Activation of imidazoline I 2B  receptors is linked with AMP kinase pathway to increase glucose uptake in cultured C 2 C 12  cells

Lui, Tai Ngar; Tsao, Chiung Wen; Huang, Shih Yun; Chang, Chueh; Cheng, Juei Tang

doi:10.1016/j.neulet.2010.03.024

Cited by 25 publications

(33 citation statements)

References 23 publications

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“…To alleviate whole-animal complexities, C2C12, a mouse skeletal muscle cell line, was selected as an in vitro model to identify molecular and cellular targets of ATP10C and then assess its biological role, if any, in insulin signaling and glucose metabolism [16, 17]. …”

Section: Resultsmentioning

confidence: 99%

Transient Silencing of a Type IV P-Type ATPase,Atp10c, Results in Decreased Glucose Uptake in C2C12 Myotubes

Hurst

Minkin

Biggerstaff

et al. 2012

Journal of Nutrition and Metabolism

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Atp10c is a strong candidate gene for diet-induced obesity and type 2 diabetes. To identify molecular and cellular targets of ATP10C, Atp10c expression was altered in vitro in C2C12 skeletal muscle myotubes by transient transfection with an Atp10c-specific siRNA. Glucose uptake assays revealed that insulin stimulation caused a significant 2.54-fold decrease in 2-deoxyglucose uptake in transfected cells coupled with a significant upregulation of native mitogen-activated protein kinases (MAPKs), p38, and p44/42. Additionally, glucose transporter-1 (GLUT1) was significantly upregulated; no changes in glucose transporter-4 (GLUT4) expression were observed. The involvement of MAPKs was confirmed using the specific inhibitor SB203580, which downregulated the expression of native and phosphorylated MAPK proteins in transfected cells without any changes in insulin-stimulated glucose uptake. Results indicate that Atp10c regulates glucose metabolism, at least in part via the MAPK pathway, and, thus, plays a significant role in the development of insulin resistance and type 2 diabetes.

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Section: Resultsmentioning

confidence: 99%

Transient Silencing of a Type IV P-Type ATPase,Atp10c, Results in Decreased Glucose Uptake in C2C12 Myotubes

Hurst

Minkin

Biggerstaff

et al. 2012

Journal of Nutrition and Metabolism

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“…Administration of the I-1 R agonist, rilmenidine, to a unique animal model of obese spontaneously-hypertensive rats (Koletsky rats) signifi cantly improved hypertension [6] . Activation of I-2 R increases plasma β -endorphin level to facilitate the glucose uptake into muscle for improvement of hyperglycemia [7] . I-3 R stimulates insulin secretion from The imidazoline I-1 receptor (I-1 R) agonists are widely used to lower blood pressure, but their eff ects on hyperlipidemia are still obscure.…”

Section: A Novel Mechanism For Decreasing Plasma Lipid Level From Imimentioning

confidence: 99%

A Novel Mechanism for Decreasing Plasma Lipid Level from Imidazoline I-1 Receptor Activation in High Fat Diet-fed Mice

Niu

Cheng

et al. 2011

Horm Metab Res

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The imidazoline I-1 receptor (I-1 R) agonists are widely used to lower blood pressure, but their effects on hyperlipidemia are still obscure. The present study is aimed to evaluate the possible mechanism(s) of I-1 R in the regulation of lipid homeostasis. Farnesoid X receptor (FXR) plays an important role in blood lipid homeostasis; however, the role of FXR in rilmenidine-induced blood lipid lowering action is still unknown. Thus, we administered rilmenidine, a selective agonist of I-1 R, into high fat diet-fed (HFD) mice showing hypertriglyceridemia and hypercholesterolemia. Rilmenidine significantly ameliorated hyperlipidemia in HFD mice after 7 days of administration. Pretreatment with efaroxan, at a dose sufficient to inhibit I-1 R activation, blocked the effects of rilmenidine. Also, in cultured HepG2 cells, rilmenidine dose-dependently induced the expression of farnesoid X receptor (FXR). The rilmenidine-induced FXR expression and FXR-related genes were blocked by efaroxan. However, rilmenidine treatment did not affect the expression of enzymes related to β-oxidation. In conclusion, activation of I-1 R may activate FXR to lower plasma lipids, suggesting I-1 R as a new target for the treatment of hyperlipidemia.

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“…In recent, 3 subtypes of imidazoline receptors have been proposed; activation of I-1 receptors regulates the blood pressure through central nervous system [4], whereas I-3 receptors participate in insulin release [5] and activation of I-2 receptors (I-2R) increases glucose uptake into muscle cells [6, 7]. The clinical used antihypertensive agent rilmenidine may reduce blood pressure via an activation of imidazoline I 1 -receptors in brain to lower sympathetic tone [8, 9].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Imidazoline Receptors in Blood Vessels for the Development of Antihypertensive Agents

Chen

Tsai

Chen

et al. 2014

BioMed Research International

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It has been indicated that activation of peripheral imidazoline I2-receptor (I-2R) may reduce the blood pressure in spontaneously hypertensive rats (SHRs). Also, guanidinium derivatives show the ability to activate imidazoline receptors. Thus, it is of special interest to characterize the I-2R using guanidinium derivatives in blood vessels for development of antihypertensive agent(s). Six guanidinium derivatives including agmatine, amiloride, aminoguanidine, allantoin, canavanine, and metformin were applied in this study. Western blot analysis was used for detecting the expression of imidazoline receptor in tissues of Wistar rats. The isometric tension of aortic rings isolated from male rats was also estimated. The expression of imidazoline receptor on rat aorta was identified. However, guanidinium derivatives for detection of aortic relaxation were not observed except agmatine and amiloride which induced a marked relaxation in isolated aortic rings precontracted with phenylephrine or KCl. Both relaxations induced by agmatine and amiloride were attenuated by glibenclamide at concentration enough to block ATP-sensitive potassium (KATP) channels. Meanwhile, only agmatine-induced relaxation was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Taken together, we suggest that agmatine can induce vascular relaxation through activation of peripheral imidazoline I2-receptor to open KATP channels. Thus, agmatine-like compound has the potential to develop as a new therapeutic agent for hypertension in the future.

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Activation of imidazoline I 2B receptors is linked with AMP kinase pathway to increase glucose uptake in cultured C 2 C 12 cells

Cited by 25 publications

References 23 publications

Transient Silencing of a Type IV P-Type ATPase,Atp10c, Results in Decreased Glucose Uptake in C2C12 Myotubes

Transient Silencing of a Type IV P-Type ATPase,Atp10c, Results in Decreased Glucose Uptake in C2C12 Myotubes

A Novel Mechanism for Decreasing Plasma Lipid Level from Imidazoline I-1 Receptor Activation in High Fat Diet-fed Mice

Characterization of Imidazoline Receptors in Blood Vessels for the Development of Antihypertensive Agents

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