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

Abstract

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.

Keywords

Sympathetic nerve Parasympathetic nerve Suprachiasmatic nerve Adrenal gland Pancreas Carnosinase 

Abbreviations

BAT

Brown adipose tissue

BP

Blood pressure

BW

Body weight

CAR

l-Carnosine

CN

Carnosinase

2DG

2-Deoxy-d-glucose

DKO

Double knockout

FFA

Free fatty acids

IP

Intraperitoneal

IV

Intravenous

LCV

Lateral cerebral ventricular

MAP

Mean arterial pressure

NK

Natural killer

PEPT1

H+/peptide cotransporter 1

PEPT2

H+/peptide cotransporter 2

PHT1

Peptide/histidine transporter 1

RSNA

Renal sympathetic nerve activity

SCN

Suprachiasmatic nucleus

SGFO

Scent of grapefruit oil

SLVO

Scent of lavender oil

STZ

Streptozotocin

TMN

Tuberomammillary nucleus

UCP

Uncoupling protein

WAT

White adipose tissue

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Katsuya Nagai
    • 1
    • 2
  • 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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