Podcasts about grk2

Curious about the science behind muscle health during menopause? In today's episode, I dove deep into the complexities of muscle protein synthesis, amino acid metabolism, and the impact of estrogen on women's well-being. Get ready to uncover the secrets of muscle loss, discover how estrogen plays a pivotal role in muscle building, and understand the intricate connection between amino acids, weight gain, and glucose production.   I break down various research, providing practical insights into personalized nutrition and exercise strategies tailored to your unique body composition and metabolic needs. Whether you're navigating weight concerns or aiming for optimal glucose levels, this episode is your go-to guide for evidence-based solutions. Tune in to gain a profound understanding of the importance of early intervention and the potential benefits of hormone replacement therapy.   This episode is packed with scientific insights, and I made sure to make it accessible and actionable for you. Remember, menopause is a powerful time in our lives, and with the right knowledge and tools, we can master it for better health and vitality. Key Takeaways: [00:02:14] Dietary intake and literature review. [00:03:16] Muscle protein synthesis. [00:07:34] Estrogen's role in muscle mass and function. [00:08:09] Estrogen regulation in skeletal muscle aging. [00:13:30] Estrogen and skeletal muscle regeneration. [00:15:45] Follicular stimulating hormone and muscle building. [00:18:20] Amino acid metabolism in overweight vs. lean individuals. [00:20:31] Gluconeogenesis in perimenopause and menopause. [00:24:06] Amino acid contribution to gluconeogenesis. [00:36:26] Metabolic signature and amino acid metabolism. [00:41:05] Personalized approaches to muscle health. [00:43:34] Metabolic changes and weight gain in menopause. [00:45:48] Hormone reset and metabolic flexibility. [00:50:21] Gender inequality in research and hormone replacement. Memorable Quotes:   "One weight training session, even if you whip your own butt with your trainer, is not enough because we don't have that same hardcore stimulus to muscle building that men have. So, a single session a week is not weight training. It is weight training for that one session, but it is not hard enough to cause significant muscle protein synthesis, particularly as we go through menopause." – Betty Murray   "If you're doing all the right things and you're not getting the right answers, it may be the order in which you're doing things. And it may be that you have to shift a little bit and go into a therapeutic diet for a period of time to force the body to become more metabolically efficient and become metabolically flexible." – Betty Murray     Links Mentioned: Free E-Book: A Woman's Guide to Kick-Ass Sleep FREE Quiz: Your Hormone Imbalance Type     Resources and References: Insulin resistance and the metabolism of branched-chain amino acids in humans Physical performance in relation to menopause status and physical activity The Emergence of the Metabolic Syndrome with Menopause The Greater Contribution of Gluconeogenesis to Glucose Production in Obesity Is Related to Increased Whole-Body Protein Catabolism The Role of Oestrogen in Female Skeletal Muscle Ageing: A Systematic Review The Role of Estrogen in Insulin Resistance Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health Separate Contribution of Diabetes, Total Fat Mass, and Fat Topography to Glucose Production, Gluconeogenesis, and Glycogenolysis Why does obesity cause diabetes? Protein Requirements of Pre-Menopausal Female Athletes: Systematic Literature Review A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance Follicle-stimulating hormone enhances hepatic gluconeogenesis by GRK2-mediated AMPK hyperphosphorylation at Ser485 in mice Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males Tracking the carbons supplying gluconeogenesis Weight gain during the menopause transition: Evidence for a mechanism dependent on protein leverage Role of branched-chain amino acid metabolism in the pathogenesis of obesity and type 2 diabetes-related metabolic disturbances BCAA metabolism in type 2 diabetes Branched-Chain and Aromatic Amino Acids Are Predictors of Insulin Resistance in Young Adults Estrogen Improves Insulin Sensitivity and Suppresses Gluconeogenesis via the Transcription Factor Foxo1 Connect with Betty Murray: Living Well Dallas Website Hormone Reset Website Betty Murray Website Facebook Instagram

Curious about the science behind muscle health during menopause? In today's episode, I dove deep into the complexities of muscle protein synthesis, amino acid metabolism, and the impact of estrogen on women's well-being. Get ready to uncover the secrets of muscle loss, discover how estrogen plays a pivotal role in muscle building, and understand the intricate connection between amino acids, weight gain, and glucose production.   I break down various research, providing practical insights into personalized nutrition and exercise strategies tailored to your unique body composition and metabolic needs. Whether you're navigating weight concerns or aiming for optimal glucose levels, this episode is your go-to guide for evidence-based solutions. Tune in to gain a profound understanding of the importance of early intervention and the potential benefits of hormone replacement therapy.   This episode is packed with scientific insights, and I made sure to make it accessible and actionable for you. Remember, menopause is a powerful time in our lives, and with the right knowledge and tools, we can master it for better health and vitality. Key Takeaways: [00:02:14] Dietary intake and literature review. [00:03:16] Muscle protein synthesis. [00:07:34] Estrogen's role in muscle mass and function. [00:08:09] Estrogen regulation in skeletal muscle aging. [00:13:30] Estrogen and skeletal muscle regeneration. [00:15:45] Follicular stimulating hormone and muscle building. [00:18:20] Amino acid metabolism in overweight vs. lean individuals. [00:20:31] Gluconeogenesis in perimenopause and menopause. [00:24:06] Amino acid contribution to gluconeogenesis. [00:36:26] Metabolic signature and amino acid metabolism. [00:41:05] Personalized approaches to muscle health. [00:43:34] Metabolic changes and weight gain in menopause. [00:45:48] Hormone reset and metabolic flexibility. [00:50:21] Gender inequality in research and hormone replacement. Memorable Quotes:   "One weight training session, even if you whip your own butt with your trainer, is not enough because we don't have that same hardcore stimulus to muscle building that men have. So, a single session a week is not weight training. It is weight training for that one session, but it is not hard enough to cause significant muscle protein synthesis, particularly as we go through menopause." – Betty Murray   "If you're doing all the right things and you're not getting the right answers, it may be the order in which you're doing things. And it may be that you have to shift a little bit and go into a therapeutic diet for a period of time to force the body to become more metabolically efficient and become metabolically flexible." – Betty Murray     Links Mentioned: Free E-Book: A Woman's Guide to Kick-Ass Sleep FREE Quiz: Your Hormone Imbalance Type     Resources and References: Insulin resistance and the metabolism of branched-chain amino acids in humans Physical performance in relation to menopause status and physical activity The Emergence of the Metabolic Syndrome with Menopause The Greater Contribution of Gluconeogenesis to Glucose Production in Obesity Is Related to Increased Whole-Body Protein Catabolism The Role of Oestrogen in Female Skeletal Muscle Ageing: A Systematic Review The Role of Estrogen in Insulin Resistance Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health Separate Contribution of Diabetes, Total Fat Mass, and Fat Topography to Glucose Production, Gluconeogenesis, and Glycogenolysis Why does obesity cause diabetes? Protein Requirements of Pre-Menopausal Female Athletes: Systematic Literature Review A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance Follicle-stimulating hormone enhances hepatic gluconeogenesis by GRK2-mediated AMPK hyperphosphorylation at Ser485 in mice Hepatic estrogen receptor α is critical for regulation of gluconeogenesis and lipid metabolism in males Tracking the carbons supplying gluconeogenesis Weight gain during the menopause transition: Evidence for a mechanism dependent on protein leverage Role of branched-chain amino acid metabolism in the pathogenesis of obesity and type 2 diabetes-related metabolic disturbances BCAA metabolism in type 2 diabetes Branched-Chain and Aromatic Amino Acids Are Predictors of Insulin Resistance in Young Adults Estrogen Improves Insulin Sensitivity and Suppresses Gluconeogenesis via the Transcription Factor Foxo1 Connect with Betty Murray: Living Well Dallas Website Hormone Reset Website Betty Murray Website Facebook Instagram

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.12.520050v1?rss=1 Authors: Radoux-Mergault, A., Oberhauser, L., Aureli, S., Gervasio, F. L., Stoeber, M. Abstract: G protein-coupled receptors in intracellular organelles can be activated in response to membrane permeant ligands, which contributes to the diversity and specificity of agonist action. The opioid receptors (ORs) provide a striking example, where opioid drugs activate ORs in the Golgi apparatus within seconds of drug addition. Till date, our knowledge on the signaling of intracellular GPCRs remains incomplete and it is unknown if the downstream effects triggered by ORs in plasma membrane and Golgi apparatus differ. To address this gap, we first assess the recruitment of signal transducers to ORs in both compartments. We find that Golgi-localized ORs couple to Gai/o probes and are phosphorylated by GPCR kinases (GRK2/3), but unlike plasma membrane receptors, do not recruit b-arrestin or a specific Ga probe. Subsequent molecular dynamics simulations with OR-transducer complexes in model bilayers mimicking plasma membrane or Golgi composition reveal that the lipid environment promotes location selective coupling. Unbiased global analyses then show that OR activation in the plasma membrane and Golgi apparatus has strikingly different downstream effects on transcription and protein phosphorylation. Taken together, the study delineates OR signal transduction with unprecedented spatial resolution and reveals that the subcellular location defines the signaling effect of opioid drugs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.19.512855v1?rss=1 Authors: Duan, J., Liu, H., Ji, Y., Yuan, Q., Li, X., Wu, K., Gao, T., Zhu, S., Jiang, Y., Yin, W., Xu, H. E. Abstract: Phosphorylation of G protein-coupled receptors (GPCR) by GPCR kinases (GRKs) desensitizes G protein signaling and promotes arrestin signaling, which is also modulated by biased ligands. Molecular assembly of GRKs to GPCRs and the basis of GRK-mediated biased signaling remain largely unknown due to the weak GPCR-GRK interactions. Here we report the complex structure of neurotensin receptor 1 (NTSR1) bound to GRK2, Gaq, and an arrestin-biased ligand, SBI-553, at a resolution of 2.92 Angstrom. The high-quality density map reveals the clear arrangement of the intact GRK2 with the receptor, with the N-terminal helix of GRK2 docking into the open cytoplasmic pocket formed by the outward movement of the receptor TM6, analogous of the binding of G protein to the receptor. Strikingly, the arrestin-biased ligand is found at the interface between GRK2 and NTSR1 to enhance GRK2 binding. The binding mode of the biased ligand is compatible with arrestin binding but is clashed with the binding of a G protein, thus provide an unambiguous mechanism for its arrestin-biased signaling capability. Together, our structure provides a solid model for understanding the details of GPCR-GRK interactions and biased signaling. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

References Dr Guerra's membrane immune synapse lectures Al-Aghbar, M.A., Jainarayanan, A.K., Dustin, M.L. et al. The interplay between membrane topology and mechanical forces in regulating T cell receptor activity. CommunBiol 5, 40 (2022). https://doi.org/10.1038/s42003-021-02995-1 Dinkel BA, Kremer KN, Rollins MR, Medlyn MJ, Hedin KE. GRK2 mediates TCR-induced transactivation of CXCR4 and TCR-CXCR4 complex formation that drives PI3Kγ/PREX1 signaling and T cell cytokine secretion. J Biol Chem. 2018 Sep 7;293(36):14022-14039. doi: 10.1074/jbc.RA118.003097. Epub 2018 Jul 17. PMID: 30018141; --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.17.302448v1?rss=1 Authors: Sahu, A., Sun, Y., Mukherjee, S., Witherow, C., Stenson, K., Tesmer, J. J. G., Mohan, M., Naga Prasad, S. N. Abstract: Insulin impairs {beta}2-adrenergic receptor ({beta}2AR) function through G protein-coupled receptor kinase 2 (GRK2) by phosphorylation but less is known about dephosphorylation mechanisms mediated by protein phosphatase 2A (PP2A). Pharmacologic or genetic inhibition of phosphoinositide 3-kinase {gamma} (PI3K{gamma}) unexpectedly resulted in significant reduction of insulin-mediated {beta}2AR phosphorylation. Interestingly, {beta}2AR-associated phosphatase activity was inhibited by insulin but was reversed by knock-down of PI3K{gamma} showing negative regulation of PP2A by PI3K{gamma}. Co-immunoprecipitation and surface plasmon resonance studies using purified proteins showed that GRK2 and PI3K{gamma} form a complex and could be recruited to {beta}2ARs as GRK2 interacts with insulin receptor substrate following insulin treatment. Consistently, {beta}-blocker pretreatment did not reduce insulin-mediated {beta}2AR phosphorylation indicating agonist- and G{beta}{gamma}-independent non-canonical regulation of receptor function. Mechanistically, PI3K{gamma} inhibits PP2A activity at the {beta}AR complex by phosphorylating an intracellular inhibitor of PP2A (I2PP2A). Knock-down or CRISPR ablation of endogenous I2PP2A unlocked PP2A inhibition mediating {beta}2AR dephosphorylation showing an unappreciated acute regulation of PP2A in mediating insulin-{beta}2AR cross-talk. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.17.301903v1?rss=1 Authors: Sun, Y., Gupta, M. K., Stenson, K., Mohan, M. L., Wanner, N., Asosinght, K., Erzurum, S., Naga Prasad, S. N. Abstract: Ischemia/hypoxia is major underlying cause for heart failure and stroke. Although beta-adrenergic receptor ({beta}AR) is phosphorylated in response to hypoxia, less is known about the underlying mechanisms. Hypoxia results in robust GRK2-mediated {beta}2AR phosphorylation but does not cause receptor internalization. However, hypoxia leads to significant endosomal-{beta}2AR phosphorylation accompanied by inhibition of {beta}2AR-associated protein phosphatase 2A (PP2A) activity impairing resensitization. Phosphoinositide 3-kinase {gamma} (PI3K{gamma}) impedes resensitization by phosphorylating endogenous inhibitor of protein phosphatase 2A, I2PP2A that inhibits PP2A activity. Hypoxia increased PI3K{gamma} activity leading to significant phosphorylation of I2PP2A resulting in inhibition of PP2A and consequently resensitization. Surprisingly, {beta}-blocker abrogated hypoxia-mediated {beta}2AR phosphorylation instead of phosphorylation in normoxia. Subjecting mice to hypoxia leads to significant cardiac dysfunction and {beta}2AR phosphorylation showing conservation of non-canonical hypoxia-mediated pathway in vivo. These findings provide mechanistic insights on hypoxia-mediated {beta}AR dysfunction which is rescued by {beta}-blocker and will have significant implications in heart failure and stroke. Copy rights belong to original authors. Visit the link for more info

Commentary by Dr. Valentin Fuster

Sarah Schumacher and Walter Koch explain how a GRK2-derived peptide reduces pathological cardiac hypertrophy in mice.

Cristina Murga and Rocio Vila-Bedmar explain why removing the kinase GRK2 prevents some of the metabolic consequences of a high-fat diet.

Walter Koch explains how S-nitrosothiols protect heart cells from ischemia-induced cell death.

Sat, 21 Jul 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15011/ https://edoc.ub.uni-muenchen.de/15011/1/Danowski_Nina.pdf Danowski, Nina

Upon activation the human bradykinin B2 receptor (B2R) acts as guanine nucleotide exchange factor for the G proteins Gq/11 and Gi. Thereafter, it gets phosphorylated by G protein-coupled receptor kinases (GRKs) and recruits beta-arrestins, which block further G protein activation and promote B2R internalization via clathrin-coated pits. As for most G protein-coupled receptors of family A, an intracellular helix 8 after transmembrane domain 7 is also predicted for the B2R. We show here that disruption of helix 8 in the B2R by either C-terminal truncation or just by mutation of a central amino acid (Lys-315) to a helix-breaking proline resulted in strong reduction of surface expression. Interestingly, this malfunction could be overcome by the addition of the membrane-permeable B2R antagonist JSM10292, suggesting that helix 8 has a general role for conformational stabilization that can be accounted for by an appropriate antagonist. Intriguingly, an intact helix 8, but not the C terminus with its phosphorylation sites, was indispensable for receptor sequestration and for interaction of the B2R with GRK2/3 and beta-arrestin2 as shown by co-immunoprecipitation. Recruitment of beta-arrestin1, however, required the presence of the C terminus. Taken together, our results demonstrate that helix 8 of the B2R plays a crucial role not only in efficient trafficking to the plasma membrane or the activation of G proteins but also for the interaction of the B2R with GRK2/3 and beta-arrestins. Additional data obtained with chimera of B2R with other G protein-coupled receptors of family A suggest that helix 8 might have similar functions in other GPCRs as well.

Sat, 11 Feb 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15560/ https://edoc.ub.uni-muenchen.de/15560/1/Thormann_Michael.pdf Thormann, Michael