Activation of imidazoline I2B receptors by guanidine to increase glucose uptake in skeletal muscle of rats

Chang, Chin-Hong; Tsao, Chiung–Wen; Huang, Shuping

doi:10.1016/j.neulet.2009.10.026

Cited by 16 publications

(21 citation statements)

References 18 publications

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“…Isolated skeletal muscle preparations are short-lived for experimental manipulation [ 24 ] and are obtained from sacrifi ced animals; therefore, we used C 2 C 12 cells as an alternative to investigate the mechanisms of allantoin-induced glucose uptake. In this cell line, the presence of I 2B R has been demonstrated [ 19 ] . Allantoin increased AMPK phosphorylation to facilitate glucose uptake into C 2 C 12 cells, and this eff ect was blocked by pretreatment with an I 2 R antagonist, indicating the mediation of I 2 R in the allantoin-induced increase of glucose uptake.…”

mentioning

confidence: 78%

“…In the previous study [ 18 ] , an activation of I 2B receptors may increase the glucose uptake into skeletal muscle has been indicated. Recent evidence [ 19 ] has also mentioned that activation of imidazoline I 2B receptor (I 2B R) by guanidine increased glucose uptake; however, the eff ect of allantoin on I 2B R is still unknown. Therefore, in the present study, we identifi ed that allantoin, a guanidinium derivative, might activate I 2B R to facilitate glucose uptake into C 2 C 12 cells via an AMPK-dependent pathway.…”

Section: Affi Liationsmentioning

confidence: 99%

“…2a ) at a dose suffi cient to block I 2 R [ 19 ] . Previous studies have demonstrated that guanidine might activate I 2B R to increase glucose uptake via the AMPK pathway [ 10 ] and facilitate glucose uptake into skeletal muscle [ 19 ] . Consistent with these reports, allantoin signifi cantly increased AMPK phosphorylation ( • ▶ Fig.…”

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confidence: 99%

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Activation of Imidazoline I-2B Receptors by Allantoin to Increase Glucose Uptake into C2C12 Cells

et al. 2012

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Allantoin, an active principle of the yam, belongs to the group of guanidinium derivatives and has been reported to lower plasma glucose in diabetic animals. Recent evidence indicates that activation of the imidazoline I(2B) receptor (I(2B)R) by guanidinium derivatives also increases glucose uptake; however, the effect of allantoin on I(2B)R is still unknown. Glucose uptake into cultured C₂C₁₂ cells was determined using 2-[¹⁴C]-deoxy-D-glucose as a tracer. The changes in 5'-AMP-activated protein kinase (AMPK) expression were also identified by Western blotting analysis. The allantoin-induced glucose uptake action was dose-dependently blocked by BU224, a specific I₂R antagonist, in C₂C₁₂ cells. Moreover, AMPK phosphorylation by allantoin was found to be dose-dependently increased in C₂C₁₂ cells using AICAR treatment as a reference. In addition, both actions of allantoin, the increases in glucose uptake and AMPK phosphorylation, were dose-dependently attenuated by amiloride in C₂C₁₂ cells. Moreover, compound C at concentrations sufficient to inhibit AMPK blocked the allantoin-induced glucose uptake and AMPK phosphorylation. Thus, we suggest that allantoin can activate I(2B)R to increase glucose uptake into cells, and propose I(2B)R as a new target for diabetic therapy.

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confidence: 78%

Section: Affi Liationsmentioning

confidence: 99%

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Activation of Imidazoline I-2B Receptors by Allantoin to Increase Glucose Uptake into C2C12 Cells

et al. 2012

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“…Role of I-2 receptors (I-2R) in the action of allantoin was identifi ed by BU224 at the optimal doses to block I-2R as described previously [ 17 ] . Pretreatment of BU224 for 30 min in STZ-diabetic rats markedly inhibited the allantoin-induced actions including blood glucose-lowering eff ect and β-endorphin release ( • ▶ Fig.…”

Section: Blockade Of I-2 Receptors By Bu224 Reverses the Action Of Almentioning

confidence: 99%

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

et al. 2011

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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. More-over, 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.

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“…In addition, rilmenidine also showed the lipid-lowering action in animal models of metabolic disorders [ 15 , 16 ] . The role of I 2 -imidazoline receptors (I 2 R) has been shown in the regulation of glucose utilization [ 17 ] while allantoin could activate I 2 R to increase glucose uptake [ 18 ] . Expression of I 3 -imidazoline receptors has been demonstrated in the pancreas for release of insulin [ 19 ] .…”

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Stimulatory Effect of Allantoin on Imidazoline I1 Receptors in Animal and Cell Line

et al. 2012

Horm Metab Res

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Allantoin is known as the agonist of imidazoline receptor, especially the I₂ subtype. Effect of allantoin on imidazoline I₁ receptor (I₁R) relating to reduction of blood pressure and its merit in steatosis are still obscure. Also, farnesoid X receptor (FXR) plays an important role in lipid homeostasis related to I₁R activation. Thus, we administered allantoin into high fat diet (HFD)-fed mice showing hypertriglyceridemia and hypercholesterolemia. Allantoin significantly improved hyperlipidemia in HFD mice after 4 weeks of administration. Pretreatment with efaroxan, at a dose sufficient to inhibit I₁R activation, attenuated the action of allantoin. In addition, in cultured HepG2 cells, allantoin increased the expression of farnesoid X receptor (FXR). The allantoin-induced FXR expression was blocked by efaroxan. Similar changes were observed in the expressions of FXR-targeted genes. Otherwise, allantoin also lowered systolic blood pressure (SBP) in HFD mice that can be blocked by efaroxan. Taken together, allantoin has an ability to activate I₁R for improvement of metabolic disorders.

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Activation of imidazoline I2B receptors by guanidine to increase glucose uptake in skeletal muscle of rats

Cited by 16 publications

References 18 publications

Activation of Imidazoline I-2B Receptors by Allantoin to Increase Glucose Uptake into C2C12 Cells

Activation of Imidazoline I-2B Receptors by Allantoin to Increase Glucose Uptake into C2C12 Cells

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

Stimulatory Effect of Allantoin on Imidazoline I1 Receptors in Animal and Cell Line

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