Abstract
Type 2 diabetes mellitus and related metabolic disorders, such as dyslipidemia, present increasing challenges to health worldwide, as a result of urbanization, the increasing prevalence of obesity, poor lifestyle, and other stress-related factors. Ishige okamurae extract (IOE) is known to be effective at lowering blood glucose and ameliorating metabolic disease. However, detailed mechanisms for these effects have yet to be elucidated. Here, we show that IOE ameliorates substrate (IRS)/ phosphatidylinositol 3-kinase (PI3K)/Akt pathway and increasing glucose transporter 4 (GLUT4) expression in skeletal muscle and white adipose tissue (WAT). We also demonstrate that IOE increases the expression of fibroblast growth factor (FGF)21, a regulator of glucose and energy metabolism in muscle and WAT. In addition, IOE administration increased peroxisome proliferator-activated receptor γ coactivator 1α expression, which regulates expression of the key thermogenic molecule uncoupling protein 1 in WAT. Thus, the effects of IOE to ameliorate hyperglycemia and adiposity may be mediated through FGF21 activating insulin signaling and increasing the expression of GLUT4 and pro-thermogenic factors.
Highlights
Type 2 diabetes is characterized by insulin resistance and hyperglycemia and is predisposed to by a number of factors, including obesity, inappropriate lifestyle, poor diet, and genetic factors [1,2].Insulin resistance develops as a result of high circulating concentrations of fatty acids and their ectopic deposition in tissues, leading to lower glucose uptake into skeletal muscle [3,4]
We showed that Ishige okamurae extract (IOE) treatment has similar effects to metformin to ameliorate insulin resistance, glucose intolerance, and dyslipidemia in mice, probably through ameliorate insulin resistance, glucose intolerance, and dyslipidemia in mice, probably through
We showed that IOE treatment has similar effects to metformin to ameliorate insulin resistance, glucose intolerance, and dyslipidemia in mice, probably through activation of the insulin signaling pathway and upregulation of glucose transporter 4 (GLUT4) expression
Summary
Type 2 diabetes is characterized by insulin resistance and hyperglycemia and is predisposed to by a number of factors, including obesity, inappropriate lifestyle, poor diet, and genetic factors [1,2].Insulin resistance develops as a result of high circulating concentrations of fatty acids and their ectopic deposition in tissues, leading to lower glucose uptake into skeletal muscle [3,4]. Type 2 diabetes is characterized by insulin resistance and hyperglycemia and is predisposed to by a number of factors, including obesity, inappropriate lifestyle, poor diet, and genetic factors [1,2]. The C57BlKsJ-db/db mouse (db/db mouse) is characterized by hyperglycemia and has been widely used as a model of type 2 diabetes and diabetic nephropathy. The db/db mouse is a model of obesity-induced type 2 diabetes, because it demonstrates very high fat mass due to a mutation in its leptin receptor. Obesity is a significant risk factor for type 2 diabetes because it is associated with insulin resistance [5]. Weight loss can be effective at slowing or preventing the onset of type 2 diabetes
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