scholarly journals   1,25(OH)2D3 attenuates hepatic insulin resistance in rats with streptozotocin -induced diabetes via antioxidation    

2021 ◽  
Author(s):  
GuoYu Huang ◽  
Runrong Ding ◽  
Yujing Zhang ◽  
Jiaojiao Gao ◽  
Wenjie Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Morphological Changes ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Hepatic Insulin Resistance ◽  
Hepatic Glycogen ◽  
Sprague Dawley ◽  
Streptozotocin Induced Diabetes ◽  
Antioxidant Effects

Aim: This study was conducted to explore the mechanism by which 1,25(OH) 2 D 3 ameliorates hepatic insulin resistance in rats with streptozotocin (STZ)-induced type 2 diabetes. Methods: Sprague Dawley (SD) rats were randomly divided into five groups: normal, control, and 1,25(OH) 2 D 3 administered at 0.075, 0.15, and 0.3 μg/kg/d. Tissue and blood samples were obtained from all five groups after 4 and 12 weeks of treatment. Morphological changes in the livers were observed with HE staining. The levels of fasting blood glucose (FBG), insulin, and lipids were determined using an automatic biochemistry analyzer. The levels of hepatic glycogen, superoxide dismutase (SOD), malondialdehyde (MDA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were analyzed by spectrophotometry. Protein expression of AKT and GLUT2 was examined by western blotting. Results: 1,25(OH) 2 D 3 treatment reduced the FBG content as well as hepatic MDA, AST, and ALT levels, improved the activity of SOD, and enhanced the expression of GLUT2 and AKT in diabetic rats. These findings suggest that 1,25(OH) 2 D 3, exerts antioxidant effects and ameliorates insulin resistance in the liver. Conclusion: 1,25(OH) 2 D 3 is a potential agent that could be used in the treatment of insulin resistance in the liver.

scholarly journals The Effect of Sanggua Drink Extract on Insulin Resistance through the PI3K/AKT Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yu Cai ◽  
Ying Wang ◽  
Fei Zhi ◽  
Qi-Chang Xing ◽  
Yun-Zhong Chen
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Hepatic Glycogen ◽  
Insulin Sensitizer ◽  
Radix Puerariae ◽  
Glucose Water ◽  
Protein Expressions

Treating type 2 diabetes mellitus (T2DM) using thiazolidinediones and biguanides can present several challenges for patients. Sanggua Drink (SGD) is a commonly used agent in traditional Chinese medicine, and it consists of Folium Mori, Fructus Momordicae Charantiae, Radix Puerariae Lobatae, and Rhizoma Dioscorea. The hypoglycemic effects and mechanisms of SGD extracts on insulin resistance in diabetic rats were investigated. SGD (1.24 g/kg orally) was verified in T2DM rats induced by a high-fat diet and streptozotocin. The results showed that SGD treatment was observed to reduce fasting blood glucose, water and food intake, total cholesterol triglycerides, and LDL, OGTT, FINS, HOMA-IR, GHb, and MDA and increase hepatic glycogen, HDL, SOD, CAT, and GSH-Px in diabetic rats. Simultaneously, SGD treatment by T2DM showed significantly ameliorated pathological changes and reduced inflammation in the pancreas. Treatment was also observed to increase gene and protein expressions of InsR, IRS-2, PI3K, AKT, and Glut4 in the livers of diabetic treated rats. These results suggest that SGD extracts have hypoglycemic properties and may alleviate insulin resistance in T2DM rats through the PI3K/AKT pathway. Therefore, SGD appears to be a promising insulin sensitizer.

scholarly journals Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated type 2 diabetic rats

2013 ◽  
Vol 218 (3) ◽  
pp. 255-262 ◽  
Author(s):  
C Y Shan ◽  
J H Yang ◽  
Y Kong ◽  
X Y Wang ◽  
M Y Zheng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Intestinal Barrier ◽  
Resistance Index ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Sprague Dawley ◽  
Type 2 Diabetic Patients ◽  
Junction Protein ◽  
Type 2 Diabetic

For centuries, Berberine has been used in the treatment of enteritis in China, and it is also known to have anti-hyperglycemic effects in type 2 diabetic patients. However, as Berberine is insoluble and rarely absorbed in gastrointestinal tract, the mechanism by which it works is unclear. We hypothesized that it may act locally by ameliorating intestinal barrier abnormalities and endotoxemia. A high-fat diet combined with low-dose streptozotocin was used to induce type 2 diabetes in male Sprague Dawley rats. Berberine (100 mg/kg) was administered by lavage to diabetic rats for 2 weeks and saline was given to controls. Hyperinsulinemia and insulin resistance improved in the Berberine group, although there was no significant decrease in blood glucose. Berberine treatment also led to a notable restoration of intestinal villi/mucosa structure and less infiltration of inflammatory cells, along with a decrease in plasma lipopolysaccharide (LPS) level. Tight junction protein zonula occludens 1 (ZO1) was also decreased in diabetic rats but was restored by Berberine treatment. Glutamine-induced glucagon-like peptide 2 (GLP2) secretion from ileal tissue decreased dramatically in the diabetic group but was restored by Berberine treatment. Fasting insulin, insulin resistance index, plasma LPS level, and ZO1 expression were significantly correlated with GLP2 level. In type 2 diabetic rats, Berberine treatment not only augments GLP2 secretion and improves diabetes but is also effective in repairing the damaged intestinal mucosa, restoring intestinal permeability, and improving endotoxemia. Whether these effects are mechanistically related will require further studies, but they certainly support the hypothesis that Berberine acts via modulation of intestinal function.

scholarly journals Cyclosporine-A Attenuates Retinal Inflammation by Inhibiting HMGB-1 Formation in Rats with Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Peng Wang ◽  
Fei Chen ◽  
Xuedong Zhang
Keyword(s):  
Cyclosporine A ◽  
Inflammatory Diseases ◽  
Morphological Changes ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Diabetic Retina ◽  
Tnf Α ◽  
Type 2 Diabetic

Abstract Background:Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy. Methods:Male Sprague-Dawley rats were established to type 2 diabetic model.After 6 weeks, diabetic rats and normal controls were intravitreally injected with Cs-A (42 ng/2 μL) to the left eye, and 2μL DMSO to the right eye for the control. Another part of normal wild-type rats was subjected to intravitreal injections into the left eyes with 5 μL PBS or HMGB-1 (5 ng/5 μL) or HMGB-1(5 ng/5 μL) plus Cs-A (42 ng/2 μL), respectively. Retinal morphological changes were observed with hematoxylin–eosin staining. Expressions of HMGB-1, IL-1β and TNF-α were detected by immunohistochemistry, ELISA or western blot. Results:Retinal expression levels of IL-1β and TNF-α were upregulated in type 2 diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in diabetic retina and relieved the retinopathy in type 2 diabetic rats. Conclusions:Intravitreal administration of Cs-A showed a protective effect on retina of diabetic rats, possibly by downregulating retinal expressions of IL-1β and TNF-α via the suppression of HMGB-1.

scholarly journals Cyclosporine-A Attenuates Retinal Inflammation by Inhibiting HMGB-1 Formation in Rats with Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Peng Wang ◽  
Fei Chen ◽  
Xuedong Zhang
Keyword(s):  
Cyclosporine A ◽  
Inflammatory Diseases ◽  
Morphological Changes ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Diabetic Retina ◽  
Tnf Α ◽  
Type 2 Diabetic

Abstract Background:Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy. Methods:Male Sprague-Dawley rats were established to type 2 diabetic model.After 6 weeks, diabetic rats and normal controls were intravitreally injected with Cs-A (42 ng/2 μL) to the left eye, and 2μL DMSO to the right eye for the control. Another part of normal wild-type rats was subjected to intravitreal injections into the left eyes with 5 μL PBS or HMGB-1 (5 ng/5 μL) or HMGB-1(5 ng/5 μL) plus Cs-A (42 ng/2 μL), respectively. Retinal morphological changes were observed with hematoxylin–eosin staining. Expressions of HMGB-1, IL-1β and TNF-α were detected by immunohistochemistry, ELISA or western blot. Results:Retinal expression levels of IL-1β and TNF-α were upregulated in type 2 diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in diabetic retina and relieved the retinopathy in type 2 diabetic rats. Conclusions:Intravitreal administration of Cs-A showed a protective effect on retina of diabetic rats, possibly by downregulating retinal expressions of IL-1β and TNF-α via the suppression of HMGB-1.

scholarly journals Gynura divaricata ameliorates hepatic insulin resistance by modulating insulin signalling, maintaining glycolipid homeostasis and reducing inflammation in type 2 diabetic mice

2019 ◽  
Vol 8 (6) ◽  
pp. 928-938 ◽  
Author(s):  
Xuan Dong ◽  
Shu-Xiang Zhao ◽  
Bing-Qing Xu ◽  
Yu-Qing Zhang
Keyword(s):  
Insulin Resistance ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Molecular Mechanisms ◽  
Insulin Signalling ◽  
Fasting Blood Glucose ◽  
Hepatic Insulin Resistance ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Insulin Signalling Pathway

Abstract Diabetes mellitus, one of the fastest growing epidemics worldwide, has become a serious health problem in modern society. Gynura divaricata (GD), an edible medicinal plant, has been shown to have hypoglycaemic effects. The molecular mechanisms by which GD improves hepatic insulin resistance (IR) in mice with type 2 diabetes (T2D) remain largely unknown. The aerial parts of GD were prepared in a lyophilized powder, which was added into the diet of T2D mice for 4 weeks. GD could result in an obvious decrease in fasting blood glucose and insulin levels in T2D mice. Meanwhile, the underlying mechanisms involved in the insulin-signalling pathway, glucose metabolism, lipid metabolism and inflammatory reaction in the liver tissue were also investigated by western blot, which indicated that GD further ameliorated hepatic IR by activating the PI3K/p-AKT pathway, decreasing the levels of hepatic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase and increasing the levels of glucokinase and peroxisome proliferator-activated receptor-γ in the livers of T2D mice. GD has the potential to alleviate both hyperglycaemia and hepatic IR in T2D mice. Therefore, GD might be a promising functional food or medicine for T2D treatment.

scholarly journals Cyclosporine-A Attenuates Retinal Inflammation by Inhibiting HMGB-1 Formation in Rats with Type 2 Diabetes Mellitus

2019 ◽  
Author(s):  
Peng Wang ◽  
Fei Chen ◽  
Xuedong Zhang
Keyword(s):  
Cyclosporine A ◽  
Inflammatory Diseases ◽  
Morphological Changes ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Diabetic Retina ◽  
Tnf Α ◽  
Type 2 Diabetic

Abstract Background:Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy. Methods:Male Sprague-Dawley rats were established to type 2 diabetic model.After 6 weeks, diabetic rats and normal controls were intravitreally injected with Cs-A (42 ng/2 μL) to the left eye, and 2μL DMSO to the right eye for the control. Another part of normal wild-type rats was subjected to intravitreal injections into the left eyes with 5 μL PBS or HMGB-1 (5 ng/5 μL) or HMGB-1(5 ng/5 μL) plus Cs-A (42 ng/2 μL), respectively. Retinal morphological changes were observed with hematoxylin–eosin staining. Expressions of HMGB-1, IL-1β and TNF-α were detected by immunohistochemistry, ELISA or western blot. Results:Retinal expression levels of IL-1β and TNF-α were upregulated in type 2 diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in diabetic retina and relieved the retinopathy in type 2 diabetic rats. Conclusions:Intravitreal administration of Cs-A showed a protective effect on retina of diabetic rats, possibly by downregulating retinal expressions of IL-1β and TNF-α via the suppression of HMGB-1.

scholarly journals Pyrrolidine dithiocarbamate enhances hepatic glycogen synthesis and reduces FoxO1-mediated gene transcription in type 2 diabetic rats

2012 ◽  
Vol 302 (4) ◽  
pp. E409-E416 ◽  
Author(s):  
Tienian Zhu ◽  
Ruijing Zhao ◽  
Lizhong Zhang ◽  
Michel Bernier ◽  
Jiankun Liu
Keyword(s):  
Blood Glucose ◽  
Glycogen Synthesis ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Hepatic Glycogen ◽  
Pyrrolidine Dithiocarbamate ◽  
Glycogen Deposition ◽  
Gsk 3Β ◽  
Type 2 Diabetic

The aim of the present study was to examine the effects of pyrrolidine dithiocarbamate (PDTC) on hepatic glycogen synthesis and FoxO1 transcriptional activity in type 2 diabetic rats and the mechanism underlying these effects. Fasting blood glucose and glycogen deposition, together with expressions of two key genes related to gluconeogenesis, were studied in the liver of rats fed a normal diet (NC), high-fat diet (HFD)-induced insulin-resistant rats made type 2 diabetic by a single intraperitoneal injection of streptozotocin (DM), and a DM with intervention of PDTC (DM + PDTC) for 1 wk. The phosphorylation of Akt, GSK-3β, and FoxO1 was assessed in liver extracts of fasted rats by Western blot, whereas indirect immunofluorescence staining was performed to determine the cellular distribution of FoxO1. The DM rats exhibited obvious increases in fasting blood glucose as well as decreased hepatic glycogen content compared with the NC group. Activation of the Akt/GSK-3β pathway and inactivating phosphorylation of FoxO1 were reduced greatly in DM rat livers ( P < 0.01). By contrast, PDTC treatment protected DM rats against high fasting blood glucose and hepatic glycogen deposition loss. PDTC also elicited an increase in Akt/GSK-3β signaling and subsequent inactivation and nuclear export of FoxO1 in DM rat livers, which translated into a significant reduction in the expression of two FoxO1 target genes, phospho enolpyruvate carboxykinase and glucose-6-phosphatase. This study suggests that PDTC enhances hepatic glycogen synthesis, whereas it reduces FoxO1 transcriptional activity in DM rats.

scholarly journals Soluble EGFR, a hepatokine, and adipsin, an adipokine, are biomarkers correlated with distinct aspects of insulin resistance in type 2 diabetes subjects

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Mayu Kyohara ◽  
Jun Shirakawa ◽  
Tomoko Okuyama ◽  
Yu Togashi ◽  
Ryota Inoue ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Growth Factor Receptor ◽  
Hdl Cholesterol ◽  
Insulin Level ◽  
Hepatic Insulin Resistance

Abstract Background Insulin resistance can occur in all metabolic organs including the liver, adipose tissue, and skeletal muscles. Circulating soluble epidermal growth factor receptor (soluble EGFR) and adipsin levels are altered in obese diabetic mice and are possibly correlated with insulin resistance in both mice and humans. Here, we investigated the significance of soluble EGFR and adipsin as biomarkers for insulin resistance in Japanese subjects with type 2 diabetes. Methods We measured the soluble EGFR and adipsin levels in sera from 47 non-diabetic subjects and 106 subjects with type 2 diabetes using enzyme-linked immunosorbent assays (ELISAs) and analyzed the correlations between the soluble EGFR or adipsin levels and metabolic parameters in type 2 diabetes subjects. We also measured the gene expression levels of Egfr and Cfd (adipsin) in the liver, adipose tissue, and skeletal muscle in mice with/without obesity or diabetes. Results The soluble EGFR levels were correlated with the fasting blood glucose level (P = 0.010), HOMA-IR (P = 0.035), HbA1c level (P = 0.007), HDL-cholesterol level (P = 0.044), and FIB-4 index (P = 0.017) after adjustments for age, sex, and total cholesterol levels. These factors are known to be related to hepatic insulin resistance. The serum adipsin levels were correlated with BMI (P < 0.001), waist circumference (P < 0.001), fasting serum insulin level (P = 0.001), HOMA-IR (P = 0.009), CPR-index (P = 0.045), and FIB-4 index (P = 0.007) after adjustments for age, sex and eGFR levels. Abdominal adiposity leads to the potentiation of these factors. The expression of Egfr was abundant in the liver, while Cfd was predominantly expressed in adipose tissue in mice. Conclusions Soluble EGFR, a hepatokine, is correlated with insulin resistance in the liver, while adipsin, an adipokine, is associated with adipose insulin resistance. Trial registration: UMIN Clinical Trials Registry (www.umin.ac.jp), UMIN000020474. Registered 8 January 2016.

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