scholarly journals Postprandial triglyceride-rich lipoproteins induce hepatic insulin resistance in HepG2 cells independently of their receptor-mediated cellular uptake

2011 ◽  
Vol 343 (1-2) ◽  
pp. 71-78 ◽  
Author(s):  
Tobias Tatarczyk ◽  
Christian Ciardi ◽  
Andreas Niederwanger ◽  
Michael Kranebitter ◽  
Josef R. Patsch ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cellular Uptake ◽  
Hepg2 Cells ◽  
Hepatic Insulin Resistance ◽  
Postprandial Triglyceride

scholarly journals Theaflavins Improve Insulin Sensitivity through Regulating Mitochondrial Biosynthesis in Palmitic Acid-Induced HepG2 Cells

2018 ◽  
Author(s):  
Tuantuan Tong ◽  
Ning Ren ◽  
Jiafan Wu ◽  
Na Guo ◽  
Xiaobo Liu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Palmitic Acid ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Hepatic Insulin Resistance ◽  
Insulin Resistant ◽  
Mitochondrial Dna Copy Number ◽  
Increase Glucose Uptake

Theaflavins, the characteristic and bioactive polyphenols in black tea, possess the potential improvement effects on insulin resistance-associated metabolic abnormalities including obesity and type 2 diebetes. However, the molecular mechanisms of theaflavins improving insulin sensitivity are still not clear. In this study, we investigated the protective effects and mechanisms of theaflavins on palmitic acid-induced insulin resistance in HepG2 cells. Theaflavins could significantly increase glucose uptake of insulin-resistant cells at noncytotoxic doses. This activity was mediated by upregulating the glucose transporter 4 protein expression, increasing the phosphorylation of IRS-1 at Ser307, and reduced the phosphor-Akt (Ser473) level. Moreover, theaflavins were found to enhance mitochondrial DNA copy number through down-regulate the PGC-1β mRNA level and up-regulate PRC mRNA expression in insulin-resistant HepG2 cells. These results indicated that theaflavins could improve free fatty acid-induced hepatic insulin resistance by promoting mitochondrial biogenesis, and were promising functional food and medicines for insulin resistance-related disorders.

The effect of enterolactone on sphingolipid pathway and hepatic insulin resistance development in HepG2 cells

Life Sciences ◽  
2019 ◽  
Vol 217 ◽  
pp. 1-7 ◽  
Author(s):  
Tomasz Charytoniuk ◽  
Nicoletta Iłowska ◽  
Klaudia Berk ◽  
Krzysztof Drygalski ◽  
Adrian Chabowski ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepg2 Cells ◽  
Hepatic Insulin Resistance ◽  
Resistance Development

scholarly journals Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine

2010 ◽  
Vol 299 (5) ◽  
pp. G1068-G1077 ◽  
Author(s):  
Elango Kathirvel ◽  
Kengathevy Morgan ◽  
Ganesh Nandgiri ◽  
Brian C. Sandoval ◽  
Marie A. Caudill ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Liver ◽  
Signaling Pathways ◽  
Hepg2 Cells ◽  
Fasting Glucose ◽  
Hepatic Insulin Resistance ◽  
Nonalcoholic Fatty Liver ◽  
Downstream Signaling ◽  
Insulin Resistant ◽  
Hepatic Fat

Nonalcoholic fatty liver (NAFL) is a common liver disease, associated with insulin resistance. Betaine has been tested as a treatment for NAFL in animal models and in small clinical trials, with mixed results. The present study aims to determine whether betaine treatment would prevent or treat NAFL in mice and to understand how betaine reverses hepatic insulin resistance. Male mice were fed a moderate high-fat diet (mHF) containing 20% of calories from fat for 7 (mHF) or 8 (mHF8) mo without betaine, with betaine (mHFB), or with betaine for the last 6 wk (mHF8B). Control mice were fed standard chow containing 9% of calories from fat for 7 mo (SF) or 8 mo (SF8). HepG2 cells were made insulin resistant and then studied with or without betaine. mHF mice had higher body weight, fasting glucose, insulin, and triglycerides and greater hepatic fat than SF mice. Betaine reduced fasting glucose, insulin, triglycerides, and hepatic fat. In the mHF8B group, betaine treatment significantly improved insulin resistance and hepatic steatosis. Hepatic betaine content significantly decreased in mHF and increased significantly in mHFB. Betaine treatment reversed the inhibition of hepatic insulin signaling in mHF and in insulin-resistant HepG2 cells, including normalization of insulin receptor substrate 1 (IRS1) phosphorylation and of downstream signaling pathways for gluconeogenesis and glycogen synthesis. Betaine treatment prevents and treats fatty liver in a moderate high-dietary-fat model of NAFL in mice. Betaine also reverses hepatic insulin resistance in part by increasing the activation of IRS1, with resultant improvement in downstream signaling pathways.

scholarly journals Berberine improves hepatic insulin resistance by activating the SIRT1/Opa1 pathway: An in vitro and in vivo study

2021 ◽  
Author(s):  
Jia Xu ◽  
Yining Zhang ◽  
Zhiyi Yu ◽  
Yueqi Guan ◽  
Yuqian Lv ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Animal Models ◽  
Hepg2 Cells ◽  
Insulin Signalling ◽  
Morphological Changes ◽  
Mitochondrial Fusion ◽  
Hepatic Insulin Resistance ◽  
Inner Mitochondrial Membrane

Abstract Aim: This study explored whether abnormality in the inner mitochondrial membrane fusion protein optic atrophy 1 (Opa1) causes hepatic insulin resistance and whether berberine (BBR) can prevent hepatic insulin resistance through the SIRT1/Opa1 pathway. Method: High-fat diet (HFD)-fed mice and db/db mice were used as animal models to study hepatic insulin resistance in vivo . Insulin resistance, morphological changes, and mitochondrial injury of the liver were examined to explore the effects of BBR. SIRT1/Opa1 protein expressions were determined to confirm whether the signalling pathway was damaged in the model animals and involved in BBR treatment. A palmitate (PA)-induced hepatocyte insulin resistance model was established in HepG2 cells in vitro . Opa1 silencing and SIRT1 overexpression were induced to verify whether Opa1 abnormality causes hepatocyte insulin resistance and whether SIRT1 could improve this dysfunction. BBR treatment and SIRT1 silencing were employed to prove that BBR can prevent hepatic insulin resistance by activating the SIRT1/Opa1 pathway. Results: We found that Opa1 deficiency caused imbalance in mitochondrial fusion/fission and impaired insulin signalling in the HepG2 cells. SIRT1 and BBR overexpression ameliorated PA-induced insulin resistance, increased Opa1, and improved mitochondrial function. SIRT1 silencing could partly reverse the effects of BBR in the HepG2 cells. SIRT1 and Opa1 were downregulated in the animal models. BBR attenuated hepatic insulin resistance and enhanced SIRT1/Opa1 signalling in the the db/db mice. Conclusion: Opa1 silencing-mediated mitochondrial fusion/fission imbalance could lead to hepatocyte insulin resistance. BBR may improve hepatic insulin resistance by regulating the SIRT1/Opa1 pathway, and thus, it may be used to treat type 2 diabetes.

scholarly journals Sulforaphane Prevents Hepatic Insulin Resistance by Blocking Serine Palmitoyltransferase 3-Mediated Ceramide Biosynthesis

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1185 ◽  
Author(s):  
Wendi Teng ◽  
Yuan Li ◽  
Min Du ◽  
Xingen Lei ◽  
Siyu Xie ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Signaling Pathway ◽  
Glucose Homeostasis ◽  
Hepg2 Cells ◽  
Hepatic Insulin Resistance ◽  
Serine Palmitoyltransferase ◽  
Insulin Resistant ◽  
Ceramide Production

Sulforaphane (SFA), a naturally active isothiocyanate compound from cruciferous vegetables used in clinical trials for cancer treatment, was found to possess potency to alleviate insulin resistance. But its underlying molecular mechanisms are still incompletely understood. In this study, we assessed whether SFA could improve insulin sensitivity and glucose homeostasis both in vitro and in vivo by regulating ceramide production. The effects of SFA on glucose metabolism and expression levels of key proteins in the hepatic insulin signaling pathway were evaluated in insulin-resistant human hepatic carcinoma HepG2 cells. The results showed that SFA dose-dependently increased glucose uptake and intracellular glycogen content by regulating the insulin receptor substrate 1 (IRS-1)/protein kinase B (Akt) signaling pathway in insulin-resistant HepG2 cells. SFA also reduced ceramide contents and downregulated transcription of ceramide-related genes. In addition, knockdown of serine palmitoyltransferase 3 (SPTLC3) in HepG2 cells prevented ceramide accumulation and alleviated insulin resistance. Moreover, SFA treatment improved glucose tolerance and insulin sensitivity, inhibited SPTLC3 expression and hepatic ceramide production and reduced hepatic triglyceride content in vivo. We conclude that SFA recovers glucose homeostasis and improves insulin sensitivity by blocking ceramide biosynthesis through modulating SPTLC3, indicating that SFA may be a potential candidate for prevention and amelioration of hepatic insulin resistance via a ceramide-dependent mechanism.

scholarly journals The Modulatory Action of Vitamin D on the Renin–Angiotensin System and the Determination of Hepatic Insulin Resistance

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2479 ◽  
Author(s):  
Po Sing Leung
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
Hepg2 Cells ◽  
Renin Angiotensin System ◽  
Hepatic Insulin Resistance ◽  
Alcoholic Fatty Liver ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Insulin Resistant ◽  
Glucose Output

Vitamin D deficiency or hypovitaminosis D is associated with increased risks of insulin resistance, type 2 diabetes mellitus (T2DM) and its related non-alcoholic fatty liver disease (NAFLD). Meanwhile, inappropriate over-activation of the renin–angiotensin system (RAS) in the liver leads to the hepatic dysfunction and increased risk of T2DM, such as abnormalities in lipid and glucose metabolism. Our previous findings have shown that calcitriol, an active metabolite of vitamin D, reduces hepatic triglyceride accumulation and glucose output in diabetic db/db mice and human hepatocellular cell HepG2 cells under insulin-resistant conditions. Notwithstanding the existence of this evidence, the protective action of vitamin D in the modulation of overexpressed RAS-induced metabolic abnormalities in the liver under insulin resistance remains to be elusive and investigated. Herein, we have reported the potential interaction between vitamin D and RAS; and its beneficial effects on the expression and function of the RAS components in HepG2 cells and primary hepatocytes under insulin-resistance states. Our study findings suggest that hormonal vitamin D (calcitriol) has modulatory action on the inappropriate upregulation of the hepatic RAS under insulin-resistant conditions. If confirmed, vitamin D supplementation might provide a nutraceutical potential as a cost-effective approach for the management of hepatic metabolic dysfunction as observed in T2DM and related NAFLD.

Liver-Specific Overexpression of NOS1AP Alleviates Hepatic Insulin Resistance in Obese Mice

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1850-P
Author(s):  
CHEN WANG ◽  
KAIDA MU ◽  
TIANXUE ZHAO ◽  
HUI ZHU ◽  
WEIPING JIA
Keyword(s):  
Insulin Resistance ◽  
Hepatic Insulin Resistance ◽  
Obese Mice

1746-P: Obese Youth with Type 1 Diabetes (T1D) Have Worse Hepatic Insulin Resistance (IR) Than Youth with Type 2 Diabetes (T2D)

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1746-P
Author(s):  
PATTARA WIROMRAT ◽  
MELANIE CREE-GREEN ◽  
BRYAN C. BERGMAN ◽  
KALIE L. TOMMERDAHL ◽  
AMY BAUMGARTNER ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Hepatic Insulin Resistance ◽  
Obese Youth
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