Amino Acids

, Volume 43, Issue 1, pp 97–109 | Cite as

Role of l-carnosine in the control of blood glucose, blood pressure, thermogenesis, and lipolysis by autonomic nerves in rats: involvement of the circadian clock and histamine

  • Katsuya NagaiEmail author
  • Mamoru Tanida
  • Akira Niijima
  • Nobuo Tsuruoka
  • Yoshinobu Kiso
  • Yuko Horii
  • Jiao Shen
  • Nobuaki Okumura
Review Article


l-Carnosine (β-alanyl-l-histidine; CAR) is synthesized in mammalian skeletal muscle. Although the physiological roles of CAR have not yet been clarified, there is evidence that the release of CAR from skeletal muscle during physical exercise affects autonomic neurotransmission and physiological functions. In particular, CAR affects the activity of sympathetic and parasympathetic nerves innervating the adrenal glands, liver, kidney, pancreas, stomach, and white and brown adipose tissues, thereby causing changes in blood pressure, blood glucose, appetite, lipolysis, and thermogenesis. CAR-mediated changes in neurotransmission and physiological functions were eliminated by histamine H1 or H3 receptor antagonists (diphenhydramine or thioperamide) and bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN), a master circadian clock. Moreover, a carnosine-degrading enzyme (carnosinase 2) was shown to be localized to histamine neurons in the hypothalamic tuberomammillary nucleus (TMN). Thus, CAR released from skeletal muscle during exercise may be transported into TMN-histamine neurons and hydrolyzed. The resulting l-histidine may subsequently be converted into histamine, which could be responsible for the effects of CAR on neurotransmission and physiological function. Thus, CAR appears to influence hypoglycemic, hypotensive, and lipolytic activity through regulation of autonomic nerves and with the involvement of the SCN and histamine. These findings are reviewed and discussed in the context of other recent reports, including those on carnosine synthetases, carnosinases, and carnosine transport.


Sympathetic nerve Parasympathetic nerve Suprachiasmatic nerve Adrenal gland Pancreas Carnosinase 



Brown adipose tissue


Blood pressure


Body weight








Double knockout


Free fatty acids






Lateral cerebral ventricular


Mean arterial pressure


Natural killer


H+/peptide cotransporter 1


H+/peptide cotransporter 2


Peptide/histidine transporter 1


Renal sympathetic nerve activity


Suprachiasmatic nucleus


Scent of grapefruit oil


Scent of lavender oil




Tuberomammillary nucleus


Uncoupling protein


White adipose tissue



We would like to express our gratitude to the contributors of this research at the Institute for Protein Research, Osaka University, Japan and at ANBAS Corporation, Ltd., Japan.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Katsuya Nagai
    • 1
    • 2
    Email author
  • Mamoru Tanida
    • 1
    • 2
  • Akira Niijima
    • 1
    • 3
  • Nobuo Tsuruoka
    • 4
  • Yoshinobu Kiso
    • 4
  • Yuko Horii
    • 1
    • 2
  • Jiao Shen
    • 1
    • 2
  • Nobuaki Okumura
    • 2
  1. 1.ANBAS CorporationKita-KuJapan
  2. 2.Institute for Protein Research, Osaka UniversitySuitaJapan
  3. 3.Niigata UniversityNiigataJapan
  4. 4.Institute for Health Care ScienceSuntory Wellness LimitedOsakaJapan

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