Effects of resveratrol on the amelioration of insulin resistance in KKAy mice

2012 ◽  
Vol 90 (2) ◽  
pp. 237-242 ◽  
Author(s):  
Sifan Chen ◽  
Jinghua Li ◽  
Zili Zhang ◽  
Wenxue Li ◽  
Yanshuang Sun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Protein Kinase ◽  
Glucose Tolerance ◽  
Serum Insulin ◽  
Underlying Mechanism ◽  
Mrna Levels ◽  
Adipose Tissues ◽  
Adiponectin Mrna

Resveratrol (Res) has attracted great interest regarding its effects related to metabolic syndrome, especially for lipid metabolic disorder or insulin resistance; however, the underlying mechanisms remain elusive. To explore the effects of Res on insulin sensitivity and the underlying mechanism, insulin-resistant KKAy mice were treated with 2 and 4 g/kg diets of Res for 12 weeks. After the treatment, blood glucose, serum insulin, glucose tolerance, and insulin tolerance, as well as other indices such as adiponectin mRNA in epididymal adipose tissues, silent information regulator 1 (Sirt1), AMP-activated protein kinase (AMPK), insulin receptor substrate 1 (IRS1), and phosphorylated protein kinase B (PKB/AKT) proteins in liver and soleus muscles, were investigated. The results indicate that Res intervention reduces blood glucose and serum insulin levels, improves insulin and glucose tolerance, increases serum adiponectin and adiponectin mRNA levels in epididymal adipose tissues, and more importantly, elevates Sirt1, p-AMPK, p-IRS1, and p-AKT levels in liver and soleus muscles. In conclusion, Res could improve insulin sensitivity and ameliorate insulin resistance in KKAy mice, which may be associated with the upregulation of Sirt1 protein in liver and soleus muscles and consequent AMPK activation, as well as insulin-signaling related proteins.

scholarly journals Serum Proinsulin in Bangladeshi Subjects with Impaired Glucose Tolerance

2015 ◽  
Vol 7 (2) ◽  
pp. 41-46
Author(s):  
S Sultana ◽  
Z Zeba ◽  
A Hossain ◽  
A Khaleque ◽  
R Zinnat ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Serum Insulin ◽  
Serum Glucose ◽  
Glucose Load ◽  
Fasting Serum ◽  
Insulin Secretory Capacity ◽  
Proinsulin Level ◽  
Secretory Capacity

Hyperproinsulinemia is commonly present in subjects with impaired glucose tolerance. The present study was undertaken to investigate the proinsulin level in Bangladeshi IGT subjects and to explore its association with insulin resistance. This observational study was conducted under a case-control design with IGT subjects (n=50) and controls (n=44). IGT was diagnosed following the WHO Study Group Criteria. Serum glucose was measured by glucose-oxidase method, serum lipid profile by enzymatic method and serum insulin and serum proinsulin were measured by ELISA method. Insulin secretory capacity (HOMA%B) and insulin sensitivity (HOMA%S) were calculated from fasting serum glucose and fasting serum insulin by homeostasis model assessment. The study subjects were age- and BMI- matched. Mean (±SD) age (yrs) of the control and IGT subjects were 40±6 and 40±5 respectively (p=0.853). Mean (±SD) BMI of the control and IGT subjects were 23±3 and 22±2 respectively (p=0.123). Fasting glucose was not significantly higher in IGT subjects, but serum glucose 2 hours after 75 gm glucose load was significantly higher in IGT subjects. Median (Range) value of fasting serum glucose (mmol/l) of control and IGT subjects were 5.3 (3.8-6) and 5.2 (4-12) respectively; (p=0.297). Median (Range) value of serum glucose (mmol/l) 2 hours after 75 gm glucose load of control and IGT subjects were 6.1 (3-7.8) and 7.9 (5- 21) respectively; (p=0.001). Fasting TG was significantly higher in IGT subjects and LDL-c was significantly lower in IGT subjects. Serum Total cholesterol and HDL-c were not significantly different between the IGT and control subjects. Median (Range) value of fasting serum TG (mg/dl) of control and IGT subjects were 119 (51-474) and 178 (82-540) respectively; (p=0.001). Median (Range) value of fasting serum T chol (mg/dl) of control and IGT subjects were 180 (65-272) and 186 (140-400) respectively; (p=0.191). Median (Range) value of fasting serum HDL-C (mg/dl) of control and IGT subjects were 29 (19-45) and 31 (15-78) respectively; (p=0.914). Median (Range) value of fasting serum LDL-C (mg/dl) of control and IGT subjects were 117(29-201) and 111(41- 320) respectively; (p=0.001). Fasting serum proinsulin was significantly higher in IGT subjects. Median (Range) value of fasting serum proinsulin (pmol/l) of control and IGT subjects were 9.2(1.8-156) and 17(3-51) respectively; (p=0.001). Insulin secretory capacity (HOMA%B) was higher but insulin sensitivity (HOMA%S) was significantly lower in case of IGT subjects. Median (Range) value of HOMA%B of control and IGT subjects were 97(46-498) and 164(17-300) respectively; (p=0.001). Median (Range) value of HOMA%S of control and IGT subjects were 68(19-270) and 39(15-110) respectively (p=0.001). In multiple regression analysis a significant negative association was found between fasting proinsulin and insulin sensitivity (p=0.037). The data led to the following conclusions: a) Insulin resistance is the predominant defect in Bangladeshi IGT subjects. b) Basal proinsulin level is significantly increased in IGT subjects. c) Insulin resistance is negatively associated with serum proinsulin in IGT subjects. DOI: http://dx.doi.org/10.3329/bjmb.v7i2.22411 Bangladesh J Med Biochem 2014; 7(2): 41-46

scholarly journals Hypoglycemic effects and mechanisms of electroacupuncture on insulin resistance

2014 ◽  
Vol 307 (3) ◽  
pp. R332-R339 ◽  
Author(s):  
Jieyun Yin ◽  
Jian Kuang ◽  
Manisha Chandalia ◽  
Demidmaa Tuvdendorj ◽  
Batbayar Tumurbaatar ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Free Fatty Acid ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Postprandial Glucose ◽  
Tolerance Test ◽  
High Fat

The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on blood glucose and insulin sensitivity in mice fed a high-fat diet. Both wild-type (WT) and adipose ectonucleotide pyrophosphate phosphodiesterase (ENPP1) transgenic (TG) mice were fed a high-fat diet for 12 wk; for each mouse, an intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed with or without EA at abdomen or auricular areas. A high-fat diet-induced insulin resistance in both WT and TG mice. In the WT mice, EA at 3 Hz and 15 Hz, but not at 1 Hz or 100 Hz, via CV4+CV12 significantly reduced postprandial glucose levels; EA at 3 Hz was most potent. The glucose level was reduced by 61.7% at 60 min and 74.5% at 120 min with EA at 3 Hz (all P < 0.001 vs. control). Similar hypoglycemic effect was noted in the TG mice. On the contrary, EA at auricular points increased postprandial glucose level ( P < 0.03). 4). EA at 3 Hz via CV4+CV12 significantly enhanced the decrease of blood glucose after insulin injection, suggesting improvement of insulin sensitivity. Plasma free fatty acid was significantly suppressed by 42.5% at 15 min and 50.8% at 30 min with EA ( P < 0.01) in both WT and TG mice. EA improves glucose tolerance in both WT and TG mice fed a high-fat diet, and the effect is associated with stimulation parameters and acupoints and is probably attributed to the reduction of free fatty acid.

scholarly journals Paeoniflorin Ameliorates Fructose-Induced Insulin Resistance and Hepatic Steatosis by Activating LKB1/AMPK and AKT Pathways

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1024 ◽  
Author(s):  
Yu-Cheng Li ◽  
Jing-Yi Qiao ◽  
Bao-Ying Wang ◽  
Ming Bai ◽  
Ji-Duo Shen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Protein Kinase ◽  
Protein Expression ◽  
Hepatic Steatosis ◽  
Coenzyme A ◽  
Serum Insulin ◽  
Regulatory Element ◽  
Fatty Acid Synthetase ◽  
Alcoholic Fatty Liver

The present study aimed to evaluate the effects of paeoniflorin on insulin resistance and hepatic steatosis induced by fructose. Male Sprague-Dawley rats were fed 20% fructose drink for eight weeks. The insulin sensitivity, serum lipid profiles, and hepatic lipids contents were measured. The results showed that paeoniflorin significantly decreased serum insulin and glucagon levels, improved insulin sensitivity and serum lipids profiles, and alleviated hepatic steatosis in fructose-fed rats. Moreover, paeoniflorin enhanced the phosphorylation level of AMP-activated protein kinase (AMPK) and protein kinase B (PKB/AKT) and inhibited the phosphorylation of acetyl coenzyme A carboxylase (ACC)1 in liver. Paeoniflorin also increased the hepatic carnitine palmitoyltransferase (CPT)-1 mRNA and protein expression and decreased the mRNA expression of sterol regulatory element-binding protein (SREBP)1c, stearyl coenzyme A decarboxylase (SCD)-1 and fatty acid synthetase (FAS). Furthermore, we found that paeoniflorin significantly increased the heptatic protein expression of tumor suppressor serine/threonine kinase (LKB)1 but not Ca2+/CaM-dependent protein kinase kinase (CaMKK)β. These results suggest that the protective effects of paeoniflorin might be involved in the activation of LKB1/AMPK and insulin signaling, which resulted in the inhibition of lipogenesis, as well as the activation of β-oxidation and glycogenesis, thus ameliorated the insulin resistance and hepatic steatosis. The present study may provide evidence for the beneficial effects of paeoniflorin in the treatment of insulin resistance and non-alcoholic fatty liver.

scholarly journals Effect of postmenopausal status on insulin sensitivity in myanmar women

2016 ◽  
Vol 7 (5) ◽  
pp. 36-41
Author(s):  
Lwin Aye Thet ◽  
Mya Thanda Sein ◽  
Tint Swe Latt
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Insulin Level ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Insulin Level ◽  
Fasting Serum ◽  
Postmenopausal Status

Background: Animal studies show that ovarian hormone deficiency is associated with development of insulin resistance. In women, the menopause transition marks the cessation of ovarian function and insulin sensitivity would be reduced in postmenopausal women.Aim and Objectives: This study aimed to evaluate the insulin sensitivity in Myanmar postmenopausal women compared to premenopausal womenMaterial and Methods: A cross sectional comparative study was undertaken in non obese, normal glucose tolerant post menopausal women (n=42, BMI (mean± SD) 21.3±2.8 kg/m2, age 52.6±4.4 years) and premenopausal women (n=33, BMI(mean± SD)  19.7±2.2 kg/m2, age32.7±4.9 years). Insulin sensitivity was assessed by homeostasis model assessment method of insulin resistance (HOMA-IR) based on fasting blood glucose and fasting serum insulin level. Blood glucose was determined by glucose oxidase method. Serum insulin was estimated by enzyme linked immunosorbent assay (ELISA).Results:No differences in fasting blood glucose level (Mean ±SD 4.87±0.51 vs. 4.76±0.63mmol/L), fasting serum insulin level [median and interquartile range (IQR) 8.1 (6.7-11.8) vs. 8.1(6.5-9.9)    µ IU/ml] and HOMA-IR [median and IQR 1.7 (1.4-2.8) vs. 1.7 (1.2-2.2)] were found between premenopausal and postmenopausal women.Conclusion: Postmenopausal status has no effect on insulin sensitivity in postmenopausal women.Asian Journal of Medical Sciences Vol.7(5) 2016 36-41

Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulin-resistant mouse models—association with liver and adipose tissue effects

2009 ◽  
Vol 297 (5) ◽  
pp. E1105-E1114 ◽  
Author(s):  
Jing Xu ◽  
Shanaka Stanislaus ◽  
Narumol Chinookoswong ◽  
Yvonne Y. Lau ◽  
Todd Hager ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Hepatic Glucose Production ◽  
Fasting Blood Glucose ◽  
Glucose Turnover ◽  
Rapid Decline ◽  
Adipose Tissues ◽  
Resistant Mouse ◽  
Glucose Lowering

Recombinant fibroblast growth factor (FGF)21 has antihyperglycemic, antihyperlipidemic, and antiobesity effects in diabetic rodent and monkey models. Previous studies were confined to measuring steady-state effects of FGF21 following subchronic or chronic administration. The present study focuses on the kinetics of biological actions of FGF21 following a single injection and on the associated physiological and cellular mechanisms underlying FGF21 actions. We show that FGF21 resulted in rapid decline of blood glucose levels and immediate improvement of glucose tolerance and insulin sensitivity in two animal models of insulin resistance ( ob/ob and DIO mice). In ob/ob mice, FGF21 led to a 40–60% decrease in blood glucose, insulin, and amylin levels within 1 h after injection, and the maximal effects were sustained for more than 6 h despite the 1- to 2-h half-life of FGF21. In DIO mice, FGF21 reduced fasting blood glucose and insulin levels and improved glucose tolerance and insulin sensitivity within 3 h of treatment. The acute improvement of glucose metabolism was associated with a 30% reduction of hepatic glucose production and an increase in peripheral glucose turnover. FGF21 appeared to have no direct effect on ex vivo pancreatic islet insulin or glucagon secretion. However, it rapidly induced typical FGF signaling in liver and adipose tissues and in several hepatoma-derived cell lines and differentiated adipocytes. FGF21 was able to inhibit glucose release from H4IIE hepatoma cells and stimulate glucose uptake in 3T3-L1 adipocytes. We conclude that the acute glucose-lowering and insulin-sensitizing effects of FGF21 are potentially associated with its metabolic actions in liver and adipose tissues.

scholarly journals Deletion of CaMKK2 from the Liver Lowers Blood Glucose and Improves Whole-Body Glucose Tolerance in the Mouse

2012 ◽  
Vol 26 (2) ◽  
pp. 281-291 ◽  
Author(s):  
Kristin A. Anderson ◽  
Fumin Lin ◽  
Thomas J. Ribar ◽  
Robert D. Stevens ◽  
Michael J. Muehlbauer ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Protein Kinase ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
De Novo Lipogenesis ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
Dependent Protein Kinase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dependent Protein

Abstract Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a member of the Ca2+/CaM-dependent protein kinase family that is expressed abundantly in brain. Previous work has revealed that CaMKK2 knockout (CaMKK2 KO) mice eat less due to a central nervous system -signaling defect and are protected from diet-induced obesity, glucose intolerance, and insulin resistance. However, here we show that pair feeding of wild-type mice to match food consumption of CAMKK2 mice slows weight gain but fails to protect from diet-induced glucose intolerance, suggesting that other alterations in CaMKK2 KO mice are responsible for their improved glucose metabolism. CaMKK2 is shown to be expressed in liver and acute, specific reduction of the kinase in the liver of high-fat diet-fed CaMKK2floxed mice results in lowered blood glucose and improved glucose tolerance. Primary hepatocytes isolated from CaMKK2 KO mice produce less glucose and have decreased mRNA encoding peroxisome proliferator-activated receptor γ coactivator 1-α and the gluconeogenic enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, and these mRNA fail to respond specifically to the stimulatory effect of catecholamine in a cell-autonomous manner. The mechanism responsible for suppressed gene induction in CaMKK2 KO hepatocytes may involve diminished phosphorylation of histone deacetylase 5, an event necessary in some contexts for derepression of the peroxisome proliferator-activated receptor γ coactivator 1-α promoter. Hepatocytes from CaMKK2 KO mice also show increased rates of de novo lipogenesis and fat oxidation. The changes in fat metabolism observed correlate with steatotic liver and altered acyl carnitine metabolomic profiles in CaMKK2 KO mice. Collectively, these results are consistent with suppressed catecholamine-induced induction of gluconeogenic gene expression in CaMKK2 KO mice that leads to improved whole-body glucose homeostasis despite the presence of increased hepatic fat content.

scholarly journals Long-term hyperglucagonaemia induces early metabolic and renal phenotypes of Type 2 diabetes in mice

2008 ◽  
Vol 114 (9) ◽  
pp. 591-601 ◽  
Author(s):  
Xiao C. Li ◽  
Tang-dong Liao ◽  
Jia L. Zhuo
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Weight Ratio ◽  
Glomerular Injury ◽  
Glucagon Receptor

Clinical studies have shown that patients with early Type 2 diabetes often have elevated serum glucagon rather than insulin deficiency. Imbalance of insulin and glucagon in favouring the latter may contribute to impaired glucose tolerance, persistent hyperglycaemia, microalbuminuria and glomerular injury. In the present study, we tested the hypothesis that long-term glucagon infusion induces early metabolic and renal phenotypes of Type 2 diabetes in mice by activating glucagon receptors. Five groups of adult male C57BL/6J mice were treated with vehicle, glucagon alone (1 μg/h via an osmotic minipump, intraperitoneally), glucagon plus the glucagon receptor antagonist [Des-His1-Glu9]glucagon (5 μg/h via an osmotic minipump), [Des-His1-Glu9]glucagon alone or a high glucose load alone (2% glucose in the drinking water) for 4 weeks. Glucagon infusion increased serum glucagon by 129% (P<0.05), raised systolic BP (blood pressure) by 21 mmHg (P<0.01), elevated fasting blood glucose by 42% (P<0.01), impaired glucose tolerance (P<0.01), increased the kidney weight/body weight ratio (P<0.05) and 24 h urinary albumin excretion by 108% (P<0.01) and induced glomerular mesangial expansion and extracellular matrix deposition. These responses were associated with marked increases in phosphorylated ERK1/2 (extracellular-signal-regulated kinase 1/2) and Akt signalling proteins in the liver and kidney (P<0.01). Serum insulin did not increase proportionally. Concurrent administration of [Des-His1-Glu9]glucagon with glucagon significantly attenuated glucagon-increased BP, fasting blood glucose, kidney weight/body weight ratio and 24 h urinary albumin excretion. [Des-His1-Glu9]glucagon also improved glucagon-inpaired glucose tolerance, increased serum insulin by 56% (P<0.05) and attenuated glomerular injury. However, [Des-His1-Glu9]glucagon or high glucose administration alone did not elevate fasting blood glucose levels, impair glucose tolerance or induce renal injury. These results demonstrate for the first time that long-term hyperglucagonaemia in mice induces early metabolic and renal phenotypes of Type 2 diabetes by activating glucagon receptors. This supports the idea that glucagon receptor blockade may be beneficial in treating insulin resistance and Type 2 diabetic renal complications.

scholarly journals EVALUATION OF CYCLIC ADENOSINE MONOPHOSPHATE AND NEUROTRANSMITTERS IN EXPERIMENTAL OBESITY: IMPACT OF BLACK PEPPER AND COFFEE AQUEOUS EXTRACTS

2016 ◽  
Vol 9 (9) ◽  
pp. 87 ◽  
Author(s):  
Yasmin Abdel Latif ◽  
Shadia Fathy ◽  
Zakaria El-khayat ◽  
Maha Moustafa ◽  
Abdel Razik Farrag ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Lipid Profile ◽  
High Performance ◽  
Energy Homeostasis ◽  
Body Weight Gain ◽  
Serum Insulin ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Black Pepper

ABSTRACTObjective: This study aims to evaluate the effect of black pepper and coffee extracts on chronic and acute experimental-induced obesity and energyhomeostasis.Methods: Rats were divided into 10 groups including control, high-fat diet (HFD), triton, HFD+triton, black pepper+HFD, black pepper+HFD+triton,coffee+HFD, coffee+HFD+triton, mixture+HFD, and mixture+HFD+triton groups. Blood glucose, serum insulin, and insulin resistance were estimated.Body mass index, food efficiency intake, and body weight gain were calculated. Lipid profile, liver and kidney functions were measured, serum and braincyclic adenosine monophosphate (cAMP) was estimated, and brain neurotransmitters were measured by high-performance liquid chromatography.Furthermore, histopathology of liver was performed.Results: Findings showed that blood glucose, insulin resistance, lipid profile, kidney and liver functions as well as brain cAMP and neurotransmitterswere significantly increased, concomitant with a significant decrease in insulin resistance and serum cAMP in both HFD and triton-induced obesitygroups compared to control.Conclusion: Supplementation with black pepper extract, coffee extract, and a mixture of both significantly improved these findings. In conclusion,black pepper and coffee extracts are overlooked as promising weight reduction and antihyperlipidemic agents.Keywords: Energy homeostasis, Obesity, Black pepper extract, Coffee extract, Cyclic adenosine monophosphate, Neurotransmitters.

scholarly journals Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Denise E. Lackey ◽  
Felipe C. G. Reis ◽  
Roi Isaac ◽  
Rizaldy C. Zapata ◽  
Dalila El Ouarrat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Target Genes ◽  
Obese Mice ◽  
Tissue Macrophage

Abstract Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.

scholarly journals Compound Danshen Dripping Pills Prevented Leptin Deficiency-Induced Hepatic ER Stress, Stimulated Autophagy, and Improved Insulin Resistance of ob/ob Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yanan Shi ◽  
Dan Liu ◽  
Jihong Yuan ◽  
Lihui Yan ◽  
Zhenfeng Zhan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Er Stress ◽  
Heart Diseases ◽  
Fasting Blood Glucose ◽  
Underlying Mechanism ◽  
Hepatic Function ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Signal Sensitivity

Compound Danshen dripping pills (CDDP) is widely used for the treatment of coronary arteriosclerosis and ischemic heart diseases for decades of years. In our study, we interestingly discovered the effects and mechanism of CDDP on insulin resistance that increase the risk factor of cardiovascular diseases. Effects of CDDP on fasting blood glucose, the insulin tolerance test (ITT), the oral glucose tolerance test (OGTT), hepatic function, and underlying mechanism were analyzed in ob/ob mice. CDDP was found improving the impaired insulin signal sensitivity of ob/ob mice by ameliorating insulin and glucose tolerance, improving hepatic phosphorylation of the insulin receptor substrate-1 on Ser 307 (pIRS1) of ob/ob mice, and restoring hepatic function by decreasing serum ALT and AST, which increased in ob/ob mice serum. Decreasing hepatic phosphorylation of pancreatic ER kinase (PERK) and inositol-requiring enzyme-1 (IRE1) regulating hepatic ER stress in the liver of ob/ob mice were increased by CDDP. Furthermore, CDDP was also found stimulating ob/ob mice hepatic autophagy by increasing the expression of Beclin1 and LC3B, while decreasing P62 expression. Our study discovered an important role of CDDP on improving ob/ob mice insulin resistance and liver function probably through relieving hepatic ER stress and stimulating hepatic autophagy, which would broaden the application value and provide more benefits for treating cardiovascular patients. This trial is registered with NCT01659580.

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