Erratum: FoxO1 integrates direct and indirect effects of insulin on hepatic glucose production and glucose utilization

O-Sullivan, InSug; Zhang, Wenwei; Wasserman, David H.; Liew, Chong Wee; Liu, Jonathan; Paik, Jihye; DePinho, Ronald A.; Stolz, Donna B.; Kahn, C. Ronald; Schwartz, Michael W.; Unterman, Terry G.

doi:10.1038/ncomms8861

Cited by 7 publications

(3 citation statements)

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“…We wondered whether this effect of artemether is associated with altered glucose metabolism in the liver. To test this possibility, we checked the protein expression level of glucokinase (GK) and phosphoenolpyruvate carboxykinase (PEPCK), two critical rate-limiting enzymes individually controlling hepatic glycolysis and gluconeogenesis (17,18), by Western blotting analysis using the liver samples obtained from db/+ mice in the negative control (NC) group and DM group administrated with or without artemether. These db/db mice naturally showed typical diabetic characteristics, like significant changes in food intake, body weight, and fasting blood glucose (FBG), which were dose-dependently reversed to some extent by artemether treatment (Figures 1A-C), as similarly reported by a previous study (14).…”

Section: Artemether Regulates Expression Of Glucose Metabolic Enzymesmentioning

confidence: 99%

Antidiabetic Effect of Artemether in Db/Db Mice Involves Regulation of AMPK and PI3K/Akt Pathways

et al. 2020

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The traditional Chinese medicine has long been used in the treatment of diabetes, one major disease threatening the public health. It has been reported that artemether exerts antidiabetic effects on type 2 diabetes in db/db mice, however the underlying mechanisms remain unknown. In the present study, we show that artemether regulates expression of related enzymes participating in the glucose and lipid metabolism in the liver of db/db mice, which could at least partly explain the improved glucose and lipid metabolism in artemether-treated mice. Additionally, artemether also regulates expression of glycogen synthesis related enzymes in the skeletal muscle of db/db mice, supporting its promotive role in glycogen synthesis. Mechanistically, artemether activates AMPK pathway as well as PI3K/Akt pathway in the liver and skeletal muscle of db/db mice, suggesting that these two signaling pathways are both involved in the antidiabetic effects of artemether on type 2 diabetes in db/db mice. In conclusion, our study connects the antidiabetic effects of artemether to the regulation of metabolic enzymes and signaling pathways, and also provides molecular basis for the potential application of artemether in treating type 2 diabetes.

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Section: Artemether Regulates Expression Of Glucose Metabolic Enzymesmentioning

confidence: 99%

Antidiabetic Effect of Artemether in Db/Db Mice Involves Regulation of AMPK and PI3K/Akt Pathways

et al. 2020

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“…Foxo1 is a putative target of miR-486-5p based on a Targetscan prediction ( 28 , 29 ), with an interaction being reported in the context of kidney disease. Increased hepatic miR-486 expression may also reduce Foxo1, resulting in reduced insulin resistance that may then affect fertility ( 30 ). Furthermore, miR-486-5p was shown to be downregulated in oocytes in polycystic ovarian syndrome (PCOS), which potentially leads to cumulus cell proliferation ( 31 ), but increased levels were associated with endometriosis ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Association of microRNAs With Embryo Development and Fertilization in Women Undergoing Subfertility Treatments: A Pilot Study

Butler¹,

Cunningham²,

Ramachandran³

et al. 2021

Front. Reprod. Health

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Objective: Small non-coding RNAs, known as microRNAs (miRNAs), have emerging regulatory functions within the ovary that have been related to fertility. This study was undertaken to determine if circulating miRNAs reflect the changes associated with the parameters of embryo development and fertilization.Methods: In this cross-sectional pilot study. Plasma miRNAs were collected from 48 sequentially presenting women in the follicular phase prior to commencing in vitro fertilization (IVF). Circulating miRNAs were measured using locked nucleic acid (LNA)-based quantitative PCR (qPCR), while an updated miRNA data set was used to determine their level of expression.Results: Body mass index and weight were associated with the miRNAs let7b-3p and miR-375, respectively (p < 0.05), with the same relationship being found between endometrium thickness at oocyte retrieval and miR-885-5p and miR-34a-5p (p < 0.05). In contrast, miR-1260a was found to be inversely associated with anti-Mullerian hormone (AMH; p = 0.007), while miR-365a-3p, miR122-5p, and miR-34a-5p correlated with embryo fertilization rates (p < 0.05). However, when omitting cases of male infertility (n = 15), miR122-5p remained significant (p < 0.05), while miR-365a-3p and miR-34a-5p no longer differed; interestingly, however, miR1260a and mir93.3p became significant (p = 0.0087/0.02, respectively). Furthermore, age was negatively associated with miR-335-3p, miR-28-5p, miR-155-5p, miR-501-3p, and miR-497-5p (p < 0.05). Live birth rate was negatively associated with miR-335-3p, miR-100-5p, miR-497-5p, let-7d, and miR-574-3p (p < 0.05), but these were not significant when age was accounted for.However, with the exclusion of male factor infertility, all those miRNAs were no longer significant, though miR.150.5p emerged as significant (p = 0.042). A beta-regression model identified miR-1260a, miR-486-5p, and miR-132-3p (p < 0.03, p = 0.0003, p < 0.00001, respectively) as the most predictive for fertilization rate. Notably, changes in detectable miRNAs were not linked to cleavage rate, top quality embryos (G3D3), and blastocyst or antral follicle count. An ingenuity pathway analysis showed that miRNAs associated with age were also associated with the variables found in reproductive system diseases.Conclusion: Plasma miRNAs prior to the IVF cycle were associated with differing demographic and IVF parameters, including age, and may be predictive biomarkers of fertilization rate.

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“…Insulin regulates hepatic GNG by transcriptional modulation and activation of the relative signaling pathways (Hatting et al, 2018). Even an indirect effect of insulin on extra hepatic tissues can be sufficient to maintain normal glucose metabolism (O-Sullivan et al, 2015). T2DM is characterized by excess glucagon and IR.…”

Section: Discussionmentioning

confidence: 99%

Combined Use of Astragalus Polysaccharide and Berberine Attenuates Insulin Resistance in IR-HepG2 Cells via Regulation of the Gluconeogenesis Signaling Pathway

et al. 2019

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Insulin resistance (IR) is likely to induce metabolic syndrome and type 2 diabetes mellitus (T2DM). Gluconeogenesis (GNG) is a complex metabolic process that may result in glucose generation from certain non-carbohydrate substrates. Chinese herbal medicine astragalus polysaccharides and berberine have been documented to ameliorate IR, and combined use of astragalus polysaccharide (AP) and berberine (BBR) are reported to synergistically produce an even better effect. However, what change may occur in the GNG signaling pathway of IR-HepG2 cells in this synergistic effect and whether AP-BBR attenuates IR by regulating the GNG signaling pathway remain unclear. For the first time, we discovered in this study that the optimal time of IR-HepG2 cell model formation was 48 h after insulin intervention. AP-BBR attenuated IR in HepG2 cells and the optimal concentration was 10 mg. AP-BBR reduced the intracellular H 2 O 2 content with no significant effect on apoptosis of IR-HepG2 cells. In addition, a rapid change was observed in intracellular calcium current of the IR-HepG2 cell model, and AP-BBR intervention attenuated this change markedly. The gene sequencing results showed that the GNG signaling pathway was one of the signaling pathways of AP-BBR to attenuate IR in IR-Hepg2 cells. The expression of p-FoxO1 Ser256 and PEPCK protein was increased, and the expression of GLUT2 protein was decreased significantly in the IR-HepG2 cell model, and both of these effects could be reversed by AP-BBR intervention. AP-BBR attenuated IR in IR-HepG2 cells, probably by regulating the GNG signaling Pathway.

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Erratum: FoxO1 integrates direct and indirect effects of insulin on hepatic glucose production and glucose utilization

Cited by 7 publications

References 0 publications

Antidiabetic Effect of Artemether in Db/Db Mice Involves Regulation of AMPK and PI3K/Akt Pathways

Antidiabetic Effect of Artemether in Db/Db Mice Involves Regulation of AMPK and PI3K/Akt Pathways

Association of microRNAs With Embryo Development and Fertilization in Women Undergoing Subfertility Treatments: A Pilot Study

Combined Use of Astragalus Polysaccharide and Berberine Attenuates Insulin Resistance in IR-HepG2 Cells via Regulation of the Gluconeogenesis Signaling Pathway

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