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 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.
Nagai
Katsuya
K
Division of Protein Metabolism, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan. k_nagai@protein.osaka-u.ac.jp
Niijima
Akira
A
Yamano
Toshihiko
T
Otani
Hiroto
H
Okumra
Nobuaki
N
Tsuruoka
Nobuo
N
Nakai
Masaaki
M
Kiso
Yoshinobu
Y
D000818:Animals; D017776:Autonomic Pathways / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism*; D002336:Carnosine / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental; D004150:Dipeptidases / Q000378:metabolism; D004155:Diphenhydramine / Q000494:pharmacology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D006639:Histidine / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology; D009132:Muscles / Q000378:metabolism; D017440:Photoperiod; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D008762:Methylhistidines; D006639:Histidine; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D004155:Diphenhydramine; D002336:Carnosine; D003847:Deoxyglucose; D004150:Dipeptidases; C019673:aminoacyl-histidine dipeptidase; D006640:Histidine Decarboxylase