Abstract
BackgroundGlucose homeostasis is distorted by defects of the PI3K/AKT and AMPK pathways in insulin-sensitive tissues, allowing the accumulation of glucose in the blood. The purpose of this study was to assess the effects and mechanisms by which ethanol extract of Caulerpa lentillifera (CLE) regulates glucose metabolism in C57BL/KsJ-db/db (db/db) mice.MethodsMice were administered CLE (250 or 500 mg/kg BW) or rosiglitazone (RSG, 10 mg/kg BW) for 6 weeks. Then, oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) were performed, and blood glucose was measured in db/db mice. Levels of insulin and insulin resistance factors in plasma, glycogen content in the liver, and IRS, PI3K, AKT, and GLUT4 expressions in skeletal muscles were measured in db/db mice. Glucose uptake and insulin signaling molecules were measured in L6 myocytes, using fluorometry and Western blotting.ResultsCLE significantly decreased fasting blood glucose, glucose level in OGTT and IPITT, plasma insulin, homeostatic model assessment-insulin resistant (HOMA-IR), TNF-α, IL-6, FFA, TG and TC levels, and hepatic glycogen content in db/db mice. CLE significantly increased the activation of IRS, AKT, PI3K, and GLUT4, which are the key effector molecules of the PI3K/AKT pathway in L6 myocytes and the skeletal muscles of db/db mice. The enhanced glucose uptake by CLE was abolished by treatment with a PI3K inhibitor (LY294002), but not by an AMPK inhibitor (compound C) in L6 myocytes. CLE regulated glucose uptake and homeostasis via the PI3K/AKT pathway in myocytes and db/db mice, respectively.ConclusionOur results suggest that CLE could be a potential candidate for the prevention of diabetes.
Highlights
Glucose homeostasis is distorted by defects of the Phosphatidylinositol 3-kinase (PI3K)/AKT and 5′ adenosine monophosphate-activated protein kinase (AMPK) pathways in insulin-sensitive tissues, allowing the accumulation of glucose in the blood
We previously reported in-vitro anti-diabetic effects of the ethanol extract of C. lentillifera (CLE) [13] and in this paper we report the effects of Caulerpa lentillifera (CLE) on insulin resistance and glucose metabolism in db/db mice, and the efficacy was compared with an oral anti-diabetic agent, rosiglitazone (RSG) [14]
Effect of CLE on fasting blood glucose and the oral glucose and intraperitoneal insulin tolerance tests in db/db mice As shown in Figure 1A, db/db mice showed a continuous increase in blood glucose throughout the experiment
Summary
Glucose homeostasis is distorted by defects of the PI3K/AKT and AMPK pathways in insulin-sensitive tissues, allowing the accumulation of glucose in the blood. Guo et al reported that natural products enhance glucose uptake and decrease insulin resistance by the activation of PI3K/AKT or AMPK in diabetic models [7]. A naturally distributed algae in tropical and subtropical regions, has a grape-like appearance, and is used in salads as a vegetable in Japan, Korea, the Philippines, and other countries in south-east Asia [9]. It has gained popularity in international food markets and the seafood industry because it contains high minerals, dietary fiber, vitamin A, vitamin C, and several essential unsaturated fatty acids [10]. We explored the mechanism by which glucose was metabolized, using L6 myocytes and db/db mice
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