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

Lin, Kao‐Chang; Yeh, Lee‐Ren; Chen, L.-J.; Wen, Ya Ju; Cheng, Kai‐Chun; Cheng, Juei Tang

doi:10.1055/s-0031-1295439

Cited by 24 publications

(20 citation statements)

References 22 publications

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“…Allantoin can activate I-1R in brain to produce antihypertension [47] and decrease feeding behaviors [48]. Allantoin can stimulate I-2R to lower blood sugar and improve insulin sensitivity in type 1-like diabetic rats [39][40][41][42]. In this study, allantoin activates I-3R to increase insulin secretion.…”

Section: Discussionmentioning

confidence: 65%

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Allantoin activates imidazoline I-3 receptors to enhance insulin secretion in pancreatic β-cells

et al. 2014

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Background: Imidazoline I 3 receptors (I-3R) can regulate insulin secretion in pancreatic β-cells. It has been indicated that allantoin ameliorates hyperglycemia by activating imidazoline I 2 receptors (I-2R). Thus, the effect of allantoin on I-3R is identified in the present study. Methods: We used male Wistar rats to screen allantoin's ability for lowering of blood glucose and stimulation of insulin secretion. Chinese hamster ovary-K1 cells transfected with imidazoline receptors (NISCH-CHO-K1 cells) were also applied to characterize the direct effect of allantoin on this receptor. Additionally, KU14R as specific antagonist was treated to block I-3R in rats and in the cultured pancreatic β-cells named Min 6 cells. Results: In rats, allantoin decreased blood sugar with an increase in plasma insulin. Also, allantoin enhanced calcium influx into NISCH-CHO-K1 cells in a way similar to agmatine, an I-R agonist. Moreover, KU14R dose-dependently blocked allantoin-induced insulin secretion both in Min 6 cells and in Wistar rats. Conclusion: Allantoin can activate I-3R to enhance insulin secretion for lowering of blood sugar in Wistar rats. Thus, allantoin may provide beneficial effects as a supplement for diabetic patients after clinical trials.

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Section: Discussionmentioning

confidence: 65%

“…These results show that CHO -cells transfected with imidazoline receptor gene can be used to identify the direct effect of allantoin. Allantoin can activate I-2R to lower blood sugar and to improve insulin sensitivity [39][40][41][42]. However, these results were observed in the absence of endogenous insulin.…”

Section: Discussionmentioning

confidence: 98%

Allantoin activates imidazoline I-3 receptors to enhance insulin secretion in pancreatic β-cells

et al. 2014

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“…Allantoin is the main active compound in yam and has been reported to have antidiabetic effects with plasma glucose-lowing action and glucose uptake-enhancing action in muscle tissue [11,18,40]. Under diabetic conditions including insulin resistance, hyperglycemia is a risk factor for age-related loss of muscle mass in sarcopenia, which induces muscle synthesis reduction, chronic inflammation, and mitochondrial dysfunction [41].…”

Section: Discussionmentioning

confidence: 99%

Effects of Rhizome Extract of <em>Dioscorea Batatas </em>and Its Active Compound, Allantoin, on the Regulation of Myoblast Differentiation and Mitochondrial Biogenesis in C2C12 Myotubes

Nan¹,

Kang²,

Park³

et al. 2018

Preprint

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The present study was conducted to investigate the effects of rhizome extract of Dioscorea batatas (Dioscoreae Rhizoma, Chinese Yam) and its bioactive compound, allantoin, on myoblast differentiation and mitochondrial biogenesis in skeletal muscle cells. Yams were extracted in water and the extract was analyzed by HPLC. The expression of C2C12 myotubes differentiation and mitochondrial biogenesis regulators were determined by reverse transcriptase (RT)-PCR or Western blot. The glucose levels and total ATP contents were determined by glucose consumption, glucose uptake and ATP assays, respectively.

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“…3a, b ). Thus, action of allantoin in C 2 C 12 cells appears to be mainly induced through I 2B R. In addition, allantoin had an ability to activate imidazoline I-2R in animals while I 2A R is linked to the increase of β-endorphin release and I 2B R is related to other actions including the infl uence on glucose uptake in skeletal muscle [ 26 ] . However, it is still unclear for the affi nity of allantoin to I 2A R and I 2B R. This point shall be clarifi ed in the future.…”

mentioning

confidence: 91%

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

Cited by 24 publications

References 22 publications

Allantoin activates imidazoline I-3 receptors to enhance insulin secretion in pancreatic β-cells

Allantoin activates imidazoline I-3 receptors to enhance insulin secretion in pancreatic β-cells

Effects of Rhizome Extract of <em>Dioscorea Batatas </em>and Its Active Compound, Allantoin, on the Regulation of Myoblast Differentiation and Mitochondrial Biogenesis in C2C12 Myotubes

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

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