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Insulin sensitivity and aging

Insulin sensitivity and aging

RESEARCH BMI for Nutrition AND METHODS. Oral glucose tolerance test Insulin sensitivity and aging combined with senditivity nonlinear mixed-effect modeling population approach may be a useful technique to evaluate SI and secretion in a population. PTP1B phosphorylates IRS-1 tyrosine residues, thereby impairing insulin signaling [ ] and inducing skeletal muscle insulin resistance.

Insulin sensitivity and aging -

Tail vein blood was drawn to measure plasma insulin with a mouse insulin ELISA kit Novus and plasma glucose using a One Touch Ultra glucometer LifeScan. For the insulin-tolerance tests, mice were intraperitoneally administrated with 0.

Blood was drawn from tail veins for the measurement of blood glucose. Briefly, mice were catheterized with dual catheters MRE, Braintree Scientific for 4—5 days before the experiment.

Glucose uptake was quantified by measuring the radioactivity via scintillation. The level of circulating insulin receptors in mice was measured by ELISA as previously described with slight modification 5.

Briefly, the ELISA plate Perkin Elmer was coated with the monoclonal antibody against the α-subunit of the insulin receptor Invitrogen, AHR The signal amplification and detection were performed as described by the manufacturer of the ELISA plate.

AAV-WT MT1-MMP and AAV-MT1 EA virus produced by the pAAV-TBG-sfGFP-WPRE vector plasmid were purchased from Obio Technology Ltd. This vector plasmid was an AAV vector of serotype 8 under the control of the thyroxine-binding globulin TGB promoter, a well-documented AAV vector for specific transgene expression in hepatocytes.

They were delivered by tail vein injection 5. Mice were studied 4 weeks after AAV infection. The antibodies used in this study include the following: anti-MT1-MMP antibody ab, Abcam; for western blotting ; anti-insulin Rα antibody sc, Santa Cruz, for western blotting ; anti-insulin Rβ antibody sc, Santa Cruz, for western blotting ; anti-insulin Rβ antibody clone CT-3, MAB S65, millipore, for western blotting ; anti-Akt , Cell Signaling, for western blotting : anti-pAkt , Cell Signaling, for western blotting ; anti-β-actin , Cell Signaling, for western blotting ; goat anti-rabbit antibody conjugated with HRP sc, Santa Cruz, ; Rabbit anti-mouse antibody conjugated with HRP sc, Santa Cruz, Takeharu Sakamoto.

HEKT cells obtained from Prof. The cells have recently been tested negative for contamination of mycoplasma. The perfused liver was minced gently in DMEM.

Survived cells were used for the studies. The positive immunoreactions were detected with x-ray film Fuji by chemiluminescence using an ECL kit GE Healthcare. The relative expression of proteins was quantified using Image J software Wayne Rasband, NIH, USA. Protein bands of western blots were quantified using Image J version 1.

cDNA templates were then amplified with specific primers for target genes in the ABI ViiA 7 real-time PCR system Applied Biosystems using 2× SYBR Green PCR Master Mix Applied Biosystems.

Expression of the gene of interest of each sample was normalized to the endogenous control GAPDH, and presented as 2-ΔΔCt using the comparative Ct method. The results were analyzed by ViiA 7 Real-time PCR system software QuantStudio Software v1. The experiments were performed as previously described The recombinant catalytic domain of MT1-MMP BML-SE and recombinant Insulin Receptor H08H were purchased from Enzo and Sino Biological, respectively.

The rIR consists of human IR protein 1— amino acids. The protein mixture was subjected to western blotting analyses. Each experiment was independently performed for at least three times. Animal experiments involved at least three independent and randomly chosen mice at comparable developmental stages and none of the samples were excluded from analyses.

The sample size was determined from the power of the statistical test performed and was increased in accordance with the statistical variation.

All data meet the normal distribution. GraphPad Prism V8 for Window OS was used for statistical analyses. Further information on research design is available in the Nature Research Reporting Summary linked to this article. All data generated or analyzed during this study are included in this published article and its supplementary information files.

Source data are provided with this paper. Caro, J. et al. Insulin receptor kinase in human skeletal muscle from obese subjects with and without noninsulin dependent diabetes. Article CAS Google Scholar. Frojdo, S. Alterations of insulin signaling in type 2 diabetes: a review of the current evidence from humans.

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MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 99 , 81—92 Zhou, Z. Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I.

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Download references. The presented work was kindly supported by General Research Fund and , Health and Medical Research Fund and , National Natural Science Fund , and Guangdong Natural Science Foundation A and A School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. School of Biomedical Sciences, The University of Hong Kong, Hong Kong SAR, China.

Centre for Systems Biology Dresden, Max Planck Institute for Molecular Cell and Biology, Dresden, Germany. Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.

Respiratory Department, Jinhua Guangfu hospital, Jinhua, China. Centre for Chinese Herbal Medicine Drug Development Limited, Hong Kong Baptist University, Hong Kong SAR, China.

You can also search for this author in PubMed Google Scholar. This study was conceptualized by H. and X. Most of the experiments were performed by H. Some of the data were collected by H. provided experimental advices. Funding supporting this project was acquired by W.

and Z. This project was supervised by W. The manuscript was written by H. Correspondence to Zhao-Xiang Bian or Hoi Leong Xavier Wong. Nature Communications thanks Da-wei Zhang and the other, anonymous, reviewer s for their contribution to the peer review of this work.

Open Access This article is licensed under a Creative Commons Attribution 4. Reprints and permissions. Guo, X. Regulation of age-associated insulin resistance by MT1-MMP-mediated cleavage of insulin receptor.

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Skip to main content Thank you for visiting nature. nature nature communications articles article. Download PDF. Subjects Insulin signalling Type 2 diabetes. Abstract Insulin sensitivity progressively declines with age.

Introduction Aging in human is associated with the development of age-associated pathologies, including insulin resistance and hyperglycemia. Results Loss of MT1-MMP prevents aging- and obese-associated insulin resistance To understand the regulatory role of MT1-MMP in insulin sensitivity, we assessed the metabolic homeostasis of mice deficient in MT1-MMP.

Full size image. Discussion The mechanism underlying insulin resistance in physiological aging is not completely elucidated. Human plasma collection Young and elderly blood were collected for the isolation of EDTA plasma.

Metabolic measurement The metabolic measurement of mice was performed as previously described Adeno-associated virus AAV treatment AAV-WT MT1-MMP and AAV-MT1 EA virus produced by the pAAV-TBG-sfGFP-WPRE vector plasmid were purchased from Obio Technology Ltd.

Antibodies The antibodies used in this study include the following: anti-MT1-MMP antibody ab, Abcam; for western blotting ; anti-insulin Rα antibody sc, Santa Cruz, for western blotting ; anti-insulin Rβ antibody sc, Santa Cruz, for western blotting ; anti-insulin Rβ antibody clone CT-3, MAB S65, millipore, for western blotting ; anti-Akt , Cell Signaling, for western blotting : anti-pAkt , Cell Signaling, for western blotting ; anti-β-actin , Cell Signaling, for western blotting ; goat anti-rabbit antibody conjugated with HRP sc, Santa Cruz, ; Rabbit anti-mouse antibody conjugated with HRP sc, Santa Cruz, Cell treatment HEKT cells obtained from Prof.

In vitro MT1-MMP cleavage assay The experiments were performed as previously described Statistical analyses Each experiment was independently performed for at least three times.

Reporting summary Further information on research design is available in the Nature Research Reporting Summary linked to this article.

Data availability All data generated or analyzed during this study are included in this published article and its supplementary information files. References Caro, J.

Article CAS Google Scholar Frojdo, S. Article Google Scholar Olefsky, J. CAS PubMed Google Scholar Samuel, V. Article CAS Google Scholar Meakin, P. Article ADS Google Scholar Maesako, M. Article CAS Google Scholar Yuasa, T. Article CAS Google Scholar Soluble Insulin Receptor Study, G.

Article Google Scholar Holmbeck, K. Article CAS Google Scholar Zhou, Z. Article ADS CAS Google Scholar Gutierrez-Fernandez, A. Insulin resistance, a reduction in the rate of glucose disposal elicited by a given insulin concentration, is present in individuals who are obese, and those with diabetes mellitus, and may develop with aging.

Methods which are utilised to measure insulin sensitivity include the hyperinsulinaemic-euglycaemic and hyperglycaemic clamps and the intravenous glucose tolerance tests.

Several hormones and regulatory factors affect insulin action and may contribute to the insulin resistance observed in obesity.

In addition, abnormal free fatty acid metabolism plays an important role in insulin resistance and the abnormal carbohydrate metabolism seen in individuals who are obese or diabetic. Thus, the mechanisms underlying the development of insulin resistance are multifactorial, and also involve alterations of the insulin signalling pathway.

Aging is associated with an increase in bodyweight and fat mass. Not only is abdominal fat associated with hyperinsulinaemia but visceral adiposity is correlated with insulin resistance as well. Modifications of the changes in body composition with aging by diet and exercise training could delay the onset of insulin resistance.

Weight loss and aerobic and resistive exercise training result in losses of total body fat and abdominal fat. Several studies report that bodyweight loss increases insulin sensitivity and improves glucose tolerance.

In addition, the insulin resistance observed in aged persons can be modified by physical training.

Aging is characterized by Cutting-edge Fat Burner progressive wnd of physiological Inxulin leading to increase in the Insulin sensitivity and aging to death. This deterioration process Dextrose Pre-Workout in all living organisms and is sensitlvity primary risk factor for pathological conditions including obesity, type 2 diabetes mellitus, Alzheimer's disease and cardiovascular diseases. Most of the age-related diseases have been associated with impairment of action of an important hormone, namely insulin. It is well-known that this hormone is a critical mediator of metabolism, growth, proliferation and differentiation. Insulin action depends on two processes that determine its circulating levels, insulin secretion and clearance, and insulin sensitivity in its target tissues. Insulin sensitivity and aging

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