scholarly journals Dihydromyricetin Ameliorates Inflammation-Induced Insulin Resistance via Phospholipase C-CaMKK-AMPK Signal Pathway

2021 ◽  
Author(s):  
Lianjie Hou ◽  
Fangyi Jiang ◽  
Bo Huang ◽  
Weijie Zheng ◽  
Yufei Jiang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Phospholipase C ◽  
Therapeutic Strategy ◽  
Public Health Problem ◽  
Signal Pathway ◽  
Target Protein ◽  
Inflammatory Factors ◽  
Oral Glucose ◽  
The Metabolic Syndrome

Abstract Background Metabolic syndrome is associated with obesity, inflammation, and insulin resistance. Patients with metabolic syndrome have a higher risk of turning into type II diabetes and cardiovascular disease. The metabolic syndrome has become an urgent public health problem. Insulin resistance in obesity is the common pathophysiological basis of metabolic syndrome. The insulin resistance is induced by the increasing levels of inflammatory factors during obesity. Therefore, developing a therapeutic strategy for preventing inflammation-induced insulin resistance has great significance for the treatment of metabolic syndrome. Dihydromyricetin, as a bioactive polyphenol, has been used for anti-inflammatory, anti-tumor, and improving insulin sensitivity. However, the target of DHM and the molecular mechanism of DHM in preventing inflammation-induced insulin resistance are still unclear. Methods In this study, we first confirmed the role of dihydromyricetin in inflammation-induced insulin resistance through ELISA, oral glucose tolerance test and glucose uptake test. Then, we demonstrated the pathway of dihydromyricetin ameliorated inflammation-induced insulin resistance by using signal pathway blockers, Ca2 + probes, and immunofluorescence. Finally, we clarified the target protein of dihydromyricetin by using drug affinity responsive target stability (DARTS) assay, qPCR, and western blotting. Results In this study, we first confirmed that dihydromyricetin ameliorated inflammation-induced insulin resistance in vivo and in vitro. Then, we demonstrated that dihydromyricetin ameliorated inflammation-induced insulin resistance by activating Ca2+-CaMKK-AMPK signal pathway. Finally, we clarified that dihydromyricetin activated Ca2+-CaMKK-AMPK signaling pathway by interacting with phospholipase C (PLC), its target protein. Conclusions Our results not only demonstrated that dihydromyricetin ameliorated inflammation-induced insulin resistance via the PLC-CaMKK-AMPK signal pathway but also discovered that the target protein of dihydromyricetin is PLC. Our results provided experimental data for the development of dihydromyricetin as a functional food additive and a new therapeutic strategy for treating or preventing insulin resistance and metabolic syndrome.

scholarly journals Dihydromyricetin Ameliorates Inflammation-induced Insulin Resistance via Phospholipase C-CaMKK-AMPK Signal Pathway

2020 ◽  
Author(s):  
Lianjie Hou ◽  
Fangyi Jiang ◽  
Bo Huang ◽  
Weijie Zheng ◽  
Yufei Jiang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Phospholipase C ◽  
Therapeutic Strategy ◽  
Public Health Problem ◽  
Signal Pathway ◽  
Target Protein ◽  
Inflammatory Factors ◽  
Oral Glucose ◽  
The Metabolic Syndrome

Abstract Background: Metabolic syndrome is associated with obesity, inflammation, and insulin resistance. Patients with metabolic syndrome have a higher risk of turning into type II diabetes and cardiovascular disease. The metabolic syndrome has become an urgent public health problem. Insulin resistance in obesity is the common pathophysiological basis of metabolic syndrome. The insulin resistance is induced by the increasing levels of inflammatory factors during obesity. Therefore, developing a therapeutic strategy for preventing inflammation-induced insulin resistance has great significance for the treatment of metabolic syndrome. Dihydromyricetin, as a bioactive polyphenol, has been used for anti-inflammatory, anti-tumor, and improving insulin sensitivity. However, the target of DHM and the molecular mechanism of DHM in preventing inflammation-induced insulin resistance are still unclear.Methods: In this study, we first confirmed the role of dihydromyricetin in inflammation-induced insulin resistance through ELISA, oral glucose tolerance test and glucose uptake test. Then, we demonstrated the pathway of dihydromyricetin ameliorated inflammation-induced insulin resistance by using signal pathway blockers, Ca2+ probes, and immunofluorescence. Finally, we clarified the target protein of dihydromyricetin by using drug affinity responsive target stability (DARTS) assay, qPCR, and western blotting.Results: In this study, we first confirmed that dihydromyricetin ameliorated inflammation-induced insulin resistance in vivo and in vitro. Then, we demonstrated that dihydromyricetin ameliorated inflammation-induced insulin resistance by activating Ca2+-CaMKK-AMPK signal pathway. Finally, we clarified that dihydromyricetin activated Ca2+-CaMKK-AMPK signaling pathway by interacting with phospholipase C (PLC), its target protein.Conclusions: Our results not only demonstrated that dihydromyricetin ameliorated inflammation-induced insulin resistance via the PLC-CaMKK-AMPK signal pathway but also discovered that the target protein of dihydromyricetin is PLC. Our results provided experimental data for the development of dihydromyricetin as a functional food additive and a new therapeutic strategy for treating or preventing insulin resistance and metabolic syndrome.

scholarly journals Dihydromyricetin Ameliorates Inflammation-Induced Insulin Resistance via Phospholipase C-CaMKK-AMPK Signal Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Lianjie Hou ◽  
Fangyi Jiang ◽  
Bo Huang ◽  
Weijie Zheng ◽  
Yufei Jiang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Phospholipase C ◽  
Public Health Problem ◽  
Signal Pathway ◽  
Target Protein ◽  
Inflammatory Factors ◽  
The Metabolic Syndrome

Patients with metabolic syndrome have a higher risk of type II diabetes and cardiovascular disease. The metabolic syndrome has become an urgent public health problem. Insulin resistance is the common pathophysiological basis of metabolic syndrome. The higher incidence of insulin resistance in obese groups is due to increased levels of inflammatory factors during obesity. Therefore, developing a therapeutic strategy for insulin resistance has great significance for the treatment of the metabolic syndrome. Dihydromyricetin, as a bioactive polyphenol, has been used for anti-inflammatory, antitumor, and improving insulin sensitivity. However, the target of DHM and molecular mechanism of DHM for preventing inflammation-induced insulin resistance is still unclear. In this study, we first confirmed the role of dihydromyricetin in inflammation-induced insulin resistance in vivo and in vitro. Then, we demonstrated that dihydromyricetin resisted inflammation-induced insulin resistance by activating Ca2+-CaMKK-AMPK using signal pathway blockers, Ca2+ probes, and immunofluorescence. Finally, we clarified that dihydromyricetin activated Ca2+-CaMKK-AMPK signaling pathway by interacting with the phospholipase C (PLC), its target protein, using drug affinity responsive target stability (DARTS) assay. Our results not only demonstrated that dihydromyricetin resisted inflammation-induced insulin resistance via the PLC-CaMKK-AMPK signal pathway but also discovered that the target protein of dihydromyricetin is the PLC. Our results provided experimental data for the development of dihydromyricetin as a functional food and new therapeutic strategies for treating or preventing PLC.

scholarly journals Insulin Resistance, the Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease

2005 ◽  
Vol 90 (3) ◽  
pp. 1578-1582 ◽  
Author(s):  
F. Angelico ◽  
M. Del Ben ◽  
R. Conti ◽  
S. Francioso ◽  
K. Feole ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Oral Glucose ◽  
Nonalcoholic Fatty Liver ◽  
Insulin Resistant ◽  
The Metabolic Syndrome

Background/Aims: An association of nonalcoholic fatty liver disease with the insulin-resistant metabolic syndrome has been suggested. The aim of the study was to assess the association of fatty liver to different degrees of insulin resistance and secretion. Methods and Results: The study was performed in 308 alcohol- and virus-negative consecutive patients attending a metabolic clinic, who underwent a complete clinical and biochemical work-up including oral glucose tolerance test and routine liver ultrasonography. Steatosis was graded as absent/mild, moderate, and severe. In nondiabetic subjects, a progressive (P < 0.05) increase in mean homeostasis model of insulin resistance was recorded from the group without steatosis to the groups with mild/moderate and severe steatosis. Severe steatosis was associated with the clustering of the five clinical and biochemical features proposed for the clinical diagnosis of the metabolic syndrome. Subjects with the metabolic syndrome with a more pronounced insulin resistance had a higher prevalence of severe steatosis (P < 0.01) compared with those with homeostasis model of insulin resistance below the median. Conclusions: The findings stress the heterogeneous presentation of patients with the metabolic syndrome when the diagnosis is based on the broad Adult Treatment Panel III clinical criteria and demonstrate that those who are more insulin resistant have a higher prevalence of severe steatosis.

Tesaglitazar, a dual PPARα/γ agonist, ameliorates glucose and lipid intolerance in obese Zucker rats

2005 ◽  
Vol 289 (4) ◽  
pp. R938-R946 ◽  
Author(s):  
Nicholas D. Oakes ◽  
Pia Thalén ◽  
Therese Hultstrand ◽  
Severina Jacinto ◽  
Germán Camejo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Glucose Tolerance ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Therapeutic Effects ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Mass Load ◽  
Obese Zucker Rats

Insulin resistance, impaired glucose tolerance, high circulating levels of free fatty acids (FFA), and postprandial hyperlipidemia are associated with the metabolic syndrome, which has been linked to increased risk of cardiovascular disease. We studied the metabolic responses to an oral glucose/triglyceride (TG) (1.7/2.0 g/kg lean body mass) load in three groups of conscious 7-h fasted Zucker rats: lean healthy controls, obese insulin-resistant/dyslipidemic controls, and obese rats treated with the dual peroxisome proliferator-activated receptor α/γ agonist, tesaglitazar, 3 μmol·kg−1·day−1 for 4 wk. Untreated obese Zucker rats displayed marked insulin resistance, as well as glucose and lipid intolerance in response to the glucose/TG load. The 2-h postload area under the curve values were greater for glucose (+19%), insulin (+849%), FFA (+53%), and TG (+413%) compared with untreated lean controls. Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance. Fasting FFA were not affected, but postprandial FFA suppression was restored to levels seen in lean controls. Mechanisms of tesaglitazar-induced lowering of plasma TG were studied separately using the Triton WR1339 method. In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls. In conclusion, the glucose/lipid tolerance test in obese Zucker rats appears to be a useful model of the metabolic syndrome that can be used to evaluate therapeutic effects on impaired postprandial glucose and lipid metabolism. The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model.

scholarly journals Insulin resistance and obesity in childhood

2008 ◽  
Vol 159 (suppl_1) ◽  
pp. S67-S74 ◽  
Author(s):  
Francesco Chiarelli ◽  
Maria Loredana Marcovecchio
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Childhood Obesity ◽  
Glucose Tolerance ◽  
Children And Adolescents ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
The Metabolic Syndrome

Childhood obesity is a significant health problem that has reached epidemic proportions around the world and is associated with several metabolic and cardiovascular complications. Insulin resistance is a common feature of childhood obesity and is considered to be an important link between adiposity and the associated risk of type 2 diabetes and cardiovascular disease. Insulin resistance is also a key component of the metabolic syndrome, and its prevalence in the paediatric population is increasing, particularly among obese children and adolescents. Several factors are implicated in the pathogenesis of obesity-related insulin resistance, such as increased free fatty acids and many hormones and cytokines released by adipose tissue.Valid and reliable methods are essential to assess the presence and the extent of insulin resistance, the associated risk factors and the effect of pharmacological and lifestyle interventions. The two most common tests to assess insulin resistance are the hyperinsulinemic euglycemic clamp and the frequently sampled i.v. glucose tolerance test utilizing the minimal model. However, both these tests are not easily accomplished, are time consuming, expensive and invasive. Simpler methods to assess insulin resistance based on surrogate markers derived from an oral glucose tolerance test or from fasting insulin and glucose levels have been validated in children and adolescents and widely used.Given the strong association between obesity, insulin resistance and the development of metabolic syndrome and cardiovascular disease, prevention and treatment of childhood obesity appear to be essential to prevent the development of insulin resistance and the associated complications.

scholarly journals Fasting insulin has a stronger association with an adverse cardiometabolic risk profile than insulin resistance: the RISC study

2009 ◽  
Vol 161 (2) ◽  
pp. 223-230 ◽  
Author(s):  
Susanne R de Rooij ◽  
Jacqueline M Dekker ◽  
Michaela Kozakova ◽  
Asimina Mitrakou ◽  
Olle Melander ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Odds Ratio ◽  
Cardiometabolic Risk ◽  
Oral Glucose ◽  
Fasting Insulin ◽  
Men And Women ◽  
The Metabolic Syndrome ◽  
Preclinical Atherosclerosis

ObjectiveFasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis.Design and methodsThe Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) cohort consists of 1326 European non-diabetic, overall healthy men and women aged 30–60 years. We performed standard oral glucose tolerance tests and hyperinsulinemic euglycemic clamps. As a general measure of cardiovascular risk, we assessed the prevalence of the metabolic syndrome in 1177 participants. Carotid artery intima media thickness (IMT) was measured by ultrasound to assess preclinical atherosclerosis.ResultsFasting insulin was correlated with all elements of the metabolic syndrome. Insulin sensitivity (M/I) was correlated with most elements. The odds ratio for the metabolic syndrome of those in the highest quartile of fasting insulin compared with those in the lower quartiles was 5.4 (95% confidence interval (CI) 2.8–10.3, adjusted for insulin sensitivity) in men and 5.1 (2.6–9.9) in women. The odds ratio for metabolic syndrome of those with insulin sensitivity in the lowest quartile of the cohort compared with those in the higher quartiles was 2.4 (95% CI 1.3–4.7, adjusted for fasting insulin) in men and 1.6 (0.8–3.1) in women. Carotid IMT was only statistically significantly associated with fasting insulin in both men and women.ConclusionsFasting insulin, a simple and practical measure, may be a stronger and independent contributor to cardiometabolic risk and atherosclerosis in a healthy population than hyperinsulinemic euglycemic clamp-derived insulin sensitivity.

scholarly journals The significance of adiponectin as a biomarker in metabolic syndrome and/or coronary artery disease

2015 ◽  
Vol 72 (9) ◽  
pp. 779-784 ◽  
Author(s):  
Sanja Stojanovic ◽  
Marina Deljanin-Ilic ◽  
Stevan Ilic ◽  
Dejan Petrovic ◽  
Svetlana Djukic
Keyword(s):  
Insulin Resistance ◽  
Coronary Artery Disease ◽  
Metabolic Syndrome ◽  
Coronary Artery ◽  
Control Group ◽  
Oral Glucose ◽  
Model Assessment ◽  
Anthropometric Parameters ◽  
The Metabolic Syndrome ◽  
Artery Disease

Introduction/Aim. Adiponectin exerts profound protective actions during insulin resistence or prediabetes progression towards more severe clinical entities such as metabolic syndrome and/or cardiovascular disease. Since hypoadiponectinaemia contributes to the pathophysiology of the metabolic syndrome and coronary artery disease the level of circulating adiponectin may be an early marker of cardiovascular events. The aim of this study was to determine the relationships between serum adiponectin levels and parameters of both insulin sensitivity and obesity in patients with the metabolic syndrome and/or coronary artery disease, as well as to assess predictive value of adiponectin serum levels as a biomarker of these entitetis. Methods. The study included 100 patients with metabolic syndrome and/or coronary artery disease with different degree of insulin resistance and healthy, normoglycemic individuals. The control group comprising healthy, normoglycemic individuals was used for comparison. Serum level of adiponectin, fasting glucose, fasting insulinemia Homeostasis Model Assessment of Insulin Resistance (HOMAIR) index and anthropometric parameters were determined in all the subjects. Adiponectin was measured by using the ultrasensitive ELISA method. Insulinemia was measured by the radioimmunoassay (RIA) method. The presence of glycemic disorders was assessed on the basis of oral glucose tolerance test (OGTT). Results. Adiponectin level was inversely correlated with age (? = - 0.015), parameters of both obesity (R = 0.437; p < 0.001) and insulin resistance (R = 0.374; p < 0.01). Decreasing in the level of adiponectin was strongly implicated in the development of insulin resistance. Most importantly, a statistically significant rapid decrease in adiponectin was in the prediabetic stages (p < 0.01). The predictor value of adiponectin was 1,356.32 ? 402.65 ?g/mL. Conclusions. The obtained resultats suggest that adiponectin may be a useful marker in identification of individuals with risk of developing metabolic syndrome and coronary artery disease, as well as a predictor of prediabetes.

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