Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 9, 2023

Adipocyte-derived extracellular vesicles (AdEVs) are membranous nanoparticles that convey communication from adipose tissue to other organs. Here, delineate their role as messengers with glucoregulatory nature, we paired fluorescence AdEV-tracing and SILAC-labeling (phospho)proteomics, revealed AdEVs transfer functional insulinotropic protein cargo into pancreatic β-cells. Upon transfer, AdEV proteins were subjects for phosphorylation, augmented GPCR/cAMP/PKA signaling by increasing total abundances phosphosite dynamics, ultimately enhanced 1st-phase glucose-stimulated insulin secretion (GSIS) in murine islets. Notably, effects restricted isolated obese resistant, but not lean mice, which was consistent differential loads luminal morphologies. Likewise, vivo pre-treatment mice amplified glucose tolerance mice. This data suggests secreted can inform β-cells about resistance order amplify GSIS times of increased demand.

Language: Английский

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Wearable, Sensing-Controlled, Ultrasound-Based Microneedle Smart System for Diabetes Management

ACS Sensors, Journal Year: 2023, Volume and Issue: 8(4), P. 1710 - 1722

Published: March 29, 2023

An intelligent closed-loop system that senses glucose and automatically delivers insulin can provide enhanced glycemic control for diabetes management. Here, we report the first time on development of a wearable, sensing-controlled, ultrasound-based microneedle smart Polylactic acid (PLA) hollow microneedles were fabricated by soft lithography maintain excellent mechanical strength stability in biofluids, followed deposition sensing electrodes outer layer. ultrasonic pump was constructed integrating lead zirconate titanate piezoelectric (PZT) ring biocompatible stainless-steel sheet with hundreds tapered holes top inner layer microneedles. Both sensor powered controlled printed circuit board (PCB). When device detects interstitial levels above normal, algorithm triggers to deliver into fluid through channels PLA The ultrasound from cause vaporization subcutaneous tissue fluid, accelerate diffusion rate, improve efficiency treatment utilization. has successfully demonstrated effective diabetic rats. showed high sensitivity 0.212 μA/mM at 0–28 mM detection limit 14 μM, mean absolute relative difference (MARD) 9.96% an average error 1.6 mM. flow rate 120 μL/min, glucose-lowering 4 mM/h. This work may open new paradigm systems management, as well wide range practical applications patients.

Language: Английский

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Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: March 3, 2023

Abstract Diabetes mellitus is a heterogeneous chronic metabolic disorder characterized by the presence of hyperglycemia, commonly preceded prediabetic state. The excess blood glucose can damage multiple organs, including brain. In fact, cognitive decline and dementia are increasingly being recognized as important comorbidities diabetes. Despite largely consistent link between diabetes dementia, underlying causes neurodegeneration in diabetic patients remain to be elucidated. A common factor for almost all neurological disorders neuroinflammation, complex inflammatory process central nervous system most part orchestrated microglial cells, main representatives immune this context, our research question aimed understand how affects brain and/or retinal microglia physiology. We conducted systematic search PubMed Web Science identify items addressing effects on phenotypic modulation, critical neuroinflammatory mediators their pathways. literature yielded 1327 records, 18 patents. Based title abstracts, 830 papers were screened from which 250 primary met eligibility criteria (original articles with or strict model without comorbidities, that included direct data about retina), 17 additional through forward backward citations, resulting total 267 scoping review. reviewed publications investigating its pathophysiological traits microglia, vitro studies, preclinical models clinical studies patients. Although classification remains elusive given capacity adapt environment morphological, ultrastructural molecular dynamism, modulates states, triggering specific responses include upregulation activity markers (such Iba1, CD11b, CD68, MHC-II F4/80), morphological shift amoeboid shape, secretion wide variety cytokines chemokines, reprogramming generalized increase oxidative stress. Pathways activated diabetes-related conditions NF-κB, NLRP3 inflammasome, fractalkine/CX3CR1, MAPKs, AGEs/RAGE Akt/mTOR. Altogether, detailed portrait interactions physiology presented here regarded an starting point future focused microglia–metabolism interface.

Language: Английский

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Animal models for type 1 and type 2 diabetes: advantages and limitations

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 20, 2024

Diabetes mellitus, commonly referred to as diabetes, is a group of metabolic disorders characterized by chronic elevation in blood glucose levels, resulting from inadequate insulin production, defective cellular response extracellular insulin, and/or impaired metabolism. The two main types that account for most diabetics are type 1 diabetes mellitus (T1DM) and 2 (T2DM), each with their own pathophysiological features. T1D an autoimmune condition where the body’s immune system attacks destroys insulin-producing beta cells pancreas. This leads lack vital hormone regulating sugar levels uptake. As result, those depend on lifelong therapy control level. In contrast, T2DM resistance, do not respond effectively coupled relative deficiency. form often associated obesity, sedentary lifestyle, genetic factors, it managed lifestyle changes oral medications. Animal models play crucial role research. However, given distinct differences between T1DM T2DM, imperative researchers employ specific animal tailored better understanding mechanisms underlying condition, assessing efficacy new therapeutics. this review, we discuss used research strengths limitations.

Language: Английский

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ONOO–-activatable and LD-traced NIR fluorescent probe for mechanism study and early diagnosis of NAFLD and diabetes induced liver injury

Sensors and Actuators B Chemical, Journal Year: 2024, Volume and Issue: 412, P. 135806 - 135806

Published: April 10, 2024

Language: Английский

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