Trends in insulin resistance: insights into mechanisms and therapeutic strategy

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 6, 2022

The centenary of insulin discovery represents an important opportunity to transform diabetes from a fatal diagnosis into medically manageable chronic condition. Insulin is key peptide hormone and mediates the systemic glucose metabolism in different tissues. resistance (IR) disordered biological response for stimulation through disruption molecular pathways target Acquired conditions genetic factors have been implicated IR. Recent biochemical studies suggest that dysregulated metabolic mediators released by adipose tissue including adipokines, cytokines, chemokines, excess lipids toxic lipid metabolites promote IR other associated with several groups abnormal syndromes include obesity, diabetes, dysfunction-associated fatty liver disease (MAFLD), cardiovascular disease, polycystic ovary syndrome (PCOS), abnormalities. Although no medication specifically approved treat IR, we summarized lifestyle changes pharmacological medications used as efficient intervention improve sensitivity. Ultimately, systematic discussion complex mechanism will help identify potential new targets closely

Language: Английский

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Emerging Targets in Type 2 Diabetes and Diabetic Complications

Advanced Science, Journal Year: 2021, Volume and Issue: 8(18)

Published: July 28, 2021

Abstract Type 2 diabetes is a metabolic, chronic disorder characterized by insulin resistance and elevated blood glucose levels. Although large drug portfolio exists to keep the levels under control, these medications are not without side effects. More importantly, once diagnosed rarely reversible. Dysfunctions in kidney, retina, cardiovascular system, neurons, liver represent common complications of diabetes, which again lack effective therapies that can reverse organ injury. Overall, molecular mechanisms how type develops leads irreparable damage remain elusive. This review particularly focuses on novel targets may play role pathogenesis diabetes. Further research eventually pave way for treatment—or even prevention—of along with its complications.

Language: Английский

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Diabetic vascular diseases: molecular mechanisms and therapeutic strategies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: April 10, 2023

Abstract Vascular complications of diabetes pose a severe threat to human health. Prevention and treatment protocols based on single vascular complication are no longer suitable for the long-term management patients with diabetes. Diabetic panvascular disease (DPD) is clinical syndrome in which vessels various sizes, including macrovessels microvessels cardiac, cerebral, renal, ophthalmic, peripheral systems diabetes, develop atherosclerosis as common pathology. Pathological manifestations DPDs usually manifest macrovascular atherosclerosis, well microvascular endothelial function impairment, basement membrane thickening, microthrombosis. Cardiac, microangiopathy coexist microangiopathy, while renal retinal predominantly microangiopathic. The following associations exist between DPDs: numerous similar molecular mechanisms, risk-predictive relationships diseases. Aggressive glycemic control combined early comprehensive intervention key prevention treatment. In addition widely recommended metformin, glucagon-like peptide-1 agonist, sodium-glucose cotransporter-2 inhibitors, latest aldose reductase peroxisome proliferator-activated receptor-γ agonizts, glucokinases mitochondrial energy modulators, etc. under active development. proposed obtain more systematic care requires center focusing This would leverage advantages cross-disciplinary approach achieve better integration pathogenesis therapeutic evidence. Such strategy confer benefits promote development DPD discipline.

Language: Английский

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Specific Nanodrug for Diabetic Chronic Wounds Based on Antioxidase-Mimicking MOF-818 Nanozymes

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(51), P. 23438 - 23447

Published: Dec. 13, 2022

Chronic wound is a common complication for diabetic patients, which entails substantial inconvenience, persistent pain, and significant economic burden to patients. However, current clinical treatments chronic wounds remain unsatisfactory. A prolonged but ineffective inflammation phase in the primary difference between normal wounds. Herein, we present an effective antioxidative system (MOF/Gel) healing of rats through integrating metal organic framework (MOF) nanozyme with antioxidant enzyme-like activity hydrogel (Gel). MOF/Gel can continuously scavenge reactive oxygen species modulate oxidative stress microenvironment wounds, leads natural transition from proliferation phase. Impressively, efficacy one-time-applied was comparable that human epidermal growth factor Gel, widely used drug various treatments. Such effective, safe, convenient meet complex demands.

Language: Английский

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Diabetes mellitus: Classification, mediators, and complications; A gate to identify potential targets for the development of new effective treatments

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115734 - 115734

Published: Oct. 17, 2023

Nowadays, diabetes mellitus has emerged as a significant global public health concern with remarkable increase in its prevalence. This review article focuses on the definition of and classification into different types, including type 1 (idiopathic fulminant), 2 diabetes, gestational hybrid forms, slowly evolving immune-mediated ketosis-prone other special types. Diagnostic criteria for are also discussed. The role inflammation both is explored, along mediators potential anti-inflammatory treatments. Furthermore, involvement various organs highlighted, such adipose tissue obesity, gut microbiota, pancreatic β-cells. manifestation Langerhans β-cell islet inflammation, oxidative stress, impaired insulin production secretion addressed. Additionally, impact liver cirrhosis, acute kidney injury, immune system complications, diabetic complications like retinopathy neuropathy examined. Therefore, further research required to enhance diagnosis, prevent chronic identify therapeutic targets management associated dysfunctions.

Language: Английский

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Glycopeptide‐Based Multifunctional Hydrogels Promote Diabetic Wound Healing through pH Regulation of Microenvironment

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(29)

Published: April 23, 2023

Abstract Excessive inflammation, bacterial infection, and blocked angiogenesis make diabetic wound healing challenging. Multifunctional dressings have several advantages in healing. In addition, the pH regulation of microenvironment is shown to be a key factor that promotes skin regeneration through cellular immune regulation. However, few reports focused on development functional with ability regulate promote This study presents novel approach for regulating sites using glycopeptide‐based hydrogel consisting modified hyaluronic acid poly(6‐aminocaproic acid). forms network Schiff base interactions metal complexation, which suppresses inflammation accelerates during Hydrogels not only adequate mechanical properties self‐healing but can also support tissue adhesion. They secretion inducible cAMP early repressor, polarization macrophages toward M2 type. The vivo results confirm repair by exerting rapid anti‐inflammatory effects promoting angiogenesis. Therefore, this system represents an effective strategy treating wounds.

Language: Английский

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Glycosaminoglycan-Based Hydrogel Delivery System Regulates the Wound Microenvironment to Rescue Chronic Wound Healing

ACS Applied Materials & Interfaces, Journal Year: 2022, Volume and Issue: 14(28), P. 31737 - 31750

Published: July 8, 2022

Chronic wounds cannot proceed through the normal, orderly, and timely sequence of repair. The adverse cycle between excess reactive oxide species (ROS) a persistent inflammatory response is an important mechanism impaired wound healing. Herein, by combining intrinsic bioactivities natural polysaccharides drugs, glycosaminoglycan-based hydrogel delivery system proposed to regulate microenvironment. Dynamic supramolecular cross-linking enables easily encapsulate drug fully fill area. As backbone hydrogel, heparin captures chemokines at site, while hyaluronic acid mimics function ECM. hydrophobic curcumin has been ingeniously encapsulated in micellization, thereby exerting good ROS scavenging ability anti-inflammatory activity. Evaluations diabetic mice showed that this antioxidant was effective reducing influx immune cells site down-regulating response. Accelerated healing also observed, as evidenced faster re-epithelialization better ECM remodeling. can microenvironment from multiple aspects achieve regression repair, which may provide new therapeutic strategy for chronic wounds.

Language: Английский

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Association between the triglyceride glucose (TyG) index and the risk of acute kidney injury in critically ill patients with heart failure: analysis of the MIMIC-IV database

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: Aug. 31, 2023

Abstract Background Insulin resistance (IR) can be effectively assessed using the dependable surrogate biomarker triglyceride-glucose (TyG) index. In various critical care contexts, like contrast-induced acute kidney injury (AKI), an elevated TyG index has demonstrated a robust correlation with incidence of AKI. Nonetheless, potential to predict AKI in critically ill patients heart failure (HF) remains uncertain. Methods A cohort participants was non-consecutively selected from Medical Information Mart for Intensive Care IV (MIMIC-IV) database and divided into quartiles based on their values. The primary outcome. secondary endpoint in-hospital mortality within both whole study population subset patients. use renal replacement therapy (RRT) which represented progression severity also included as representing restricted cubic splines model Cox proportional hazards models were utilized evaluate association risk HF condition. Kaplan-Meier survival analysis employed estimate disparities across groups differentiated by Results This total 1,393 patients, 59% being male. 82.8%. analyses revealed significant between HF. illustrated linear relationship higher increased this specific patient population. Furthermore, unveiled statistically differences RRT Conclusions results highlight independent predictor poor outcome However, further confirmation causality necessitates larger prospective studies.

Language: Английский

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Enzyme-responsive microneedle patch for bacterial infection and accelerated healing of diabetic wounds

Chemical Engineering Journal, Journal Year: 2023, Volume and Issue: 466, P. 143126 - 143126

Published: April 30, 2023

Language: Английский

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Lymphatic vessel: origin, heterogeneity, biological functions, and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 3, 2024

Abstract Lymphatic vessels, comprising the secondary circulatory system in human body, play a multifaceted role maintaining homeostasis among various tissues and organs. They are tasked with serious of responsibilities, including regulation lymph absorption transport, orchestration immune surveillance responses. vessel development undergoes series sophisticated regulatory signaling pathways governing heterogeneous-origin cell populations stepwise to assemble into highly specialized lymphatic networks. Lymphangiogenesis, as defined by new vessels sprouting from preexisting vessels/embryonic veins, is main developmental mechanism underlying formation expansion networks an embryo. However, abnormal lymphangiogenesis could be observed many pathological conditions has close relationship progression diseases. Mechanistic studies have revealed set lymphangiogenic factors cascades that may serve potential targets for regulating lymphangiogenesis, further modulate Actually, increasing number clinical trials demonstrated promising interventions showed feasibility currently available treatments future translation. Targeting promoters or inhibitors not only directly regulates but improves efficacy diverse treatments. In conclusion, we present comprehensive overview physiological functions, describe critical involvement multiple Moreover, summarize targeting therapeutic values providing novel perspectives treatment strategy

Language: Английский

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