Molecular and cellular mechanisms in diabetic heart failure: Potential therapeutic targets

Mengstie, Misganaw Asmamaw; Abebe, Endeshaw Chekol; Teklemariam, Awgichew Behaile; Mulu, Anemut Tilahun; Teshome, Assefa Agegnehu; Zewde, Edgeit Abebe; Muche, Zelalem Tilahun; Azezew, Muluken Teshome

doi:10.3389/fendo.2022.947294

Cited by 6 publications

(3 citation statements)

References 127 publications

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“…Diabetes can cause multiple complications, including cardiovascular diseases and organ failure [ 248 ]. Diabetic cardiomyopathy (DCM) is one of the major causes of death in diabetic patients, and there is no specific treatment strategy [ 249 ].…”

Section: Sting-related Diseasesmentioning

confidence: 99%

Potential Therapeutic Value of the STING Inhibitors

2023

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The stimulator of interferon genes (STING) is a critical protein in the activation of the immune system in response to DNA. It can participate the inflammatory response process by modulating the inflammation-preferred translation program through the STING-PKR-like endoplasmic reticulum kinase (PERK)-eIF2α pathway or by inducing the secretion of type I interferons (IFNs) and a variety of proinflammatory factors through the recruitment of TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) or the regulation of the nuclear factor kappa-B (NF-κB) pathway. Based on the structure, location, function, genotype, and regulatory mechanism of STING, this review summarizes the potential value of STING inhibitors in the prevention and treatment of infectious diseases, psoriasis, systemic lupus erythematosus, non-alcoholic fatty liver disease, and other inflammatory and autoimmune diseases.

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Section: Sting-related Diseasesmentioning

confidence: 99%

Potential Therapeutic Value of the STING Inhibitors

2023

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“…Currently, DM incidence is skyrocketing in response to high‐caloric food diets and sedentary lifestyles (Carpino & Goodwin, 2010). Diabetic patients are usually identified as one of two forms of diabetes including insulin‐dependent DM (IDDM; type 1‐DM) and insulin‐independent DM (NIDDM; type 2‐DM) (Mengstie et al, 2022). Type 1 DM is juvenile diabetes in which the pancreas fails to create insulin due to autoimmune β‐cell destruction (Riaz, 2015).…”

Section: Introductionmentioning

confidence: 99%

Polysaccharides (pectin, mucilage, and fructan inulin) and their fermented products: A critical analysis of their biochemical, gut interactions, and biological functions as antidiabetic agents

El‐Nashar,

Taleb,

EL‐Shazly

et al. 2023

Phytotherapy Research

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Diabetes mellitus is a globally metabolic endocrine syndrome marked by a deficiency of insulin secretion (type‐1 DM) or glucose intolerance arising from insulin response impairment (type‐2 DM) leading to abnormal glucose metabolism. With an increasing interest in natural dietary components for diabetes management, the identification of novel agents witnessed major discoveries. Plant‐derived mucilage, pectin, and inulin are important non‐starch polysaccharides that exhibit effective antidiabetic properties often termed soluble dietary fiber (SDF). SDF affects sugar metabolism through multiple mechanisms affecting glucose absorption and diffusion, modulation of carbohydrate metabolizing enzymes (α‐amylase and α‐glucosidase), ameliorating β‐pancreatic cell dysfunction, and improving insulin release or sensitivity. Certain SDFs inhibit dipeptidyl peptidase‐4 and influence the expression levels of genes related to glucose metabolism. This review is designed to discuss holistically and critically the antidiabetic effects of major SDF and their underlying mechanisms of action. This review should aid drug discovery approaches in developing novel natural antidiabetic drugs from SDF.

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“…Furthermore, it permits to assess contractile reserve by subjecting papillary muscles to positive inotropic stimulation. As myocardial metabolism is changed in DM [ 28 , 29 ] and gliflozins may improve metabolism [ 30 , 31 ], we analyzed the activity of key enzymes involved in myocardial energy metabolism and myocardial metabolomics.…”

Section: Introductionmentioning

confidence: 99%

The influence of dapagliflozin on cardiac remodeling, myocardial function and metabolomics in type 1 diabetes mellitus rats

Rodrigues,

Rosa,

Campos

et al. 2023

Diabetol Metab Syndr

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Background Sodium-glucose cotransporter (SGLT)2 inhibitors have displayed beneficial effects on the cardiovascular system in diabetes mellitus (DM) patients. As most clinical trials were performed in Type 2 DM, their effects in Type 1 DM have not been established. Objective To evaluate the influence of long-term treatment with SGLT2 inhibitor dapagliflozin on cardiac remodeling, myocardial function, energy metabolism, and metabolomics in rats with Type 1 DM. Methods Male Wistar rats were divided into groups: Control (C, n = 15); DM (n = 15); and DM treated with dapagliflozin (DM + DAPA, n = 15) for 30 weeks. DM was induced by streptozotocin. Dapagliflozin 5 mg/kg/day was added to chow. Statistical analysis: ANOVA and Tukey or Kruskal-Wallis and Dunn. Results DM + DAPA presented lower glycemia and higher body weight than DM. Echocardiogram showed DM with left atrium dilation and left ventricular (LV) hypertrophy, dilation, and systolic and diastolic dysfunction. In LV isolated papillary muscles, DM had reduced developed tension, +dT/dt and -dT/dt in basal condition and after inotropic stimulation. All functional changes were attenuated by dapagliflozin. Hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) activity was lower in DM than C, and PFK and PK activity higher in DM + DAPA than DM. Metabolomics revealed 21 and 5 metabolites positively regulated in DM vs. C and DM + DAPA vs. DM, respectively; 6 and 3 metabolites were negatively regulated in DM vs. C and DM + DAPA vs. DM, respectively. Five metabolites that participate in cell membrane ultrastructure were higher in DM than C. Metabolites levels of N-oleoyl glutamic acid, chlorocresol and N-oleoyl-L-serine were lower and phosphatidylethanolamine and ceramide higher in DM + DAPA than DM. Conclusion Long-term treatment with dapagliflozin attenuates cardiac remodeling, myocardial dysfunction, and contractile reserve impairment in Type 1 diabetic rats. The functional improvement is combined with restored pyruvate kinase and phosphofructokinase activity and attenuated metabolomics changes.

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Molecular and cellular mechanisms in diabetic heart failure: Potential therapeutic targets

Cited by 6 publications

References 127 publications

Potential Therapeutic Value of the STING Inhibitors

Potential Therapeutic Value of the STING Inhibitors

Polysaccharides (pectin, mucilage, and fructan inulin) and their fermented products: A critical analysis of their biochemical, gut interactions, and biological functions as antidiabetic agents

The influence of dapagliflozin on cardiac remodeling, myocardial function and metabolomics in type 1 diabetes mellitus rats

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