BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism...BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism involved in this lack of insulin secretion is unclear.The level of vascular endothelial growth factor B(VEGF-B) is significantly increased in T2 D patients.The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation.It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin.As an in vitro model of normal pancreatic β-cells,the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects.AIM To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation.METHODS The MIN6 mouse pancreatic islet β-cell line was used as the model system.By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells,we examined the effects of VEGF-B on insulin secretion,Ca2+ and cyclic adenosine monophosphate(cAMP) levels,and the insulin secretion signaling pathway.RESULTS Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca2+ and cAMP in MIN6 cells.Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1(PLCγ1),phosphatidylinositol 3-kinase(PI3 K),serine/threonine kinase(AKT),and other proteins in the insulin secretion pathway.Upon knockdown of VEGF-B,MIN6 cells exhibited increased insulin secretion and Ca2+ and cAMP levels and upregulated expression of PLCγ1,PI3 K,AKT,and other proteins.CONCLUSION VEGF-B can regulate insulin secretion by modulating the levels of Ca2+ and cAMP.VEGF-B involvement in insulin secretion is related to the expression of PLCγ1,PI3 K,AKT,and other signaling proteins.These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2 D.展开更多
Insulin resistance(IR)is the common pathophysiological basis of many metabolic diseases.IR is characterized by decreased glucose uptake in skeletal muscle and adipose tissue,especially in skeletal muscle.Skeletal musc...Insulin resistance(IR)is the common pathophysiological basis of many metabolic diseases.IR is characterized by decreased glucose uptake in skeletal muscle and adipose tissue,especially in skeletal muscle.Skeletal muscle is the main target tissue of glucose uptake under insulin stimulation.Glucose uptake by skeletal muscle is complex,and it is controlled by many pathways.The PI3K/AKt/GSK-1 signaling pathway is not only the main pathway for insulin signal transduction but also an important mechanism for regulating blood glucose.From the binding of insulin to its receptors on the surface of target cells to the transportation of glucose from extracellular fluid to skeletal muscle,a series of signal transduction processes is completed,any of which potentially affects the physiological effects of insulin and leads to IR.Resistance exercise(RT)can reduce skeletal muscle IR and effectively improve blood glucose control and glycosylated hemoglobin level in patients with type 2 diabetes mellitus(T2DM).However,the exact mechanism by which RT improves skeletal muscle IR remains unclear.Therefore,this paper discusses the above problems by tracking the progress of the literature to deepen the correlation between RT and skeletal muscle insulin sensitivity and provide further evidence for the application of exercise therapy in IR.In conclusion,RT mainly improves insulin sensitivity of skeletal muscle by increasing muscle mass,microvascular blood flow,and glucose transporter-4 expression in skeletal muscle,as well as by reducing lipid accumulation and inflammation in skeletal muscle.Thus,it is potentially useful in the prevention and treatment of T2DM.展开更多
基金Supported by National Natural Science Foundation of China,No.31771284National Natural Science Foundation of China Youth Project,No.31702024+1 种基金Major Basic Research Project of Shandong Provincial Natural Science Foundation,No.ZR2019ZD27Shandong Province Higher Educational Science and Technology Plan Project,No.J17KA258。
文摘BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism involved in this lack of insulin secretion is unclear.The level of vascular endothelial growth factor B(VEGF-B) is significantly increased in T2 D patients.The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation.It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin.As an in vitro model of normal pancreatic β-cells,the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects.AIM To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation.METHODS The MIN6 mouse pancreatic islet β-cell line was used as the model system.By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells,we examined the effects of VEGF-B on insulin secretion,Ca2+ and cyclic adenosine monophosphate(cAMP) levels,and the insulin secretion signaling pathway.RESULTS Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca2+ and cAMP in MIN6 cells.Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1(PLCγ1),phosphatidylinositol 3-kinase(PI3 K),serine/threonine kinase(AKT),and other proteins in the insulin secretion pathway.Upon knockdown of VEGF-B,MIN6 cells exhibited increased insulin secretion and Ca2+ and cAMP levels and upregulated expression of PLCγ1,PI3 K,AKT,and other proteins.CONCLUSION VEGF-B can regulate insulin secretion by modulating the levels of Ca2+ and cAMP.VEGF-B involvement in insulin secretion is related to the expression of PLCγ1,PI3 K,AKT,and other signaling proteins.These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2 D.
基金National Natural Science Foundation of China Youth Project,No.31702024Shandong Province Higher Educational Science and Technology Plan Project,No.J17KA258.
文摘Insulin resistance(IR)is the common pathophysiological basis of many metabolic diseases.IR is characterized by decreased glucose uptake in skeletal muscle and adipose tissue,especially in skeletal muscle.Skeletal muscle is the main target tissue of glucose uptake under insulin stimulation.Glucose uptake by skeletal muscle is complex,and it is controlled by many pathways.The PI3K/AKt/GSK-1 signaling pathway is not only the main pathway for insulin signal transduction but also an important mechanism for regulating blood glucose.From the binding of insulin to its receptors on the surface of target cells to the transportation of glucose from extracellular fluid to skeletal muscle,a series of signal transduction processes is completed,any of which potentially affects the physiological effects of insulin and leads to IR.Resistance exercise(RT)can reduce skeletal muscle IR and effectively improve blood glucose control and glycosylated hemoglobin level in patients with type 2 diabetes mellitus(T2DM).However,the exact mechanism by which RT improves skeletal muscle IR remains unclear.Therefore,this paper discusses the above problems by tracking the progress of the literature to deepen the correlation between RT and skeletal muscle insulin sensitivity and provide further evidence for the application of exercise therapy in IR.In conclusion,RT mainly improves insulin sensitivity of skeletal muscle by increasing muscle mass,microvascular blood flow,and glucose transporter-4 expression in skeletal muscle,as well as by reducing lipid accumulation and inflammation in skeletal muscle.Thus,it is potentially useful in the prevention and treatment of T2DM.