+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Resistin induces insulin resistance by both AMPK-dependent and AMPK-independent mechanisms in HepG2 cells

Resistin induces insulin resistance by both AMPK-dependent and AMPK-independent mechanisms in HepG2 cells

Endocrine 36(1): 60-69

Resistin is a 12.5-KDa cysteine-rich peptide that has been implicated in the impairment of glucose homeostasis via the AMP-activated protein kinase (AMPK) pathway in a rodent model. However, the role resistin plays in humans is controversial. This study investigated the effect of resistin on glucose metabolism and insulin signaling using human recombinant resistin and small interfering RNA (siRNA) against AMPKalpha2 to treat the human liver HepG2 cells. The mRNA of key genes involved in glucose metabolism and the insulin-signaling pathway were detected by real-time RT-PCR. Phosphorylation levels of Akt and AMPK were measured by western blot. The incorporation of D-[U-(14)C] glucose into glycogen was quantitated by liquid scintillation counting. The results demonstrate that resistin stimulated expressions of glucose-6-phosphatase (G6Pase), phosphoenolypyruvate carboxykinase (PEPCK), and suppressor of cytokine signaling 3 (SOCS-3), repressed the expressions of insulin receptor substrate 2(IRS-2) and glucose transporter 2(GLUT2). In addition, resistin inhibited the insulin-induced phosphorylation of Akt independent of AMPK. In conclusion, our findings suggest that resistin induces insulin resistance in HepG2 cells at least partly via induction of SOCS-3 expression and reduction of Akt phosphorylation through an AMPK-independent mechanism. Resistin also increases glucose production via AMPK-mediated upregulated expression of the genes encoding hepatic gluconeogenic enzymes, G6Pase, and PEPCK.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 055522121

Download citation: RISBibTeXText

PMID: 19440859

DOI: 10.1007/s12020-009-9198-7

Related references

Capsaicin induces apoptosis in human osteosarcoma cells through AMPK-dependent and AMPK-independent signaling pathways. Molecular and Cellular Biochemistry 384(1-2): 229-237, 2013

Metformin suppresses adipogenesis through both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms. Molecular and Cellular Endocrinology 440: 57-68, 2017

AICAR, an AMPK activator, sensitizes TRAIL-mediated apoptosis through p38 MAPK-dependent and AMPK-independent signaling pathways in human bladder cancer T24 cells. European Journal of Cancer 61: S57-S58, 2016

Flavonoids from Tetrastigma obtectum enhancing glucose consumption in insulin-resistance HepG2 cells via activating AMPK. Fitoterapia 90: 240-246, 2013

Discrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPK. Proceedings of the National Academy of Sciences of the United States of America 111(4): E435-E444, 2014

MiR-34a regulates mitochondrial content and fat ectopic deposition induced by resistin through the AMPK/PPARα pathway in HepG2 cells. International Journal of Biochemistry and Cell Biology 94: 133-145, 2018

Casein glycomacropeptide-derived peptide IPPKKNQDKTE ameliorates high glucose-induced insulin resistance in HepG2 cells via activation of AMPK signaling. Molecular Nutrition and Food Research 61(2):, 2017

Piperine regulates glucose metabolism disorder in HepG2 cells of insulin resistance models via targeting upstream target of AMPK signaling pathway. Zhongguo Zhong Yao Za Zhi 42(3): 542-547, 2017

Dose-Dependent AMPK-Dependent and Independent Mechanisms of Berberine and Metformin Inhibition of mTORC1, ERK, DNA Synthesis and Proliferation in Pancreatic Cancer Cells. Plos one 9(12): E114573, 2014

Alpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. Hepatology 48(5): 1477-1486, 2008

Biguanides Exert Antitumoral Actions in Pituitary Tumor Cells Through AMPK-Dependent and -Independent Mechanisms. Journal of Clinical Endocrinology and Metabolism 104(8): 3501-3513, 2019

Hyperosmotic Stress Initiates AMPK-Independent Autophagy and AMPK- and Autophagy-Independent Depletion of Thioredoxin 1 and Glyoxalase 2 in HT22 Nerve Cells. Oxidative Medicine and Cellular Longevity 2019: 2715810, 2019

Restoring diabetes-induced autophagic flux arrest in ischemic/reperfused heart by ADIPOR (adiponectin receptor) activation involves both AMPK-dependent and AMPK-independent signaling. Autophagy 13(11): 1855-1869, 2017

Pioglitazone, a PPARγ agonist, attenuates PDGF-induced vascular smooth muscle cell proliferation through AMPK-dependent and AMPK-independent inhibition of mTOR/p70S6K and ERK signaling. Biochemical Pharmacology 101: 54-70, 2016

AICAR induces phosphorylation of AMPK in an ATM-dependent, LKB1-independent manner. Molecular and Cellular Biochemistry 306(1-2): 239-245, 2007