels fell to baseline.
Conclusions/interpretation
These results suggest that OXA might be a critical regulator of insulin, glucagon and leptin secretion in response to glucose. Thus, exogenous OXA might have therapeutic potential in improving blood glucose control in patients with type 2 diabetes. |
| doi_str_mv | 10.1007/s00125-015-3573-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1690210428</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3719687231</sourcerecordid><originalsourceid>FETCH-LOGICAL-c551t-658416814066f31278fa035b3a311675031812f066faca6f48380812d5f4508a3</originalsourceid><addsrcrecordid>eNp1kcFrFTEQxoMo9rX6B3iRgBcv0Zlkk5d3LEVtodCLgreQ7s4-tmSTbbJb639vlteWIvSUMN_vmxnmY-wDwhcE2H4tACi1ANRC6a0S8IptsFFSQCPta7ZZZYHW_D5ix6XcAIDSjXnLjqS2qCTqDUtXme6HyE95pv0S_EyFT8GX0fMhliVUyceOB5rm-g10R6HwtcjnYSTR0USxozjz0cdImfcphPRniPtK7MPSpkI8JN-tnnFo6R170_tQ6P3De8J-ff_28-xcXF79uDg7vRSt1jgLo22DxmIDxvQK5db2vi5_rbxCNFsNCi3KflV9603fWGWhVjrdNxqsVyfs86HvlNPtQmV241BaCsFHSktxaHYgcb1TRT_9h96kJce6XaXszgLudlApPFBtTqVk6t2Uh9Hnvw7BrWm4QxqupuHWNNzq-fjQebkeqXtyPJ6_AvIAlCrFPeVno1_s-g-GpZKc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1689801990</pqid></control><display><type>article</type><title>Orexin A regulates plasma insulin and leptin levels in a time-dependent manner following a glucose load in mice</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Park, Jae-Hyung ; Shim, Hae-Min ; Na, Ann-Yae ; Bae, Jae-Hoon ; Im, Seung-Soon ; Song, Dae-Kyu</creator><creatorcontrib>Park, Jae-Hyung ; Shim, Hae-Min ; Na, Ann-Yae ; Bae, Jae-Hoon ; Im, Seung-Soon ; Song, Dae-Kyu</creatorcontrib><description>Aims/hypothesis
Orexin A (OXA) is a neuropeptide implicated in the regulation of arousal status and energy metabolism. Orexin receptors are expressed not only in the central nervous system but also in the pancreas and adipose tissue. However, little is known about the physiological function of orexins. This study investigated the role of exogenous OXA in blood glucose control after glucose load in mice. In addition, the effect of OXA on insulin secretion was also identified in mouse pancreatic beta cells.
Methods
Insulin secretion and intracellular Ca
2+
levels were measured in perifused mouse islets. To investigate the effects of exogenous OXA on blood glucose levels in vivo, intraperitoneal glucose tolerance tests were performed after a subcutaneous injection of OXA in normal and high-fat diet-induced diabetic mice.
Results
OXA significantly potentiated glucose-stimulated insulin secretion in vitro, which increased intracellular Ca
2+
levels, mainly through adenylate cyclase and ryanodine receptor activation. This Ca
2+
-dependent insulinotropic effect of OXA was blocked in
Epac2
(
Rapgef4
)-deficient beta cells. After a glucose load in mice, exogenous OXA decreased blood glucose levels, compared with the control, by enhancing plasma insulin and decreasing plasma glucagon levels. Additionally, OXA caused a delayed increase in plasma leptin levels, resulting in lower plasma insulin levels when blood glucose levels fell to baseline.
Conclusions/interpretation
These results suggest that OXA might be a critical regulator of insulin, glucagon and leptin secretion in response to glucose. Thus, exogenous OXA might have therapeutic potential in improving blood glucose control in patients with type 2 diabetes.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-015-3573-0</identifier><identifier>PMID: 25813215</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Blood Glucose - metabolism ; Calcium - metabolism ; Diabetes ; Diabetes Mellitus, Type 2 - metabolism ; Diet, High-Fat ; Glucagon ; Glucagon - blood ; Glucose ; Glucose - pharmacology ; Glucose Tolerance Test ; Guanine Nucleotide Exchange Factors - genetics ; Guanine Nucleotide Exchange Factors - physiology ; Human Physiology ; Insulin - blood ; Insulin - metabolism ; Insulin resistance ; Insulin-Secreting Cells - drug effects ; Insulin-Secreting Cells - metabolism ; Internal Medicine ; Islets of Langerhans - cytology ; Islets of Langerhans - drug effects ; Islets of Langerhans - metabolism ; Kinases ; Leptin - blood ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Metabolism ; Mice ; Mice, Inbred C57BL ; Nervous system ; Obesity ; Orexin Receptors - drug effects ; Orexins - pharmacology ; Pancreas ; Plasma ; Proteins</subject><ispartof>Diabetologia, 2015-07, Vol.58 (7), p.1542-1550</ispartof><rights>Springer-Verlag Berlin Heidelberg 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c551t-658416814066f31278fa035b3a311675031812f066faca6f48380812d5f4508a3</citedby><cites>FETCH-LOGICAL-c551t-658416814066f31278fa035b3a311675031812f066faca6f48380812d5f4508a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-015-3573-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-015-3573-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25813215$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Jae-Hyung</creatorcontrib><creatorcontrib>Shim, Hae-Min</creatorcontrib><creatorcontrib>Na, Ann-Yae</creatorcontrib><creatorcontrib>Bae, Jae-Hoon</creatorcontrib><creatorcontrib>Im, Seung-Soon</creatorcontrib><creatorcontrib>Song, Dae-Kyu</creatorcontrib><title>Orexin A regulates plasma insulin and leptin levels in a time-dependent manner following a glucose load in mice</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
Orexin A (OXA) is a neuropeptide implicated in the regulation of arousal status and energy metabolism. Orexin receptors are expressed not only in the central nervous system but also in the pancreas and adipose tissue. However, little is known about the physiological function of orexins. This study investigated the role of exogenous OXA in blood glucose control after glucose load in mice. In addition, the effect of OXA on insulin secretion was also identified in mouse pancreatic beta cells.
Methods
Insulin secretion and intracellular Ca
2+
levels were measured in perifused mouse islets. To investigate the effects of exogenous OXA on blood glucose levels in vivo, intraperitoneal glucose tolerance tests were performed after a subcutaneous injection of OXA in normal and high-fat diet-induced diabetic mice.
Results
OXA significantly potentiated glucose-stimulated insulin secretion in vitro, which increased intracellular Ca
2+
levels, mainly through adenylate cyclase and ryanodine receptor activation. This Ca
2+
-dependent insulinotropic effect of OXA was blocked in
Epac2
(
Rapgef4
)-deficient beta cells. After a glucose load in mice, exogenous OXA decreased blood glucose levels, compared with the control, by enhancing plasma insulin and decreasing plasma glucagon levels. Additionally, OXA caused a delayed increase in plasma leptin levels, resulting in lower plasma insulin levels when blood glucose levels fell to baseline.
Conclusions/interpretation
These results suggest that OXA might be a critical regulator of insulin, glucagon and leptin secretion in response to glucose. Thus, exogenous OXA might have therapeutic potential in improving blood glucose control in patients with type 2 diabetes.</description><subject>Animals</subject><subject>Blood Glucose - metabolism</subject><subject>Calcium - metabolism</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diet, High-Fat</subject><subject>Glucagon</subject><subject>Glucagon - blood</subject><subject>Glucose</subject><subject>Glucose - pharmacology</subject><subject>Glucose Tolerance Test</subject><subject>Guanine Nucleotide Exchange Factors - genetics</subject><subject>Guanine Nucleotide Exchange Factors - physiology</subject><subject>Human Physiology</subject><subject>Insulin - blood</subject><subject>Insulin - metabolism</subject><subject>Insulin resistance</subject><subject>Insulin-Secreting Cells - drug effects</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Internal Medicine</subject><subject>Islets of Langerhans - cytology</subject><subject>Islets of Langerhans - drug effects</subject><subject>Islets of Langerhans - metabolism</subject><subject>Kinases</subject><subject>Leptin - blood</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Nervous system</subject><subject>Obesity</subject><subject>Orexin Receptors - drug effects</subject><subject>Orexins - pharmacology</subject><subject>Pancreas</subject><subject>Plasma</subject><subject>Proteins</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kcFrFTEQxoMo9rX6B3iRgBcv0Zlkk5d3LEVtodCLgreQ7s4-tmSTbbJb639vlteWIvSUMN_vmxnmY-wDwhcE2H4tACi1ANRC6a0S8IptsFFSQCPta7ZZZYHW_D5ix6XcAIDSjXnLjqS2qCTqDUtXme6HyE95pv0S_EyFT8GX0fMhliVUyceOB5rm-g10R6HwtcjnYSTR0USxozjz0cdImfcphPRniPtK7MPSpkI8JN-tnnFo6R170_tQ6P3De8J-ff_28-xcXF79uDg7vRSt1jgLo22DxmIDxvQK5db2vi5_rbxCNFsNCi3KflV9603fWGWhVjrdNxqsVyfs86HvlNPtQmV241BaCsFHSktxaHYgcb1TRT_9h96kJce6XaXszgLudlApPFBtTqVk6t2Uh9Hnvw7BrWm4QxqupuHWNNzq-fjQebkeqXtyPJ6_AvIAlCrFPeVno1_s-g-GpZKc</recordid><startdate>20150701</startdate><enddate>20150701</enddate><creator>Park, Jae-Hyung</creator><creator>Shim, Hae-Min</creator><creator>Na, Ann-Yae</creator><creator>Bae, Jae-Hoon</creator><creator>Im, Seung-Soon</creator><creator>Song, Dae-Kyu</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20150701</creationdate><title>Orexin A regulates plasma insulin and leptin levels in a time-dependent manner following a glucose load in mice</title><author>Park, Jae-Hyung ; Shim, Hae-Min ; Na, Ann-Yae ; Bae, Jae-Hoon ; Im, Seung-Soon ; Song, Dae-Kyu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c551t-658416814066f31278fa035b3a311675031812f066faca6f48380812d5f4508a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Blood Glucose - metabolism</topic><topic>Calcium - metabolism</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diet, High-Fat</topic><topic>Glucagon</topic><topic>Glucagon - blood</topic><topic>Glucose</topic><topic>Glucose - pharmacology</topic><topic>Glucose Tolerance Test</topic><topic>Guanine Nucleotide Exchange Factors - genetics</topic><topic>Guanine Nucleotide Exchange Factors - physiology</topic><topic>Human Physiology</topic><topic>Insulin - blood</topic><topic>Insulin - metabolism</topic><topic>Insulin resistance</topic><topic>Insulin-Secreting Cells - drug effects</topic><topic>Insulin-Secreting Cells - metabolism</topic><topic>Internal Medicine</topic><topic>Islets of Langerhans - cytology</topic><topic>Islets of Langerhans - drug effects</topic><topic>Islets of Langerhans - metabolism</topic><topic>Kinases</topic><topic>Leptin - blood</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Nervous system</topic><topic>Obesity</topic><topic>Orexin Receptors - drug effects</topic><topic>Orexins - pharmacology</topic><topic>Pancreas</topic><topic>Plasma</topic><topic>Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Jae-Hyung</creatorcontrib><creatorcontrib>Shim, Hae-Min</creatorcontrib><creatorcontrib>Na, Ann-Yae</creatorcontrib><creatorcontrib>Bae, Jae-Hoon</creatorcontrib><creatorcontrib>Im, Seung-Soon</creatorcontrib><creatorcontrib>Song, Dae-Kyu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Jae-Hyung</au><au>Shim, Hae-Min</au><au>Na, Ann-Yae</au><au>Bae, Jae-Hoon</au><au>Im, Seung-Soon</au><au>Song, Dae-Kyu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Orexin A regulates plasma insulin and leptin levels in a time-dependent manner following a glucose load in mice</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2015-07-01</date><risdate>2015</risdate><volume>58</volume><issue>7</issue><spage>1542</spage><epage>1550</epage><pages>1542-1550</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
Orexin A (OXA) is a neuropeptide implicated in the regulation of arousal status and energy metabolism. Orexin receptors are expressed not only in the central nervous system but also in the pancreas and adipose tissue. However, little is known about the physiological function of orexins. This study investigated the role of exogenous OXA in blood glucose control after glucose load in mice. In addition, the effect of OXA on insulin secretion was also identified in mouse pancreatic beta cells.
Methods
Insulin secretion and intracellular Ca
2+
levels were measured in perifused mouse islets. To investigate the effects of exogenous OXA on blood glucose levels in vivo, intraperitoneal glucose tolerance tests were performed after a subcutaneous injection of OXA in normal and high-fat diet-induced diabetic mice.
Results
OXA significantly potentiated glucose-stimulated insulin secretion in vitro, which increased intracellular Ca
2+
levels, mainly through adenylate cyclase and ryanodine receptor activation. This Ca
2+
-dependent insulinotropic effect of OXA was blocked in
Epac2
(
Rapgef4
)-deficient beta cells. After a glucose load in mice, exogenous OXA decreased blood glucose levels, compared with the control, by enhancing plasma insulin and decreasing plasma glucagon levels. Additionally, OXA caused a delayed increase in plasma leptin levels, resulting in lower plasma insulin levels when blood glucose levels fell to baseline.
Conclusions/interpretation
These results suggest that OXA might be a critical regulator of insulin, glucagon and leptin secretion in response to glucose. Thus, exogenous OXA might have therapeutic potential in improving blood glucose control in patients with type 2 diabetes.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>25813215</pmid><doi>10.1007/s00125-015-3573-0</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Diabetologia, 2015-07, Vol.58 (7), p.1542-1550 |
| issn | 0012-186X 1432-0428 |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Animals Blood Glucose - metabolism Calcium - metabolism Diabetes Diabetes Mellitus, Type 2 - metabolism Diet, High-Fat Glucagon Glucagon - blood Glucose Glucose - pharmacology Glucose Tolerance Test Guanine Nucleotide Exchange Factors - genetics Guanine Nucleotide Exchange Factors - physiology Human Physiology Insulin - blood Insulin - metabolism Insulin resistance Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - metabolism Internal Medicine Islets of Langerhans - cytology Islets of Langerhans - drug effects Islets of Langerhans - metabolism Kinases Leptin - blood Medicine Medicine & Public Health Metabolic Diseases Metabolism Mice Mice, Inbred C57BL Nervous system Obesity Orexin Receptors - drug effects Orexins - pharmacology Pancreas Plasma Proteins |
| title | Orexin A regulates plasma insulin and leptin levels in a time-dependent manner following a glucose load in mice |
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