Insulin potentiates the response to capsaicin in dorsal root ganglion neurons in vitro and muscle afferents ex vivo in normal healthy rodents
Systemic insulin administration evokes sympathoexcitatory actions, but the mechanisms underlying these observations are unknown. We reported that insulin sensitizes the response of thin‐fibre primary afferents, as well as the dorsal root ganglion (DRG) that subserves them, to mechanical stimuli. How...
Gespeichert in:
| Veröffentlicht in: | The Journal of physiology 2022-02, Vol.600 (3), p.531-545 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 545 |
|---|---|
| container_issue | 3 |
| container_start_page | 531 |
| container_title | The Journal of physiology |
| container_volume | 600 |
| creator | Hori, Amane Hotta, Norio Fukazawa, Ayumi Estrada, Juan A. Katanosaka, Kimiaki Mizumura, Kazue Sato, Jun Ishizawa, Rie Kim, Han‐Kyul Iwamoto, Gary A. Vongpatanasin, Wanpen Mitchell, Jere H. Smith, Scott A. Mizuno, Masaki |
| description | Systemic insulin administration evokes sympathoexcitatory actions, but the mechanisms underlying these observations are unknown. We reported that insulin sensitizes the response of thin‐fibre primary afferents, as well as the dorsal root ganglion (DRG) that subserves them, to mechanical stimuli. However, little is known about the effects of insulin on primary neuronal responses to chemical stimuli. TRPV1, whose agonist is capsaicin (CAP), is widely expressed on chemically sensitive metaboreceptors and/or nociceptors. The aim of this investigation was to determine the effects of insulin on CAP‐activated currents in small DRG neurons and CAP‐induced action potentials in thin‐fibre muscle afferents of normal healthy rodents. Additionally, we investigated whether insulin potentiates sympathetic nerve activity (SNA) responses to CAP. In whole‐cell patch‐clamp recordings from cultured mice DRG neurons in vitro, the fold change in CAP‐activated current from pre‐ to post‐application of insulin (n = 13) was significantly (P |
| doi_str_mv | 10.1113/JP282740 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8810710</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2623811745</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5440-ccd13ad72408acb92019e31ef143c8589aeecc21b98aa8b8f34278cc200829653</originalsourceid><addsrcrecordid>eNp1kV1rFDEUhoModq2Cv0AC3ngzNV8zSW4EKVZbCvaiXods5sxuSiYZk5nV_RH9z2bphx8gBAJ5H56cw4vQa0pOKKX8_cUVU0wK8gStqOh0I6XmT9GKEMYaLlt6hF6UckMI5UTr5-iIC91JIfgK3Z7HsgQf8ZRmiLO3MxQ8bwFnKFOKBfCcsLNTsd5Vqp4-5WIDzinNeGPjJvgUcYQlV_qQ7_ycE7axx-NSXABshwFydRcMP2u6SwcqpjxWyxZsmLf7ausPxEv0bLChwKv7-xh9O_t0ffqlufz6-fz042XjWiFI41xPue0lE0RZt9aMUA2cwkAFd6pV2gI4x-haK2vVWg1cMKnqCyGK6a7lx-jDnXda1iP0rv6dbTBT9qPNe5OsN38n0W_NJu2MUpRISqrg3b0gp-8LlNmMvjgIwUZISzGso62QsiOiom__QW_SkmNdr1KMK0qlaH8LXU6lZBgeh6HEHDo2Dx1X9M2fwz-CD6VW4OQO-OED7P8rMtcXV1ToavwFSYyyUQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2623811745</pqid></control><display><type>article</type><title>Insulin potentiates the response to capsaicin in dorsal root ganglion neurons in vitro and muscle afferents ex vivo in normal healthy rodents</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Wiley Online Library Free Content</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Hori, Amane ; Hotta, Norio ; Fukazawa, Ayumi ; Estrada, Juan A. ; Katanosaka, Kimiaki ; Mizumura, Kazue ; Sato, Jun ; Ishizawa, Rie ; Kim, Han‐Kyul ; Iwamoto, Gary A. ; Vongpatanasin, Wanpen ; Mitchell, Jere H. ; Smith, Scott A. ; Mizuno, Masaki</creator><creatorcontrib>Hori, Amane ; Hotta, Norio ; Fukazawa, Ayumi ; Estrada, Juan A. ; Katanosaka, Kimiaki ; Mizumura, Kazue ; Sato, Jun ; Ishizawa, Rie ; Kim, Han‐Kyul ; Iwamoto, Gary A. ; Vongpatanasin, Wanpen ; Mitchell, Jere H. ; Smith, Scott A. ; Mizuno, Masaki</creatorcontrib><description>Systemic insulin administration evokes sympathoexcitatory actions, but the mechanisms underlying these observations are unknown. We reported that insulin sensitizes the response of thin‐fibre primary afferents, as well as the dorsal root ganglion (DRG) that subserves them, to mechanical stimuli. However, little is known about the effects of insulin on primary neuronal responses to chemical stimuli. TRPV1, whose agonist is capsaicin (CAP), is widely expressed on chemically sensitive metaboreceptors and/or nociceptors. The aim of this investigation was to determine the effects of insulin on CAP‐activated currents in small DRG neurons and CAP‐induced action potentials in thin‐fibre muscle afferents of normal healthy rodents. Additionally, we investigated whether insulin potentiates sympathetic nerve activity (SNA) responses to CAP. In whole‐cell patch‐clamp recordings from cultured mice DRG neurons in vitro, the fold change in CAP‐activated current from pre‐ to post‐application of insulin (n = 13) was significantly (P < 0.05) higher than with a vehicle control (n = 14). Similar results were observed in single‐fibre recording experiments ex vivo as insulin potentiated CAP‐induced action potentials compared to vehicle controls (n = 9 per group, P < 0.05). Furthermore, insulin receptor blockade with GSK1838705 significantly suppressed the insulin‐induced augmentation in CAP‐activated currents (n = 13) as well as the response magnitude of CAP‐induced action potentials (n = 9). Likewise, the renal SNA response to CAP after intramuscular injection of insulin (n = 8) was significantly (P < 0.05) greater compared to vehicle (n = 9). The findings suggest that insulin potentiates TRPV1 responsiveness to CAP at the DRG and muscle tissue levels, possibly contributing to the augmentation in sympathoexcitation during activities such as physical exercise.
Key points
Evidence suggests insulin centrally activates the sympathetic nervous system, and a chemical stimulus to tissues activates the sympathetic nervous system via thin fibre muscle afferents.
Insulin is reported to modulate putative chemical‐sensitive channels in the dorsal root ganglion neurons of these afferents.
In the present study, it is demonstrated that insulin potentiates the responsiveness of thin fibre afferents to capsaicin at muscle tissue levels as well as at the level of dorsal root ganglion neurons. In addition, it is demonstrated that insulin augments the sympathetic nerve activity response to capsaicin in vivo.
These data suggest that sympathoexcitation is peripherally mediated via insulin‐induced chemical sensitization.
The present study proposes a possible physiological role of insulin in the regulation of chemical sensitivity in somatosensory thin fibre muscle afferents.
figure legend: Insulin‐induced enhancement of sympathetic nerve activity via sensitization of transient receptor potential vanilloid 1 (TRPV1) in small dorsal root ganglion (DRG) neurons and thin‐fibre muscle afferents. Insulin increases neural discharge in response to exposure to capsaicin, a TRPV1 agonist, in thin‐fibre afferents at the level of the DRG in vitro and the skeletal muscle axon terminal ex vivo via sensitization of TRPV1. Further, in vivo studies demonstrate that intramuscular injection of insulin augments sympathetic nerve activity and blood pressure responses to intra‐arterial injection of capsaicin. These findings suggest that insulin‐induced sensitization of TRPV1 may contribute to the augmentation in sympathoexcitation during activities such as physical exercise. Design made in BioRender.</description><identifier>ISSN: 0022-3751</identifier><identifier>EISSN: 1469-7793</identifier><identifier>DOI: 10.1113/JP282740</identifier><identifier>PMID: 34967443</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Animals ; Capsaicin ; Capsaicin - pharmacology ; Capsaicin receptors ; chemical sensitization ; Chemical stimuli ; Dorsal root ganglia ; exercise pressor reflex ; Ganglia, Spinal - physiology ; group IV muscle afferents ; hyperinsulinaemia ; Insulin ; Insulin - pharmacology ; Mechanical stimuli ; Mice ; Muscle Fibers, Skeletal ; Nervous system ; Neurons ; Neurons - physiology ; Nociceptors ; Pain perception ; primary sensory neuron ; Rats ; Rats, Sprague-Dawley ; Rodentia ; Sympathetic nerves ; Sympathetic nervous system ; transient receptor potential vanilloid 1 ; TRPV Cation Channels - physiology</subject><ispartof>The Journal of physiology, 2022-02, Vol.600 (3), p.531-545</ispartof><rights>2021 The Authors. The Journal of Physiology © 2021 The Physiological Society</rights><rights>2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.</rights><rights>Journal compilation © 2022 The Physiological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5440-ccd13ad72408acb92019e31ef143c8589aeecc21b98aa8b8f34278cc200829653</citedby><cites>FETCH-LOGICAL-c5440-ccd13ad72408acb92019e31ef143c8589aeecc21b98aa8b8f34278cc200829653</cites><orcidid>0000-0003-4455-8084 ; 0000-0003-1048-9543 ; 0000-0002-5554-0659 ; 0000-0002-4866-6536 ; 0000-0002-5853-5193 ; 0000-0002-7531-9388 ; 0000-0001-9450-9171 ; 0000-0002-2143-2342</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810710/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810710/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34967443$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hori, Amane</creatorcontrib><creatorcontrib>Hotta, Norio</creatorcontrib><creatorcontrib>Fukazawa, Ayumi</creatorcontrib><creatorcontrib>Estrada, Juan A.</creatorcontrib><creatorcontrib>Katanosaka, Kimiaki</creatorcontrib><creatorcontrib>Mizumura, Kazue</creatorcontrib><creatorcontrib>Sato, Jun</creatorcontrib><creatorcontrib>Ishizawa, Rie</creatorcontrib><creatorcontrib>Kim, Han‐Kyul</creatorcontrib><creatorcontrib>Iwamoto, Gary A.</creatorcontrib><creatorcontrib>Vongpatanasin, Wanpen</creatorcontrib><creatorcontrib>Mitchell, Jere H.</creatorcontrib><creatorcontrib>Smith, Scott A.</creatorcontrib><creatorcontrib>Mizuno, Masaki</creatorcontrib><title>Insulin potentiates the response to capsaicin in dorsal root ganglion neurons in vitro and muscle afferents ex vivo in normal healthy rodents</title><title>The Journal of physiology</title><addtitle>J Physiol</addtitle><description>Systemic insulin administration evokes sympathoexcitatory actions, but the mechanisms underlying these observations are unknown. We reported that insulin sensitizes the response of thin‐fibre primary afferents, as well as the dorsal root ganglion (DRG) that subserves them, to mechanical stimuli. However, little is known about the effects of insulin on primary neuronal responses to chemical stimuli. TRPV1, whose agonist is capsaicin (CAP), is widely expressed on chemically sensitive metaboreceptors and/or nociceptors. The aim of this investigation was to determine the effects of insulin on CAP‐activated currents in small DRG neurons and CAP‐induced action potentials in thin‐fibre muscle afferents of normal healthy rodents. Additionally, we investigated whether insulin potentiates sympathetic nerve activity (SNA) responses to CAP. In whole‐cell patch‐clamp recordings from cultured mice DRG neurons in vitro, the fold change in CAP‐activated current from pre‐ to post‐application of insulin (n = 13) was significantly (P < 0.05) higher than with a vehicle control (n = 14). Similar results were observed in single‐fibre recording experiments ex vivo as insulin potentiated CAP‐induced action potentials compared to vehicle controls (n = 9 per group, P < 0.05). Furthermore, insulin receptor blockade with GSK1838705 significantly suppressed the insulin‐induced augmentation in CAP‐activated currents (n = 13) as well as the response magnitude of CAP‐induced action potentials (n = 9). Likewise, the renal SNA response to CAP after intramuscular injection of insulin (n = 8) was significantly (P < 0.05) greater compared to vehicle (n = 9). The findings suggest that insulin potentiates TRPV1 responsiveness to CAP at the DRG and muscle tissue levels, possibly contributing to the augmentation in sympathoexcitation during activities such as physical exercise.
Key points
Evidence suggests insulin centrally activates the sympathetic nervous system, and a chemical stimulus to tissues activates the sympathetic nervous system via thin fibre muscle afferents.
Insulin is reported to modulate putative chemical‐sensitive channels in the dorsal root ganglion neurons of these afferents.
In the present study, it is demonstrated that insulin potentiates the responsiveness of thin fibre afferents to capsaicin at muscle tissue levels as well as at the level of dorsal root ganglion neurons. In addition, it is demonstrated that insulin augments the sympathetic nerve activity response to capsaicin in vivo.
These data suggest that sympathoexcitation is peripherally mediated via insulin‐induced chemical sensitization.
The present study proposes a possible physiological role of insulin in the regulation of chemical sensitivity in somatosensory thin fibre muscle afferents.
figure legend: Insulin‐induced enhancement of sympathetic nerve activity via sensitization of transient receptor potential vanilloid 1 (TRPV1) in small dorsal root ganglion (DRG) neurons and thin‐fibre muscle afferents. Insulin increases neural discharge in response to exposure to capsaicin, a TRPV1 agonist, in thin‐fibre afferents at the level of the DRG in vitro and the skeletal muscle axon terminal ex vivo via sensitization of TRPV1. Further, in vivo studies demonstrate that intramuscular injection of insulin augments sympathetic nerve activity and blood pressure responses to intra‐arterial injection of capsaicin. These findings suggest that insulin‐induced sensitization of TRPV1 may contribute to the augmentation in sympathoexcitation during activities such as physical exercise. Design made in BioRender.</description><subject>Animals</subject><subject>Capsaicin</subject><subject>Capsaicin - pharmacology</subject><subject>Capsaicin receptors</subject><subject>chemical sensitization</subject><subject>Chemical stimuli</subject><subject>Dorsal root ganglia</subject><subject>exercise pressor reflex</subject><subject>Ganglia, Spinal - physiology</subject><subject>group IV muscle afferents</subject><subject>hyperinsulinaemia</subject><subject>Insulin</subject><subject>Insulin - pharmacology</subject><subject>Mechanical stimuli</subject><subject>Mice</subject><subject>Muscle Fibers, Skeletal</subject><subject>Nervous system</subject><subject>Neurons</subject><subject>Neurons - physiology</subject><subject>Nociceptors</subject><subject>Pain perception</subject><subject>primary sensory neuron</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodentia</subject><subject>Sympathetic nerves</subject><subject>Sympathetic nervous system</subject><subject>transient receptor potential vanilloid 1</subject><subject>TRPV Cation Channels - physiology</subject><issn>0022-3751</issn><issn>1469-7793</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kV1rFDEUhoModq2Cv0AC3ngzNV8zSW4EKVZbCvaiXods5sxuSiYZk5nV_RH9z2bphx8gBAJ5H56cw4vQa0pOKKX8_cUVU0wK8gStqOh0I6XmT9GKEMYaLlt6hF6UckMI5UTr5-iIC91JIfgK3Z7HsgQf8ZRmiLO3MxQ8bwFnKFOKBfCcsLNTsd5Vqp4-5WIDzinNeGPjJvgUcYQlV_qQ7_ycE7axx-NSXABshwFydRcMP2u6SwcqpjxWyxZsmLf7ausPxEv0bLChwKv7-xh9O_t0ffqlufz6-fz042XjWiFI41xPue0lE0RZt9aMUA2cwkAFd6pV2gI4x-haK2vVWg1cMKnqCyGK6a7lx-jDnXda1iP0rv6dbTBT9qPNe5OsN38n0W_NJu2MUpRISqrg3b0gp-8LlNmMvjgIwUZISzGso62QsiOiom__QW_SkmNdr1KMK0qlaH8LXU6lZBgeh6HEHDo2Dx1X9M2fwz-CD6VW4OQO-OED7P8rMtcXV1ToavwFSYyyUQ</recordid><startdate>20220201</startdate><enddate>20220201</enddate><creator>Hori, Amane</creator><creator>Hotta, Norio</creator><creator>Fukazawa, Ayumi</creator><creator>Estrada, Juan A.</creator><creator>Katanosaka, Kimiaki</creator><creator>Mizumura, Kazue</creator><creator>Sato, Jun</creator><creator>Ishizawa, Rie</creator><creator>Kim, Han‐Kyul</creator><creator>Iwamoto, Gary A.</creator><creator>Vongpatanasin, Wanpen</creator><creator>Mitchell, Jere H.</creator><creator>Smith, Scott A.</creator><creator>Mizuno, Masaki</creator><general>Wiley Subscription Services, Inc</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TS</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4455-8084</orcidid><orcidid>https://orcid.org/0000-0003-1048-9543</orcidid><orcidid>https://orcid.org/0000-0002-5554-0659</orcidid><orcidid>https://orcid.org/0000-0002-4866-6536</orcidid><orcidid>https://orcid.org/0000-0002-5853-5193</orcidid><orcidid>https://orcid.org/0000-0002-7531-9388</orcidid><orcidid>https://orcid.org/0000-0001-9450-9171</orcidid><orcidid>https://orcid.org/0000-0002-2143-2342</orcidid></search><sort><creationdate>20220201</creationdate><title>Insulin potentiates the response to capsaicin in dorsal root ganglion neurons in vitro and muscle afferents ex vivo in normal healthy rodents</title><author>Hori, Amane ; Hotta, Norio ; Fukazawa, Ayumi ; Estrada, Juan A. ; Katanosaka, Kimiaki ; Mizumura, Kazue ; Sato, Jun ; Ishizawa, Rie ; Kim, Han‐Kyul ; Iwamoto, Gary A. ; Vongpatanasin, Wanpen ; Mitchell, Jere H. ; Smith, Scott A. ; Mizuno, Masaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5440-ccd13ad72408acb92019e31ef143c8589aeecc21b98aa8b8f34278cc200829653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Capsaicin</topic><topic>Capsaicin - pharmacology</topic><topic>Capsaicin receptors</topic><topic>chemical sensitization</topic><topic>Chemical stimuli</topic><topic>Dorsal root ganglia</topic><topic>exercise pressor reflex</topic><topic>Ganglia, Spinal - physiology</topic><topic>group IV muscle afferents</topic><topic>hyperinsulinaemia</topic><topic>Insulin</topic><topic>Insulin - pharmacology</topic><topic>Mechanical stimuli</topic><topic>Mice</topic><topic>Muscle Fibers, Skeletal</topic><topic>Nervous system</topic><topic>Neurons</topic><topic>Neurons - physiology</topic><topic>Nociceptors</topic><topic>Pain perception</topic><topic>primary sensory neuron</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rodentia</topic><topic>Sympathetic nerves</topic><topic>Sympathetic nervous system</topic><topic>transient receptor potential vanilloid 1</topic><topic>TRPV Cation Channels - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hori, Amane</creatorcontrib><creatorcontrib>Hotta, Norio</creatorcontrib><creatorcontrib>Fukazawa, Ayumi</creatorcontrib><creatorcontrib>Estrada, Juan A.</creatorcontrib><creatorcontrib>Katanosaka, Kimiaki</creatorcontrib><creatorcontrib>Mizumura, Kazue</creatorcontrib><creatorcontrib>Sato, Jun</creatorcontrib><creatorcontrib>Ishizawa, Rie</creatorcontrib><creatorcontrib>Kim, Han‐Kyul</creatorcontrib><creatorcontrib>Iwamoto, Gary A.</creatorcontrib><creatorcontrib>Vongpatanasin, Wanpen</creatorcontrib><creatorcontrib>Mitchell, Jere H.</creatorcontrib><creatorcontrib>Smith, Scott A.</creatorcontrib><creatorcontrib>Mizuno, Masaki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hori, Amane</au><au>Hotta, Norio</au><au>Fukazawa, Ayumi</au><au>Estrada, Juan A.</au><au>Katanosaka, Kimiaki</au><au>Mizumura, Kazue</au><au>Sato, Jun</au><au>Ishizawa, Rie</au><au>Kim, Han‐Kyul</au><au>Iwamoto, Gary A.</au><au>Vongpatanasin, Wanpen</au><au>Mitchell, Jere H.</au><au>Smith, Scott A.</au><au>Mizuno, Masaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Insulin potentiates the response to capsaicin in dorsal root ganglion neurons in vitro and muscle afferents ex vivo in normal healthy rodents</atitle><jtitle>The Journal of physiology</jtitle><addtitle>J Physiol</addtitle><date>2022-02-01</date><risdate>2022</risdate><volume>600</volume><issue>3</issue><spage>531</spage><epage>545</epage><pages>531-545</pages><issn>0022-3751</issn><eissn>1469-7793</eissn><abstract>Systemic insulin administration evokes sympathoexcitatory actions, but the mechanisms underlying these observations are unknown. We reported that insulin sensitizes the response of thin‐fibre primary afferents, as well as the dorsal root ganglion (DRG) that subserves them, to mechanical stimuli. However, little is known about the effects of insulin on primary neuronal responses to chemical stimuli. TRPV1, whose agonist is capsaicin (CAP), is widely expressed on chemically sensitive metaboreceptors and/or nociceptors. The aim of this investigation was to determine the effects of insulin on CAP‐activated currents in small DRG neurons and CAP‐induced action potentials in thin‐fibre muscle afferents of normal healthy rodents. Additionally, we investigated whether insulin potentiates sympathetic nerve activity (SNA) responses to CAP. In whole‐cell patch‐clamp recordings from cultured mice DRG neurons in vitro, the fold change in CAP‐activated current from pre‐ to post‐application of insulin (n = 13) was significantly (P < 0.05) higher than with a vehicle control (n = 14). Similar results were observed in single‐fibre recording experiments ex vivo as insulin potentiated CAP‐induced action potentials compared to vehicle controls (n = 9 per group, P < 0.05). Furthermore, insulin receptor blockade with GSK1838705 significantly suppressed the insulin‐induced augmentation in CAP‐activated currents (n = 13) as well as the response magnitude of CAP‐induced action potentials (n = 9). Likewise, the renal SNA response to CAP after intramuscular injection of insulin (n = 8) was significantly (P < 0.05) greater compared to vehicle (n = 9). The findings suggest that insulin potentiates TRPV1 responsiveness to CAP at the DRG and muscle tissue levels, possibly contributing to the augmentation in sympathoexcitation during activities such as physical exercise.
Key points
Evidence suggests insulin centrally activates the sympathetic nervous system, and a chemical stimulus to tissues activates the sympathetic nervous system via thin fibre muscle afferents.
Insulin is reported to modulate putative chemical‐sensitive channels in the dorsal root ganglion neurons of these afferents.
In the present study, it is demonstrated that insulin potentiates the responsiveness of thin fibre afferents to capsaicin at muscle tissue levels as well as at the level of dorsal root ganglion neurons. In addition, it is demonstrated that insulin augments the sympathetic nerve activity response to capsaicin in vivo.
These data suggest that sympathoexcitation is peripherally mediated via insulin‐induced chemical sensitization.
The present study proposes a possible physiological role of insulin in the regulation of chemical sensitivity in somatosensory thin fibre muscle afferents.
figure legend: Insulin‐induced enhancement of sympathetic nerve activity via sensitization of transient receptor potential vanilloid 1 (TRPV1) in small dorsal root ganglion (DRG) neurons and thin‐fibre muscle afferents. Insulin increases neural discharge in response to exposure to capsaicin, a TRPV1 agonist, in thin‐fibre afferents at the level of the DRG in vitro and the skeletal muscle axon terminal ex vivo via sensitization of TRPV1. Further, in vivo studies demonstrate that intramuscular injection of insulin augments sympathetic nerve activity and blood pressure responses to intra‐arterial injection of capsaicin. These findings suggest that insulin‐induced sensitization of TRPV1 may contribute to the augmentation in sympathoexcitation during activities such as physical exercise. Design made in BioRender.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>34967443</pmid><doi>10.1113/JP282740</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0003-4455-8084</orcidid><orcidid>https://orcid.org/0000-0003-1048-9543</orcidid><orcidid>https://orcid.org/0000-0002-5554-0659</orcidid><orcidid>https://orcid.org/0000-0002-4866-6536</orcidid><orcidid>https://orcid.org/0000-0002-5853-5193</orcidid><orcidid>https://orcid.org/0000-0002-7531-9388</orcidid><orcidid>https://orcid.org/0000-0001-9450-9171</orcidid><orcidid>https://orcid.org/0000-0002-2143-2342</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-3751 |
| ispartof | The Journal of physiology, 2022-02, Vol.600 (3), p.531-545 |
| issn | 0022-3751 1469-7793 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8810710 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Wiley Online Library Free Content; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Capsaicin Capsaicin - pharmacology Capsaicin receptors chemical sensitization Chemical stimuli Dorsal root ganglia exercise pressor reflex Ganglia, Spinal - physiology group IV muscle afferents hyperinsulinaemia Insulin Insulin - pharmacology Mechanical stimuli Mice Muscle Fibers, Skeletal Nervous system Neurons Neurons - physiology Nociceptors Pain perception primary sensory neuron Rats Rats, Sprague-Dawley Rodentia Sympathetic nerves Sympathetic nervous system transient receptor potential vanilloid 1 TRPV Cation Channels - physiology |
| title | Insulin potentiates the response to capsaicin in dorsal root ganglion neurons in vitro and muscle afferents ex vivo in normal healthy rodents |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-14T09%3A00%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Insulin%20potentiates%20the%20response%20to%20capsaicin%20in%20dorsal%20root%20ganglion%20neurons%20in%20vitro%20and%20muscle%20afferents%20ex%20vivo%20in%20normal%20healthy%20rodents&rft.jtitle=The%20Journal%20of%20physiology&rft.au=Hori,%20Amane&rft.date=2022-02-01&rft.volume=600&rft.issue=3&rft.spage=531&rft.epage=545&rft.pages=531-545&rft.issn=0022-3751&rft.eissn=1469-7793&rft_id=info:doi/10.1113/JP282740&rft_dat=%3Cproquest_pubme%3E2623811745%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2623811745&rft_id=info:pmid/34967443&rfr_iscdi=true |