Effect of agmatine on insulin resistance

Autor: Hsien-Hui Chung, 鍾憲輝
Rok vydání: 2006
Druh dokumentu: 學位論文 ; thesis
Popis: 94
Diabetes mellitus (DM) is a metabolic disease caused by impaired insulin action, and 90% diabetic patients belong to type Π diabetes. Because insulin resistance is a major of type Π diabetes, it is the main target to treat type Π diabetes by improving insulin resistance. Agmatine is the decarboxylation product of amino acid arginine, and it is regarded as a kind of neurotransmitter exerting its effects by binding to imidazoline receptors in vivo. Previous studies showed that agmatine can lower plasma glucose in type Ι diabetic rats by intravenous injection. Also, the glucose-lowering action of agmatine is due to an activation of imidazoline receptors in adrenal gland which leads to the release of β-endorphin to activate opioid receptors. Therefore, the present study was designed to investigate the effect of agmatine on insulin resistance and discuss its possible mechanism. In this experiment, we used animals expressing insulin resistance, including fructose-fed rats and genetically obese Zucker rats. In addition, we investigated the effect of agmatine on insulin resistance by using the methods of hyperinsulinemic euglycemic clamp、glucose tolerance test、HOMA-IR (Homeostasis model assessment- insulin resistance)、and tolbutamide test. At first, we use the clinical HOMA-IR to evaluate insulin resistance. Then, we treated obese Zucker rats with agmatine 1mg/kg three times a day for 14 days by continuous intravenous injections, and drew blood to measure the fasting plasma glucose (mmol/l) and plasma insulin (μU/ml) on the 0th、7th、14th day, respectively. Then, we obtained HOMA-IR index from the two parameters in a formula. As a result, we found that the HOMA-IR index on the 14th day is lower than that on the 0th day, and it showed obvious difference between them (P
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