Morin is a flavonoid contained in guava that is known to reduce hyperglycemia in diabetics. Morin has been demonstrated to increase plasma insulin. However, the mechanism(s) remains unknown. The present study is designed to investigate the effect of morin on the imidazoline receptor (I-R) that regulates insulin secretion. We used Chinese hamster ovary (CHO) cells transfected with an I-R expression construct (NISCH-CHO-K1 cells) to identify the direct effect of morin on the I-R. Moreover, the imidazoline I₃ receptor (I-3R) is known to be present in pancreatic β cells and involved in insulin secretion. Therefore, we applied a specific antagonist (KU14R) to block I-3R in diabetic rats. Additionally, the effect of morin on insulin secretion was characterized in isolated pancreatic islets. Morin decreased blood glucose levels by increasing plasma insulin levels in diabetic rats. In CHO cells expressing an I-R, morin increased calcium influx in a dose-dependent manner. Additionally, KU14R dose-dependently inhibited the morin-induced effects, including hypoglycemia and the increase in insulin secretion and plasma C-peptide levels, in diabetic rats. Furthermore, morin enhanced insulin secretion from isolated pancreatic islets, and this effect was also dose-dependently inhibited by KU14R. Phospholipase C (PLC) is known to couple with the I-R, and a PLC inhibitor dose-dependently attenuated the insulin secretion induced by morin in isolated pancreatic islets. Taken together, these data suggest that morin can activate I-3R to enhance insulin secretion. Therefore, it would be useful to develop morin into a treatment for diabetic disorders.

2014-05-01·Lower urinary tract symptoms4区 · 医学

Urinary Bladder Relaxation through Activation of Imidazoline Receptors Induced by Agmatine is Increased in Diabetic Rats

4区 · 医学

Article

作者: TONG, Yat‐Ching ; TSAI, Tsung‐Chin ; CHEN, I‐Hung ; CHUNG, Hsien‐Hui ; LIN, Chia‐Ho ; CHENG, Juei‐Tang

ABSTRACT:

Objectives:

The effect of agmatine on bladder contractility and the diabetes‐induced alteration of this action were studied in the rat.

Methods:

Bladder strips were isolated from 9‐week‐old streptozotocin (STZ)‐diabetic rats and control Wistar rats. Strips were hung in an organ bath for measurement of isometric tension and pre‐contracted with either 1 µmol/L acetylcholine (ACh) or 50 mmol/L KCl. Dose‐dependent relaxation of the bladder strips was studied by cumulative administration of agmatine 1–100 µmol/L into the organ bath. Effects of specific imidazoline receptor (IR) antagonists on the agmatine‐induced relaxation were studied. Western blotting analysis was used to measure bladder IR, sulphonylurea receptor (SUR) and inwardly rectifying K+ channel subunit 6.2 (Kir 6.2) protein levels.

Results:

Agmatine reduced ACh and KCl pre‐contracted bladder strip tension in a dose‐dependent fashion. Relaxation was significantly increased in STZ‐diabetic rats. The relaxation was inhibited by BU224, a selective I2 IR antagonist; but not by efaroxan (I1 IR antagonist) or KU14R (I3 IR antagonist). Moreover, the agmatine‐induced relaxation was attenuated by glibenclamide (inhibitor of KATP channel) and H‐89 (inhibitor of protein kinase A), but enhanced by 3‐isobutyl‐1‐methylxanthine (IBMX, inhibitor of cyclic AMP phosphodiesterase). Western blotting showed increased expression of bladder IR but not SUR or Kir 6.2 in the STZ‐diabetic rat.

Conclusion:

Agmatine causes rat bladder relaxation by activation of the I2 IR, which opens KATP channels through the cyclic AMP/protein kinase A pathway. Agmatine‐induced bladder relaxation in STZ‐diabetic rats is increased due to a higher expression of IR.

2013-01-01·Lower urinary tract symptoms4区 · 医学

Agmatine Induces Rat Prostate Relaxation through Activation of Peripheral Imidazoline I₂‐Receptors

4区 · 医学

Article

作者: Chung, Hsien-Hui ; Cheng, Juei-Tang ; Lin, Chia-Ho ; Tong, Yat-Ching ; Lee, Liang-Ming ; Chen, I-Hung

Objectives: The effect of agmatine on prostate contractility as well as the roles of imidazoline receptors and potassium channels in this action were studied using isolated Wistar rat prostate tissue.Methods: Rat prostate strips were pre‐contracted with 1 µmol/L phenylephrine or 50 mmol/L KCl. The relaxation response to agmatine (1–100 µmol/L) was measured. The effects of imidazoline receptor blockers: efaroxan, BU224, KU14R; ATP‐sensitive K+ channels (KATP) channel inhibitor: glibenclamide; cyclic AMP (cAMP) phosphodiesterase inhibitor: IBMX; or protein kinase A (PKA) inhibitor: H‐89 on the agmatine‐induced relaxation were studied.Results: Agmatine produced relaxation in prostate strips pre‐contracted with phenylephrine or KCl in a dose‐dependent manner. This relaxation was significantly reduced by BU224, a selective I2 imidazoline receptor (IR) blocker, but not by I1 or I3 IR blockers (efaroxan, KU14R respectively). Moreover, the agmatine‐induced relaxation was attenuated by glibenclamide and H‐89, but enhanced by IBMX.Conclusion: The results suggest that agmatine causes rat prostate relaxation by activation of the I2 IR, which opens KATP channels through cAMP/PKA pathway.

100 项与 KU-14R 相关的药物交易

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