Insulin potentiates the response to mechanical stimuli in small dorsal root ganglion neurons and thin fibre muscle afferents in vitro

Norio Hotta, Kimiaki Katanosaka, Kazue Mizumura, Gary A. Iwamoto, Rie Ishizawa, Han Kyul Kim, Wanpen Vongpatanasin, Jere H. Mitchell, Scott A. Smith, Masaki Mizuno

Research output: Contribution to journalArticle

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Abstract

Key points: Insulin is known to activate the sympathetic nervous system centrally. A mechanical stimulus to tissues activates the sympathetic nervous system via thin fibre afferents. Evidence suggests that insulin modulates putative mechanosensitive channels in the dorsal root ganglion neurons of these afferents. In the present study, we report the novel finding that insulin augments the mechanical responsiveness of thin fibre afferents not only at dorsal root ganglion, but also at muscle tissue levels. Our data suggest that sympathoexcitation is mediated via the insulin-induced mechanical sensitization peripherally. The present study proposes a novel physiological role of insulin in the regulation of mechanical sensitivity in somatosensory thin fibre afferents. Abstract: Insulin activates the sympathetic nervous system, although the mechanism underlying insulin-induced sympathoexcitation remains to be determined. A mechanical stimulus to tissues such as skin and/or skeletal muscle, no matter whether the stimulation is noxious or not, activates the sympathetic nervous system via thin fibre afferents. Evidence suggests that insulin modulates putative mechanosensitive channels in the dorsal root ganglion (DRG) neurons of these afferents. Accordingly, we investigated whether insulin augments whole-cell current responses to mechanical stimuli in small DRG neurons of normal healthy mice. We performed whole-cell patch clamp recordings using cultured DRG neurons and observed mechanically-activated (MA) currents induced by mechanical stimuli applied to the cell surface. Local application of vehicle solution did not change MA currents or mechanical threshold in cultured DRG neurons. Insulin (500 mU mL−1) significantly augmented the amplitude of MA currents (P < 0.05) and decreased the mechanical threshold (P < 0.05). Importantly, pretreatment with the insulin receptor antagonist, GSK1838705, significantly suppressed the insulin-induced potentiation of the mechanical response. We further examined the impact of insulin on thin fibre muscle afferent activity in response to mechanical stimuli in normal healthy rats in vitro. Using a muscle–nerve preparation, we recorded single group IV fibre activity to a ramp-shaped mechanical stimulation. Insulin significantly decreased mechanical threshold (P < 0.05), although it did not significantly increase the response magnitude to the mechanical stimulus. In conclusion, these data suggest that insulin augments the mechanical responsiveness of small DRG neurons and potentially sensitizes group IV afferents to mechanical stimuli at the muscle tissue level, possibly contributing to insulin-induced sympathoexcitation.

Original languageEnglish (US)
Pages (from-to)5049-5062
Number of pages14
JournalJournal of Physiology
Volume597
Issue number20
DOIs
StatePublished - Oct 1 2019

Fingerprint

Spinal Ganglia
Insulin
Neurons
Muscles
Sympathetic Nervous System
Afferent Neurons
In Vitro Techniques
Insulin Antagonists
Architectural Accessibility
Insulin Receptor

Keywords

  • exercise pressor reflex
  • group IV muscle afferents
  • hyperinsulinaemia
  • mechanical sensitization
  • mechano-gated channels
  • primary sensory neuron

ASJC Scopus subject areas

  • Physiology

Cite this

Insulin potentiates the response to mechanical stimuli in small dorsal root ganglion neurons and thin fibre muscle afferents in vitro. / Hotta, Norio; Katanosaka, Kimiaki; Mizumura, Kazue; Iwamoto, Gary A.; Ishizawa, Rie; Kim, Han Kyul; Vongpatanasin, Wanpen; Mitchell, Jere H.; Smith, Scott A.; Mizuno, Masaki.

In: Journal of Physiology, Vol. 597, No. 20, 01.10.2019, p. 5049-5062.

Research output: Contribution to journalArticle

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AU - Katanosaka, Kimiaki

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AU - Iwamoto, Gary A.

AU - Ishizawa, Rie

AU - Kim, Han Kyul

AU - Vongpatanasin, Wanpen

AU - Mitchell, Jere H.

AU - Smith, Scott A.

AU - Mizuno, Masaki

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KW - exercise pressor reflex

KW - group IV muscle afferents

KW - hyperinsulinaemia

KW - mechanical sensitization

KW - mechano-gated channels

KW - primary sensory neuron

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