scholarly journals Abnormal Glucose Metabolism in Male Mice Offspring Conceived by in vitro Fertilization and Frozen-Thawed Embryo Transfer

2021 ◽  
Vol 9 ◽  
Author(s):  
Ningxin Qin ◽  
Zhiyang Zhou ◽  
Wenlong Zhao ◽  
Kexin Zou ◽  
Weihui Shi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Signaling Pathway ◽  
Embryo Transfer ◽  
Glycogen Synthesis ◽  
Chow Group ◽  
Male Offspring ◽  
Insulin Tolerance ◽  
Thawed Embryo Transfer

Frozen and thawed embryo transfer (FET) is currently widely applied in routine assisted reproductive technology (ART) procedure. It is of great necessity to assess the safety of FET and investigate the long-term effect including glucose metabolism on FET-conceived offspring. The mouse model is a highly efficient method to figure out the relationship between the process of FET and offspring health. In this study, we obtained mouse offspring of natural conception (NC), in vitro fertilization (IVF), and FET. Glucose and insulin tolerance test (GTT/ITT) were performed on both chow fed or high fat diet (HFD) fed offspring to examine the glucose metabolism status. We detected hepatic PI3K/AKT pathway by western blotting and transcriptome status by RNA-sequencing. Impaired glucose tolerance (IGT) and decreased insulin tolerance were occurred in FET conceived male offspring. After challenged with the HFD-fed, male offspring in FET group performed earlier and severer IGT than IVF group. Furthermore, higher HOMA-IR index and higher serum insulin level post glucose injected in FET-chow group suggested the insulin resistance status. The PI3K/AKT signaling pathway, the major pathway of insulin in the liver, were also disrupted in FET group. Transcriptomics of the liver reveals significantly downregulated in glucose metabolic process and insulin resistance in the FET-chow group. In our study, FET-conceived male mouse offspring presented glucose metabolism dysfunction mainly manifesting insulin resistance. The hepatic insulin signaling pathway were in concordance with reduced glycogen synthesis, increased glycolysis and enhanced gluconeogenesis status in FET-conceived male offspring.

scholarly journals MiR-499-5p Contributes to Hepatic Insulin Resistance by Suppressing PTEN

2015 ◽  
Vol 36 (6) ◽  
pp. 2357-2365 ◽  
Author(s):  
Lei Wang ◽  
Ning Zhang ◽  
Hua-ping Pan ◽  
Zun Wang ◽  
Zhen-yu Cao
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathway ◽  
Glycogen Synthesis ◽  
Tolerance Test ◽  
Hepatic Insulin Resistance ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Tail Vein Injection ◽  
Insulin Tolerance ◽  
Dual Luciferase Reporter Assay

Background: Type 2 diabetes afflicts 95% of diabetes patients. Recent data suggest that miRNAs play a key role in insulin production, secretion and function. This study aims to explore the specific role of miR-499-5p in hepatic insulin resistance. Methods: The miRNA expression levels in the livers of db/db mice were analyzed using miRNA chips and were verified by real-time PCR. miR-499-5p mimics and an inhibitor were transfected into NCTC1469 cells. Then, the PI3K/AKT signaling pathway and glycogen level were determined. The target genes of miR-499-5p were predicted by bioinformatics and then confirmed by dual luciferase reporter assay and Western blot. To establish an insulin resistance (IR) animal model, C57BL/6 mice were fed a high-fat diet (HFD). The level of miR-499-5p in the livers of HFD-fed mice was upregulated through tail vein injection of adenovirus vectors (ad) containing miR-499-5p mimics. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to determine glucose tolerance and insulin tolerance, respectively. Results: MicroRNA chips and qPCR showed that miR-499-5p was significantly decreased in the livers of db/db mice. Downregulation of miR-499-5p impaired the insulin signaling pathway and glycogen synthesis, whereas upregulation of miR-499-5p promoted the insulin signaling pathway and glycogen synthesis in NCTC1469 cells. The dual luciferase reporter assay and Western blot demonstrated that PTEN was the target gene of miR-499-5p. Compared with the control group, miR-499-5p was increased 2.1-fold in the livers of HFD-fed mice. By tail vein injection of adenovirus vector containing miR-499-5p mimics, GTT and ITT were improved in HFD-fed mice. Conclusion: Downregulation of the miR-499-5p level impaired the PI3K/AKT/GSK signaling pathway and glycogen synthesis by targeting PTEN.

scholarly journals Metformin protects against insulin resistance induced by high uric acid in cardiomyocytes via AMPK signaling pathways in vitro and in vivo

2021 ◽  
Author(s):  
Zhenyu Jiao ◽  
Yingqun Chen ◽  
Yang Xie ◽  
Yanbing Li ◽  
Zhi Li
Keyword(s):  
Insulin Resistance ◽  
Uric Acid ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Mouse Model ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Abnormal Glucose Metabolism ◽  
Insulin Tolerance

Abstract BackgroundHigh uric acid (HUA) is associated with insulin resistance and abnormal glucose metabolism in cardiomyocytes. Metformin is a recognized agonist of AMP-activated protein kinase (AMPK) and an antidiabetic drug widely used for type 2 diabetes. It can play a cardioprotective role in many pathways. We investigated whether metformin protects against HUA-induced insulin resistance and abnormal glucose metabolism in cardiomyocytes.MethodsWe exposed primary cardiomyocytes to HUA, and cellular glucose uptake was quantified by measuring the uptake of 2-NBDG, a fluorescent glucose analog, after insulin excitation.ResultsTreatment with metformin (10 µmol/L) protected against HUA-inhibited glucose uptake induced by insulin in primary cardiomyocytes, as shown by fluorescence microscopy and flow cytometry analysis. HUA directly inhibited the phosphorylation of Akt and the translocation of glucose transporter type 4 (GLUT4) induced by insulin, which was blocked by metformin. Metformin promoted phosphorylation of AMPK, renewed HUA-inhibited glucose uptake induced by insulin and protected against insulin resistance in cardiomyocytes. As a result of these effects, in a mouse model of acute hyperuricemia, metformin improved insulin tolerance and glucose tolerance, accompanied by increased AMPK phosphorylation, Akt phosphorylation and translocation of GLUT4 in myocardial tissues. As expected, AICAR, another AMPK activator, had equivalent effects to metformin, demonstrating the important role of AMPK activation in protecting against insulin resistance induced by HUA in cardiomyocytes. Metformin protects against insulin resistance induced by HUA in cardiomyocytes and improves insulin tolerance and glucose tolerance in an acute hyperuricemic mouse model, along with the activation of AMPK.ConclusionsConsequently, metformin may be an important potential new treatment strategy for hyperuricemia-related cardiovascular disease.

Selective in vitro reversal of the insulin resistance of glucose transport in denervated rat skeletal muscle

1989 ◽  
Vol 257 (3) ◽  
pp. E418-E425 ◽  
Author(s):  
M. O. Sowell ◽  
S. L. Dutton ◽  
M. G. Buse
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Glucose Transport ◽  
Glycogen Synthesis ◽  
Insulin Response ◽  
Medium Composition ◽  
Insulin Resistant ◽  
Denervated Muscles

Denervation (24 h) of skeletal muscle causes severe postreceptor insulin resistance of glucose transport and glycogen synthesis that is demonstrable in isolated muscles after short (30 min) preincubations. After longer preincubations (2-4 h), the insulin response of glucose transport increased to normal, whereas glycogen synthesis remained insulin resistant. Basal and insulin-stimulated amino acid transport were significantly lower in denervated muscles than in controls after short or long incubations, although the percentage stimulation of transport by insulin was not significantly different. The development of glucose transport insulin resistance after denervation was not attributable to increased sensitivity to glucocorticoids or adenosine. The selective in vitro reversal of glucose transport insulin resistance was not dependent on medium composition, did not require protein or prostaglandin synthesis, and could not be attributed to release of a positive regulator into the medium. The data suggest 1) the insulin receptor in muscle stimulates glucose transport by a signaling pathway that is not shared by other insulin-sensitive effector systems, and 2) denervation may affect insulin receptor signal transduction at more than one site.

scholarly journals PPAR signaling pathway in the first trimester placenta from in vitro fertilization and embryo transfer

2019 ◽  
Vol 118 ◽  
pp. 109251 ◽  
Author(s):  
Liang Zhao ◽  
Xiuli Zheng ◽  
Jingfang Liu ◽  
Rong Zheng ◽  
Rui Yang ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Signaling Pathway ◽  
Embryo Transfer ◽  
First Trimester ◽  
Vitro Fertilization ◽  
Ppar Signaling

scholarly journals Resveratrol metabolites ameliorate insulin resistance in HepG2 hepatocytes by modulating IRS-1/AMPK

RSC Advances ◽  
2018 ◽  
Vol 8 (63) ◽  
pp. 36034-36042 ◽  
Author(s):  
Wendi Teng ◽  
Wenjing Yin ◽  
Liang Zhao ◽  
Changwei Ma ◽  
Jiaqiang Huang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Hepg2 Cell ◽  
Glycogen Synthesis ◽  
Ros Generation ◽  
Ampk Signaling ◽  
Ameliorate Insulin Resistance

RSV metabolites R3G and R4G protected HepG2 cell from insulin resistance by improving glucose uptake and glycogen synthesis, along with inhibiting ROS generation and modulating the RS-1/AMPK signaling pathway.

Frequent and mild scrotal heat stress in mice epigenetically alters glucose metabolism in the male offspring

2020 ◽  
Vol 319 (2) ◽  
pp. E291-E304
Author(s):  
Xiaoyan Wan ◽  
Xiaomei He ◽  
Qian Liu ◽  
Xiaotong Wang ◽  
Xiaofang Ding ◽  
...  
Keyword(s):  
Heat Stress ◽  
Glucose Metabolism ◽  
Male Infertility ◽  
Health Problems ◽  
Male Offspring ◽  
Epigenetic Mechanism ◽  
Altered Expression ◽  
Offspring Health ◽  
Ivf Et

Several studies have reported that health problems occur in assisted reproductive technology (ART)-conceived offspring. Recently, investigations have demonstrated that paternal environmental conditions influence offspring health. However, it is unclear whether the factors that cause male infertility per se affect offspring health and contribute to health problems in ART-born children. Scrotal heat stress represents a common cause for oligoasthenozoospermia, and in these cases, in vitro fertilization-embryo transfer (IVF-ET) is typically recommended for those individuals trying to conceive. We exposed C57BL/6J male mice to frequent and mild scrotal heat stress (fmSHS) (39°C for 30 min once weekly for 5 consecutive wk). Sperm was subjected to IVF-ET with oocytes of untreated C57BL/6J females to produce offspring mice. Glucose intolerance and insulin resistance was observed in the male offspring mice derived from fmSHS-exposed fathers. Islets, after evaluation, remained unchanged. Genes involved in glucose metabolism, especially, those in insulin signaling pathways, showed dysregulation in the liver of the fmSHS-derived male offspring. Differentially methylated regions were found in the sperm of fmSHS-exposed mice by whole genome bisulfite sequencing. Interestingly, abnormal methylation of some genes with altered expression in offspring was observed in both the sperm of fmSHS fathers and the liver of their male offspring. Our results suggest that the factors that cause male infertility can affect male offspring health by an epigenetic mechanism.

Prolonged suppression of glucose metabolism causes insulin resistance in rat skeletal muscle

1997 ◽  
Vol 272 (2) ◽  
pp. E288-E296 ◽  
Author(s):  
J. K. Kim ◽  
J. H. Youn
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Skeletal Muscles ◽  
Glycogen Synthesis ◽  
Whole Body ◽  
Metabolic Fluxes ◽  
Phosphate Inhibition ◽  
Intracellular Glucose

To determine whether an impairment of intracellular glucose metabolism causes insulin resistance, we examined the effects of suppression of glycolysis or glycogen synthesis on whole body and skeletal muscle insulin-stimulated glucose uptake during 450-min hyperinsulinemic euglycemic clamps in conscious rats. After the initial 150 min to attain steady-state insulin action, animals received an additional infusion of saline, Intralipid and heparin (to suppress glycolysis), or amylin (to suppress glycogen synthesis) for up to 300 min. Insulin-stimulated whole body glucose fluxes were constant with saline infusion (n = 7). In contrast, Intralipid infusion (n = 7) suppressed glycolysis by approximately 32%, and amylin infusion (n = 7) suppressed glycogen synthesis by approximately 45% within 30 min after the start of the infusions (P < 0.05). The suppression of metabolic fluxes increased muscle glucose 6-phosphate levels (P < 0.05), but this did not immediately affect insulin-stimulated glucose uptake due to compensatory increases in other metabolic fluxes. Insulin-stimulated whole body glucose uptake started to decrease at approximately 60 min and was significantly decreased by approximately 30% at the end of clamps (P < 0.05). Similar patterns of changes in insulin-stimulated glucose fluxes were observed in individual skeletal muscles. Thus the suppression of intracellular glucose metabolism caused decreases in insulin-stimulated glucose uptake through a cellular adaptive mechanism in response to a prolonged elevation of glucose 6-phosphate rather than the classic mechanism involving glucose 6-phosphate inhibition of hexokinase.

Sign in / Sign up

Export Citation Format

Share Document