Possible role of L-carnosine in the regulation of blood glucose through controlling autonomic nerves

Exp Biol Med (Maywood). 2003 Nov;228(10):1138-45. doi: 10.1177/153537020322801007.


Mammalian muscles synthesize L-carnosine, but its roles were unknown. Previously, we found in rats that the administration of a certain amount of L-carnosine elicited an inhibition of the hyperglycemia induced by the injection of 2-deoxy-D-glucose (2DG) into the lateral cerebral ventricle (LCV), and that intravenous injection of L-carnosine inhibited sympathetic nerves and facilitated the parasympathetic nerve. Moreover, the suppressive effect of L-carnosine on the hyperglycemia induced by 2DG was eliminated by thioperamide, a histaminergic H3 receptor. These findings suggested that L-carnosine might control the blood glucose level through regulating autonomic nerves via H3 receptor. To further clarify the function of L-carnosine, we examined its role in the control of the blood glucose. In this experiment, the following results were observed in rats: (i) A certain amount (0.01% or 0.001%) but not a larger amount (0.1%) of L-carnosine given as a diet suppressed the hyperglycemia induced by LCV-injection of 2DG (2DG-hyperglycemia); (ii) LCV-injection but not the injection into the intraperitoneal space (IP) of a certain amount of L-histidine suppressed the 2DG-hyperglycemia; (iii) treatments of diphenhydramine, an H1 antagonist, and alpha-fluoromethylhistidine, an inhibitor of histamine-synthesizing enzyme, reduced the 2DG-hyperglycemia; (iv) the plasma L-carnosine concentration and carnosinase activity showed daily changes; (v) the plasma L-carnosine concentration was significantly lower in the streptozotocin-diabetic rats; (vi) exercise by a running wheel tended to increase carnosine synthase activity in the gastrocnemius muscle and elevated the plasma L-carnosine concentration in the dark (active) period, and enhanced the plasma carnosinase activity in the light period; (vii) IP-injection of certain amount of L-carnosine stimulated the feeding response to IP-injection of 2DG. These findings suggest a possibility that L-carnosine released from muscles due to exercise functions to reduce the blood glucose level through the regulation of the autonomic nerves.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autonomic Pathways / drug effects
  • Autonomic Pathways / metabolism
  • Autonomic Pathways / physiology*
  • Blood Glucose / metabolism*
  • Carnosine / blood
  • Carnosine / metabolism*
  • Carnosine / pharmacology*
  • Deoxyglucose / pharmacology
  • Diabetes Mellitus, Experimental
  • Dipeptidases / metabolism
  • Diphenhydramine / pharmacology
  • Eating / drug effects
  • Eating / physiology
  • Histamine / pharmacology
  • Histidine / pharmacology
  • Histidine Decarboxylase / antagonists & inhibitors
  • Hyperglycemia / chemically induced
  • Hyperglycemia / metabolism
  • Male
  • Methylhistidines / pharmacology
  • Muscles / metabolism
  • Photoperiod
  • Rats
  • Rats, Wistar


  • Blood Glucose
  • Methylhistidines
  • Histidine
  • alpha-fluoromethylhistidine
  • Histamine
  • Diphenhydramine
  • Carnosine
  • Deoxyglucose
  • Dipeptidases
  • aminoacyl-histidine dipeptidase
  • Histidine Decarboxylase