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Diabetes and myricetin.

Glucose transporter subtype 4 (GLUT4) is the insulin-regulated glucose transporter found in adipose tissues and striated muscles that is responsible for insulin-regulated glucose disposal. Insulin induces the distribution of GLUT4 to the plasma membrane, where facilitates the passive diffusion of glucose into the cells. GLUT4 is involved in the pathogenesis of many clinical conditions associated with obesity, intra-abdominal fat accumulation and insulin resistance. Scientists form the Universidad Católica de Chile, Santiago, found that myricetin interacts directly with GLUT4, rather than by a mechanism related to protein-tyrosine kinase and insulin signaling inhibition [6]. The found that myricetin inhibited the uptake of methylglucose by adipocytes.

Epidemiological evidence links diabetes mellitus with osteoporosis, caused by oxidative damage in osteoblasts. A study conducted at the Kyung Hee University, Seoul, found that myricetin reduced 2-deoxy-d-ribose induced damage [1]. The researchers tested the effect of myricetin on osteoblasts exposed to 2-deoxy-d-ribose and found that the phytochemicals increased cell survival and calcium deposition and reduced advanced oxidation protein products. This study suggested that myricetin may be a useful dietary supplement for minimizing oxidative injury in diabetes related bone diseases.

Liu and coworkers of the Tajen University, Taiwan, investigated the influence of myricetin and insulin resistance [2]. They conducted an experiment with rats which were fed with a fructose rich diet and were intravenously injected with myricetin for 14 weeks. The found that the phytochemical significantly decreased the high glucose and triglyceride levels in plasma and also significantly increased insulin sensitivity. Myricetin acted by enhancing the insulin action on insulin receptor substrate-1 associated phosphatidylinositol 3-kinase and GLUT4 activity. In another study Liu and coworkers came to the same conclusion [3]. For this study the scientists tested the effect of myricetin, extracted from Abelmoschus moschatus (Malvaceae) on obese Zucker rats. A dose-dependent decrease in the plasma glucose concentration was observed following an injection with the extract. Repeated injection of myricetin (1 mg/kg) during 1 week reduced the value of the glucose-insulin index.

Two Taiwanese studies investigated the effect of myricetin on glucose levels in streptozotocin-induced diabetic rats. The first study found a dose-dependent decrease in glucose level and an increase in plasma beta-endorphin-like immunoreactivity, after injection with myricetin [4]. The glucose-lowering action of myricetin was mediated by activation of opioid mu-receptors of peripheral tissues in response to increased beta-endorphin secretion. Also the second study concluded that myricetin has an ability to enhance glucose utilization to lower plasma glucose in diabetic rats lacking insulin [5]. The researchers used for this study a myricetin extract obtained from the aerial parts of the plant Abelmoschus moschatus. They found that an injection with myricetin decreased the plasma glucose concentration in a dose-dependent manner. The increased glucose uptake was characterized by enhanced of glycogen synthesis in isolated hepatocytes. These results suggest that myricetin has an ability to enhance glucose utilization to lower plasma glucose in diabetic rats lacking insulin.

[1] Myricetin, a naturally occurring flavonoid, prevents 2-deoxy-D-ribose induced dysfunction and oxidative damage in osteoblastic MC3T3-E1 cells. Eur J Pharmacol. 2008 Sep 4;591(1-3):1-6. [2] Myricetin, a naturally occurring flavonol, ameliorates insulin resistance induced by a high-fructose diet in rats. Life Sci. 2007 Nov 10;81(21-22):1479-88.
[3] Improvement of insulin sensitivity in obese Zucker rats by myricetin extracted from Abelmoschus moschatus. Planta Med. 2007 Aug;73(10):1054-60.
[4] Mediation of beta-endorphin by myricetin to lower plasma glucose in streptozotocin-induced diabetic rats. J Ethnopharmacol. 2006 Mar 8;104(1-2):199-206.
[5] Myricetin as the active principle of Abelmoschus moschatus to lower plasma glucose in streptozotocin-induced diabetic rats. Planta Med. 2005 Jul;71(7):617-21.
[6] Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes. Biochem J. 2005 Mar 15;386(Pt 3):471-8.

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