Type II diabetes mellitus: a review on recent drug based therapeutics

Biomedicine & Pharmacotherapy, Год журнала: 2020, Номер 131, С. 110708 - 110708

Опубликована: Сен. 10, 2020

Diabetes mellitus (DM) is a metabolic disorder that occurs in the body because of decreased insulin activity and/or secretion. Pathological changes such as nephropathy, retinopathy, and cardiovascular complications inevitably occur with progression disease. DM mainly categorized into 2 sub-types, type I II DM. While generally treated through replacement therapy, oral hypoglycaemics. The major drug therapy for comprises secretagogues, biguanides, sensitizers, alpha glucosidase inhibitors, incretin mimetics, amylin antagonists sodium-glucose co-transporter-2 (SGLT2) inhibitors. Dual therapies are often recommended patients who unable to achieve therapeutic goals first line hypoglycaemic agents monotherapy. Inspite appreciable benefits, conventional dosage forms depicts differential bioavailability short half-life, mandating frequent causing greater side effects leading ineffectiveness patient non-compliance. Given pathological complexity said disease, nanotechnology-based approaches more enticing it comes added advantage site-specific delivery higher reduced regimen. In present review article, we have made an attempt explore pathophysiology DM, treatment (mono combination therapy) well nano based

Язык: Английский

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Bioactive Compounds in Anti-Diabetic Plants: From Herbal Medicine to Modern Drug Discovery

Biology, Год журнала: 2020, Номер 9(9), С. 252 - 252

Опубликована: Авг. 28, 2020

Natural products, including organisms (plants, animals, or microorganisms) have been shown to possess health benefits for animals and humans. According the estimation of World Health Organization, in developing countries, 80% population has still depended on traditional medicines folk which are mostly prepared from plant prevention treatment diseases. Traditional medicine extracts proved be more affordable, clinically effective relatively less adverse effects than modern drugs. Literature shows that attention application phytochemical constituents medicinal plants pharmaceutical industry increased significantly. Plant-derived secondary metabolites small molecules macromolecules biosynthesized steroids, alkaloids, phenolic, lignans, carbohydrates glycosides, etc. a diversity biological properties beneficial humans, such as their antiallergic, anticancer, antimicrobial, anti-inflammatory, antidiabetic antioxidant activities Diabetes mellitus is chronic disease result metabolic disorders pancreas β-cells hyperglycemia. Hyperglycemia can caused by deficiency insulin production pancreatic (Type 1 diabetes mellitus) insufficiency face resistance 2 mellitus). The current medications focus controlling lowering blood glucose levels vessel normal level. However, most drugs many side causing some serious medical problems during period treating. Therefore, used long time play an important role alternative medicines. Moreover, past few years, new bioactive isolated showed activity with efficacy oral hypoglycemic agents clinical therapy. performed good practice showing bright future therapy mellitus. Organization pointed out this its complications not only major challenge future, but essential if all attained. paper briefly reviews active compounds, pharmacological popular widely diabetic treatment. Morphological data V-herb database each species was also included identification.

Язык: Английский

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ACSL4 deficiency confers protection against ferroptosis-mediated acute kidney injury

Redox Biology, Год журнала: 2022, Номер 51, С. 102262 - 102262

Опубликована: Фев. 9, 2022

The term ferroptosis coined in 2012 causes acute kidney injury (AKI). However, its pathway mechanism AKI is poorly understood. In this study, we conducted an RNA-sequence analysis of kidneys and normal mice to explore the ferroptosis. Consequently, differentially expressed genes highlighted Acyl-CoA synthetase long-chain family (ACSL4), a known promotor for Besides, RT-PCR, Western blot, immunohistochemical analyses confirmed upregulation. HIF-1α was downregulated I/R-AKI mice, vitro studies negative regulation on ACSL4. To role ACSL4 AKI, constructed knockout tubules mice-as Cdh16Cre-ACSL4F/F mice. Results revealed that significantly reduced inhibited functional pathological Meanwhile, demonstrated decreased inflammation macrophage infiltration. Further, additional explorations were explored decipher more thorough understanding ferroptotic immunogenicity. As result, neutrophils not directly recruited by cells, but cell-induced macrophages. inhibitor rosiglitazone AKI. Collectively, these data provide novel insights into pathogenesis, defined as effective target

Язык: Английский

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Lipid metabolism in sickness and in health: Emerging regulators of lipotoxicity

Molecular Cell, Год журнала: 2021, Номер 81(18), С. 3708 - 3730

Опубликована: Сен. 1, 2021

Язык: Английский

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Treatment of type 2 diabetes: challenges, hopes, and anticipated successes

The Lancet Diabetes & Endocrinology, Год журнала: 2021, Номер 9(8), С. 525 - 544

Опубликована: Июнь 25, 2021

Язык: Английский

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Trends in Antidiabetic Drug Discovery: FDA Approved Drugs, New Drugs in Clinical Trials and Global Sales

Frontiers in Pharmacology, Год журнала: 2022, Номер 12

Опубликована: Янв. 19, 2022

Type 2 diabetes mellitus (T2DM) continues to be a substantial medical problem due its increasing global prevalence and because chronic hyperglycemic states are closely linked with obesity, liver disease several cardiovascular diseases. Since the early discovery of insulin, numerous antihyperglycemic drug therapies treat have been approved, also discontinued, by United States Food Drug Administration (FDA). To provide an up-to-date account current trends antidiabetic pharmaceuticals, this review offers comprehensive analysis main classes compounds their mechanisms: insulin types, biguanides, sulfonylureas, meglitinides (glinides), alpha-glucosidase inhibitors (AGIs), thiazolidinediones (TZD), incretin-dependent therapies, sodium-glucose cotransporter type (SGLT2) combinations thereof. The number therapeutic alternatives T2DM now there nearly 60 drugs approved FDA. Beyond 100 additional agents being evaluated in clinical trials. In addition standard treatments therapy metformin, new combinations, e.g., containing SGLT2 dipeptidyl peptidase-4 (DPP4) inhibitors, that gained use during last decade. Furthermore, interesting alternatives, such as lobeglitazone, efpeglenatide tirzepatide, ongoing Modern drugs, glucagon-like peptide-1 (GLP-1) receptor agonists, DPP4 popularity on pharmaceutical market, while less expensive over counter developing economies. large heterogeneity is creating push towards more personalized accessible treatments. We describe trials, which may help achieve near future.

Язык: Английский

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Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: a systematic review

˜The œLancet. Gastroenterology & hepatology, Год журнала: 2022, Номер 7(4), С. 367 - 378

Опубликована: Янв. 12, 2022

Язык: Английский

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GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice

Journal of Clinical Investigation, Год журнала: 2021, Номер 131(12)

Опубликована: Май 18, 2021

Tirzepatide (LY3298176), a dual GIP and GLP-1 receptor (GLP-1R) agonist, delivered superior glycemic control weight loss compared with GLP-1R agonism in patients type 2 diabetes. However, the mechanism by which tirzepatide improves efficacy how (GIPR) contributes is not fully understood. Here, we show that an effective insulin sensitizer, improving sensitivity obese mice to greater extent than agonism. To determine whether GIPR contributes, effect of WT Glp-1r–null mice. In absence GLP-1R–induced loss, improved enhancing glucose disposal white adipose tissue (WAT). support this, long-acting agonist (LAGIPRA) was found enhance augmenting WAT. Interestingly, LAGIPRA on associated reduced branched-chain amino acids (BCAAs) ketoacids circulation. Insulin sensitization upregulation genes catabolism glucose, lipid, BCAAs brown tissue. Together, our studies weight-dependent -independent manner. These results highlight therapeutic profile dual-receptor agonism, offering mechanistic insights into clinical tirzepatide.

Язык: Английский

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COVID-19 and diabetes: The why, the what and the how

Journal of Diabetes and its Complications, Год журнала: 2020, Номер 34(9), С. 107637 - 107637

Опубликована: Май 22, 2020

Язык: Английский

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Insulin resistance and cardiovascular disease

Journal of International Medical Research, Год журнала: 2023, Номер 51(3)

Опубликована: Март 1, 2023

Insulin resistance (IR) and cardiovascular disease (CVD) represent two universal public health hazards, especially in today’s Western societies. A causal-effect relationship has been established that links IR with CVD. The mediating mechanisms are perplexing, under ongoing, rigorous investigation remain to be fully elucidated. is a condition encompassing hyperglycemia compensatory hyperinsulinemia. It occurs when insulin not capable of exerting its maximum effects on target tissues, including skeletal muscles, liver adipose tissue. This alteration signaling pathways results the development cardiometabolic disorders, obesity, dyslipidemia, low-grade inflammation, endothelial dysfunction hypertension, all which predisposing factors for atherosclerosis management can achieved through dietary modifications, inclusion regular exercise routines everyday life, pharmacological agents other interventions tailored each individual patient’s needs. important underline though that, although various antidiabetic drugs may improve available, no medications as yet specifically approved treatment IR. narrative review will focus current scientific clinical evidence pertaining IR, connecting CVD, well plausible strategies holistic, personalized approach management.

Язык: Английский

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