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Horm Metab Res 2012; 44(01): 41-46
DOI: 10.1055/s-0031-1295439
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Plasma Glucose-lowering Action of Allantoin is Induced by Activation of Imidazoline I-2 Receptors in Streptozotocin-induced Diabetic Rats

K.-C. Lin
1   Department of Neurology and Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan
2   Institute of Biotechnology, Southern Taiwan University, Yong Kang, Tainan City, Taiwan
,
L.-R. Yeh
3   Department of Radiology, E-Da Hospital and I-Shou University, Kaohsiung City, Taiwan
,
L.-J. Chen
4   Institute of Basic Medical Sciences and Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
,
Y.-J. Wen
4   Institute of Basic Medical Sciences and Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
,
K.-C. Cheng
5   Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima City, Japan
,
J.-T. Cheng
1   Department of Neurology and Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan
4   Institute of Basic Medical Sciences and Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
6   Institute of Medical Science, College of Health Science, Chang Jung Christian University, Guei-Ren, Tainan City, Taiwan
› Author Affiliations
Further Information

Publication History

received 20 August 2011

accepted 26 October 2011

Publication Date:
06 December 2011 (online)

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Abstract

Allantoin, an active principle of yam, is documented to lower plasma glucose in diabetic rats. However, action mechanisms of allantoin remain obscure. It has been indicated that metformin shows ability to activate imidazoline I-2 receptors (I-2R) to lower blood sugar. Allantoin has also a chemical structure similar to metformin; both belong to guanidinium derivative. Thus, it is of special interest to know the effect of allantoin on I-2R. In the present study, the marked plasma glucose-lowering action of allantoin in streptozotocin-induced type-1 like diabetic rats was blocked by specific I-2R antagonist, BU224, in a dose-dependent manner. Also, the increase of β-endorphin release by allantoin was blocked by BU224 in the same manner. Otherwise, amiloride at the dose sufficient to block I-2AR abolished the allantoin-induced β-endorphin release and inhibited the blood glucose-lowering action of allantoin markedly but not completely. The direct effect of allantoin on glucose uptake in isolated skeletal muscle was also blocked by BU224. Also, the phosphorylation of AMPK in isolated skeletal muscle was raised by allantoin in a concentration-dependent manner. More­over, insulin sensitivity in diabetic rats was markedly increased by allantoin and this action was also blocked by BU224. These results suggest that allantoin has an ability to activate imidazoline I-2R while I-2AR is linked to the increase of β-endorphin release and I-2BR is related to other actions including the influence in skeletal muscle for lowering of blood glucose in type-1 like diabetic rats. Thus, allantoin can be developed to treat diabetic disorders in the future.

Key words

allantoin - amiloride - β-endorphin - diabetes - imidazoline receptor
 

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