Personalized phosphoproteomics of skeletal muscle insulin resistance and exercise links MINDY1 to insulin action DOI Creative Commons
Elise J. Needham, Janne R. Hingst, Johan Onslev

и другие.

Cell Metabolism, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Type 2 diabetes is preceded by a defective insulin response, yet our knowledge of the precise mechanisms incomplete. Here, we investigate how resistance alters skeletal muscle signaling and exercise partially counteracts this effect. We measured parallel phenotypes phosphoproteomes insulin-resistant (IR) insulin-sensitive (IS) men as they responded to (n = 19, 114 biopsies), quantifying over 12,000 phosphopeptides in each biopsy. Insulin involves selective time-dependent alterations signaling, including reduced insulin-stimulated mTORC1 non-canonical responses. Prior promotes sensitivity even IR individuals "priming" portion prior infusion. This includes MINDY1 S441, which show an AKT substrate. found that knockdown enhances glucose uptake rat myotubes. work delineates identifies regulator action.

Язык: Английский

Editorial: Lipid metabolism dysregulation in obesity-related diseases and neurodegeneration DOI Creative Commons
Jialiu Zeng, Chih Hung Lo

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Фев. 11, 2025

Editorial: Lipid Metabolism Dysregulation in Obesity-Related Diseases and Neurodegeneration Provisionally accepted

Язык: Английский

Процитировано

2
Top-Down Proteomic Profiling of Protein Corona by High-Throughput Capillary Isoelectric Focusing-Mass Spectrometry DOI Creative Commons

Reyhane Tabatabaeian Nimavard,

Seyed Amirhossein Sadeghi,

Morteza Mahmoudi

и другие.

Journal of the American Society for Mass Spectrometry, Год журнала: 2025, Номер unknown

Опубликована: Март 2, 2025

In the rapidly evolving field of nanomedicine, understanding interactions between nanoparticles (NPs) and biological systems is crucial. A pivotal aspect these formation a protein corona when NPs are exposed to fluids (e.g., human plasma), which significantly influences their behavior functionality. This study introduces an advanced capillary isoelectric focusing tandem mass spectrometry (cIEF-MS/MS) platform designed enable high-throughput reproducible top-down proteomic analysis corona. Our cIEF-MS/MS technique completed each within 30 min. It produced proteoform measurements for at least 50 runs regarding proteoforms' migration time [relative standard deviations (RSDs) <4%], intensity (Pearson's correlation coefficients any two >0.90), number identifications (71 ± 10), proteoform-spectrum matches (PrSMs) (196 30). Of 53 identified genes, 33 potential biomarkers various diseases cancer, cardiovascular disease, Alzheimer's disease). We 1-102 proteoforms per biomarker, containing sequence variations or post-translational modifications. Delineating in by our fashion will benefit nanobiointeractions advance both diagnostic therapeutic nanomedicine technologies.

Язык: Английский

Процитировано

1
Proteome of Renal Tubuli and Serum Differentiate Pre‐Existing Type 2 Diabetes and Post‐Transplant Diabetes in Kidney Transplant Recipients DOI Creative Commons

Eleni Skandalou,

Mariell Rivedal, Hans‐Peter Marti

и другие.

PROTEOMICS - CLINICAL APPLICATIONS, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

Diabetes mellitus (DM) is a major cause of end-stage kidney disease (ESKD), with transplantation being the preferred treatment. However, post-transplant diabetes (PTDM) increases mortality and graft loss. While PTDM Type 2 (T2DM) share risk factors, their mechanisms differ, particularly in diabetic nephropathy (DN). This study aimed to investigate molecular differences by mapping proteomes proximal tubuli serum normoglycemic (NG), pre-transplant T2DM, patients one year post-transplantation. Experimental Design Proteomic analysis was performed on microdissected tubular cells samples from transplant recipients categorized as NG, or at Mass spectrometry used identify differentially expressed proteins. Data analyses were using gene ontology databases pathway analysis. revealed key differences, including significant dysregulation mitochondrial proteins lipid metabolism pathways compared T2DM NG groups. Additionally, we observed distinct patterns cholesterol PTDM, highlighting complex interplay between fatty acid metabolism, dysfunction systemic that may drive renal injury PTDM-related DN. pilot first perform proteomic both recipients. The could help develop targeted therapies early diagnostic markers, ultimately improving outcomes patient management. Further research needed validate these findings explore therapeutic potential.

Язык: Английский

Процитировано

0
Novel secreted regulators of glucose and lipid metabolism in the development of metabolic diseases DOI
Lianna W. Wat, Katrin J. Svensson

Diabetologia, Год журнала: 2024, Номер 67(12), С. 2626 - 2636

Опубликована: Авг. 24, 2024

Язык: Английский

Процитировано

2
Innovative Drug Discovery: Targeting Cancer, Neurological Disorders, and Obesity DOI Creative Commons
Robert B. Kargbo

ACS Medicinal Chemistry Letters, Год журнала: 2024, Номер 15(9), С. 1440 - 1442

Опубликована: Авг. 21, 2024

The landscape of therapeutic innovation is rapidly evolving, with significant advances in cancer treatment, obesity management, and the modulation protein interactions neurodegenerative disorders. This Patent Highlight explores scientific breakthroughs described four recent patents covering novel compounds, advanced methods for identifying E3 ligase substrates, developing new strategies combating its related metabolic These innovations, focusing on specific molecular targets pathways, promise more effective personalized treatment options, addressing unmet needs oncology, neurology, health.

Язык: Английский

Процитировано

0
Circulating Proteomic Profiles in Women with Morbid Obesity Compared to Normal-Weight Women DOI Creative Commons
Laia Bertran, Elena Cristina Rusu, María Guirro

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Авг. 30, 2024

Abstract In this study, we aimed to evaluate circulating proteomic levels in women with morbid obesity (MO) compared normal-weight (NW) women. Moreover, have the profile between metabolically healthy (MH) MO and those type 2 diabetes mellitus (T2DM). The study included 66 129 (54 MH 75 T2DM). Blood samples were processed for proteomics, involving protein extraction, quantification, digestion peptide labelling NanoLC-(Orbitrap)MS/MS analysis. Statistical analyses performed. We identified 257 proteins. Women showed significantly increased of 35 proteins decreased 45 NW Enrichment analysis metabolic pathways revealed significant findings. an altered women, related chylomicron assembly, complement cascade, clotting insulin growth factor system. Regarding T2DM MHMO shows alterations mostly same associated obesity. These findings confirmed previous reports can help us better understand pathophysiology diseases.

Язык: Английский

Процитировано

0
Personalized phosphoproteomics of skeletal muscle insulin resistance and exercise links MINDY1 to insulin action DOI Creative Commons
Elise J. Needham, Janne R. Hingst, Johan Onslev

и другие.

Cell Metabolism, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Type 2 diabetes is preceded by a defective insulin response, yet our knowledge of the precise mechanisms incomplete. Here, we investigate how resistance alters skeletal muscle signaling and exercise partially counteracts this effect. We measured parallel phenotypes phosphoproteomes insulin-resistant (IR) insulin-sensitive (IS) men as they responded to (n = 19, 114 biopsies), quantifying over 12,000 phosphopeptides in each biopsy. Insulin involves selective time-dependent alterations signaling, including reduced insulin-stimulated mTORC1 non-canonical responses. Prior promotes sensitivity even IR individuals "priming" portion prior infusion. This includes MINDY1 S441, which show an AKT substrate. found that knockdown enhances glucose uptake rat myotubes. work delineates identifies regulator action.

Язык: Английский

Процитировано

0