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

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.

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

10.1101/2021.07.27.453999 ◽

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.

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The Effect of Tianmai Xiaoke Pian on Insulin Resistance through PI3-K/AKT Signal Pathway

Journal of Diabetes Research ◽

10.1155/2016/9261259 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Nana Wang ◽

Tiegang Li ◽

Ping Han

Keyword(s):

Insulin Resistance ◽

Fasting Blood Glucose ◽

Area Under The Curve ◽

Diabetic Rats ◽

Signal Pathway ◽

Chromium Picolinate ◽

Oral Glucose ◽

Model Assessment ◽

Insulin Sensitizer ◽

Type 2 Diabetic Mellitus

In the clinical setting, given the potential adverse effects of thiazolidinediones and biguanides, we often have difficulty in treatment that no other insulin sensitizers are available for use in type 2 diabetic mellitus (T2DM) patients. Tianmai Xiaoke Pian (TMXKP) is a traditional Chinese medicine tablet, which is comprised of chromium picolinate, Tianhuafen, Maidong, and Wuweizi. To understand its mechanism of action on insulin resistance, TMXKP (50 mg/kg orally) was tested in T2DM rats (induced by a high-fat diet and streptozotocin). Eight weeks later, fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT) were performed. Area under the curve (AUC) and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated, and PI3-K/AKT signal pathway-related genes and proteins were tested by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis in muscle, adipose, and liver tissues, respectively. TMXKP significantly reduced FBG, OGTT, AUC, and HOMA-IR in diabetic ratsP<0.05. Furthermore, we also observed that TMXKP could significantly decreaseIRS-1,IRS-2,PI3-K p85α, andAKT2gene expression and also IRS-1, IRS-2, PI3-K, AKT2, and p-AKT2 protein expression levelsP<0.05in diabetic rats. These findings confirm that TMXKP can alleviate insulin resistance in T2DM rats through the PI3K/AKT pathway. Thus TMXKP appears to be a promising insulin sensitizer.

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Beta-sitosterol attenuates insulin resistance in adipose tissue via IRS-1/Akt mediated insulin signaling in high fat diet and sucrose induced type-2 diabetic rats

European Journal of Pharmacology ◽

10.1016/j.ejphar.2020.173004 ◽

2020 ◽

Vol 873 ◽

pp. 173004 ◽

Cited By ~ 6

Author(s):

Shyamaladevi Babu ◽

Madhan Krishnan ◽

Ponnulakshmi Rajagopal ◽

Vijayalakshmi Periyasamy ◽

Vishnupriya Veeraraghavan ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Insulin Signaling ◽

High Fat Diet ◽

Diabetic Rats ◽

High Fat ◽

Type 2 Diabetic

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Lycopene Improves Insulin Sensitivity through Inhibition of STAT3/Srebp-1c-Mediated Lipid Accumulation and Inflammation in Mice fed a High-Fat Diet

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0043-101919 ◽

2017 ◽

Vol 125 (09) ◽

pp. 610-617 ◽

Cited By ~ 22

Author(s):

Zhaohui Zeng ◽

Wang He ◽

Zhen Jia ◽

Shu Hao

Keyword(s):

Insulin Resistance ◽

Blood Glucose ◽

Lipid Accumulation ◽

High Fat Diet ◽

Fasting Blood Glucose ◽

Insulin Level ◽

Hepatic Glycogen ◽

High Fat ◽

Beneficial Effects ◽

Stat3 Signaling

AbstractIn the past few years, metabolic disorders, such as type 2 diabetes and metabolic syndrome, have reached global prevalence. Lycopene is one of the major carotenoids in tomatoes, watermelons, red grapefruits, and guava. In the current study, using high fat diet (HFD)-fed mice, we investigated the effect of Lycopene on insulin resistance. We showed that diet containing Lycopene significantly prevented HFD-induced increase of fasting blood glucose and insulin level, glucose and insulin intolerance, and decrease of hepatic glycogen content. We found that Lycopene notably prevented the increase of IL-1β, TNFα and CRP levels in mice fed HFD. We showed that Lycopene improved the lipid profiles in HFD-fed mice, as evidenced by decrease of systemic and hepatic TC, TG and LDL, and increase of HDL. Lycopene suppressed the increase of the expression of Srebp-1c, FAS and ACC-1 in mice fed HFD. The administration of Lycopene notably prevented the expression and phosphorylation of STAT3 in livers of mice induced by HFD. The treatment of adenovirus carrying STAT3 significantly suppressed the decrease of Srebp-1c expression induced by Lycopene. Furthermore, enhancement of STAT3 signaling by adenovirus markedly blocked the reduction of fasting blood glucose and insulin level. In conclusion, in the current study, we found that Lycopene prevented STAT3 signaling and inhibited Srebp-1c and downstream gene expression, resulting in inhibition of lipid accumulation, inflammation, insulin resistance and metabolic dysfunction. Overall, the data in the study provide better understanding of the beneficial effects of Lycopene against insulin resistance and metabolic disorder.

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Alleviative Effect of Alpha-Lipoic Acid on Cognitive Impairment in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.774477 ◽

2021 ◽

Vol 13 ◽

Author(s):

Chih-Yuan Ko ◽

Jian-Hua Xu ◽

Yangming Martin Lo ◽

Rong-Syuan Tu ◽

James Swi-Bea Wu ◽

...

Keyword(s):

Cognitive Impairment ◽

Synaptic Plasticity ◽

Protein Kinase ◽

Lipoic Acid ◽

High Fat Diet ◽

Diabetic Rats ◽

Alpha Lipoic Acid ◽

High Fat ◽

Protein Expressions

Background: The intricate relationship between type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) suggests that insulin is involved in modulating AD-related proteins. Alpha-lipoic acid (ALA) can improve insulin resistance (IR) in diabetic rats. However, the role of ALA in alleviating the cognitive decline of T2DM is not yet clear. This study examined the ameliorative effect of ALA on cognitive impairment, cerebral IR, and synaptic plasticity abnormalities in high-fat diet (HFD) plus streptozotocin (STZ) induced diabetic rats.Methods: The HFD/STZ-induced T2DM male Wistar rats were orally administered with ALA (50, 100, or 200 mg/kg BW) once a day for 13 weeks. Abilities of cognition were measured with a passive avoidance test and Morris water maze. Specimens of blood and brain were collected for biochemical analysis after the rats were sacrificed. Western blotting was used to determine protein expressions in the hippocampus and cortex in the insulin signaling pathways, long-term potentiation (LTP), and synaptic plasticity-related protein expressions.Results: Alpha-lipoic acid improved hyperinsulinemia and the higher levels of free fatty acids of the T2DM rats. Behavioral experiments showed that the administration of ALA improved cognitive impairment in HFD/STZ-induced T2DM rats. ALA ameliorated insulin-related pathway proteins [phosphoinositide 3-kinase (PI3K), phospho-protein kinase B (pAkt)/Akt, and insulin-degrading enzyme (IDE)] and the LTP pathway, as well as synaptic plasticity proteins (calmodulin-dependent protein kinase II, cyclic AMP response element-binding protein, and postsynaptic density protein-95) of the cerebral cortex or hippocampus in HFD/STZ-induced T2DM rats.Conclusion: Our findings suggested that ALA may ameliorate cognition impairment via alleviating cerebral IR improvement and cerebral synaptic plasticity in diabetic rats.

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Effect of polyherbal drug on oxidative stress and insulin resistance in high-fat diet-induced type 2 diabetic rats

All Life ◽

10.1080/26895293.2020.1776772 ◽

2020 ◽

Vol 13 (1) ◽

pp. 310-320

Author(s):

Rahul Gopalakrishnan ◽

Nandhakumar Elumalai ◽

Renuka Alagirisamy

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

High Fat Diet ◽

Diabetic Rats ◽

High Fat ◽

Type 2 Diabetic

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Effects of oat β-glucan, oat resistant starch, and the whole oat flour on insulin resistance, inflammation, and gut microbiota in high-fat-diet-induced type 2 diabetic rats

Journal of Functional Foods ◽

10.1016/j.jff.2020.103939 ◽

2020 ◽

Vol 69 ◽

pp. 103939 ◽

Cited By ~ 1

Author(s):

Yingying Zhu ◽

Lianger Dong ◽

Lu Huang ◽

Zhenxing Shi ◽

Jilin Dong ◽

...

Keyword(s):

Insulin Resistance ◽

Gut Microbiota ◽

Resistant Starch ◽

High Fat Diet ◽

Diabetic Rats ◽

High Fat ◽

Oat Flour ◽

Type 2 Diabetic

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00453.2011 ◽

2012 ◽

Vol 302 (4) ◽

pp. E409-E416 ◽

Cited By ~ 11

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.

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A Possible Mechanism of Metformin in Improving Insulin Resistance in Diabetic Rat Models

International Journal of Endocrinology ◽

10.1155/2019/3248527 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Mengsiyu Li ◽

Xiaowen Hu ◽

Yeqiu Xu ◽

Xiaolin Hu ◽

Chunxue Zhang ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

High Fat Diet ◽

Hepg2 Cells ◽

Diabetic Rats ◽

Enzyme Linked Immunosorbent Assay ◽

Metformin Treatment ◽

High Fat ◽

Rat Models

Background. Type 2 diabetes has become one of the most common diseases worldwide, causing a serious social burden. As a first-line treatment for diabetes, metformin can effectively improve insulin resistance. It has been reported that 12α-hydroxylated BA (mainly CA) is associated with insulin resistance. The purpose of this study was to analyze the changes in CA and possible signaling mechanisms in diabetic rats after metformin intervention. Methods. HepG2 cells were cultured after adding different concentrations of metformin. The cell viability was measured using CCK8 kit, and the expression of FXR, MAFG, and CYP8B1 in cells was detected by WB. The rat models of type 2 diabetes were induced by low-dose streptozotocin by feeding a high-fat diet, and the control rats (CON) were fed on normal food; the diabetic rats (DM) were given a high-fat diet without supplementation with metformin, while the metformin-treated diabetic rats (DM + MET) were given a high-fat diet and supplemented with metformin. Biochemical parameters were detected at the end of the test. Expression levels of FXR, CYP8B1, and MAFG were assessed by WB. Serum CA were measured using an enzyme-linked immunosorbent assay (ELISA). Results. In HepG2 cells, metformin dose-dependently enhanced the transcriptional activity of FXR and MAFG and inhibited the expression of CYP8B1. Metformin-treated DM rats showed improved glucose and bile acid metabolism. In addition, significantly increased FXR and MAFG and decreased CYP8B1 were observed in DM + MET rats. At the same time, the CA content of metformin-treated rats was lower than that of diabetic rats. Conclusion. Changes in CA synthesis after metformin treatment may be associated with inhibition of CYP8B1. These results may play an important role in improving insulin sensitivity after metformin treatment.

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