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

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...

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Bibliographic Details
Published in:	Experimental biology and medicine (Maywood, N.J.) Vol. 228; no. 10; p. 1138
Main Authors:	Nagai, Katsuya, Niijima, Akira, Yamano, Toshihiko, Otani, Hiroto, Okumra, Nobuaki, Tsuruoka, Nobuo, Nakai, Masaaki, Kiso, Yoshinobu
Format:	Journal Article
Language:	English
Published:	England 01-11-2003
Subjects:	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
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Summary:	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.
ISSN:	1535-3702
DOI:	10.1177/153537020322801007