PMID- 33442388 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210115 IS - 1664-042X (Print) IS - 1664-042X (Electronic) IS - 1664-042X (Linking) VI - 11 DP - 2020 TI - Patterns of Toll-Like Receptor Expressions and Inflammatory Cytokine Levels and Their Implications in the Progress of Insulin Resistance and Diabetic Nephropathy in Type 2 Diabetic Patients. PG - 609223 LID - 10.3389/fphys.2020.609223 [doi] LID - 609223 AB - Background: Diabetic nephropathy (DNP) is a type 2 diabetes mellitus (T2DM) chronic complication, which is the largest single cause of end-stage kidney disease. There is an increasing evidence of the role of inflammation and Toll-like receptors (TLRs) as part of innate immune system in its development and progression. In addition, Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) downward signaling causes the production of proinflammatory cytokines, which can induce insulin (INS) resistance in T2DM. Objective: The goal of this study was to estimate the expression of TLRs (TLR2 and TLR4) in relation to inflammation and INS resistance in nephrotic type 2 diabetic patients with or without renal failure and to discuss the role of these TLRs in DNP progression. Patients and Methods: In this study, blood samples were obtained from type 2 diabetic patients with or without renal failure, and patients with non-diabetic renal failure were compared to healthy controls. All participants were tested for analysis of fasting plasma glucose and serum insulin, kidney function tests, C-reactive protein (CRP), and proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interleukin 6 (IL-6) as well as expression of TLR2 and TLR4 in peripheral blood (PB). Statistical analysis of data was done by using SPSS. Results: Diabetic patients with renal failure exhibited significant increase in TLR2, TLR4 mRNA expression in PB in comparison with normal subjects, diabetic patients without renal failure and non-diabetic patients with renal failure. Both diabetic patients with or without kidney failure and non-diabetic patients with renal failure had increased TLR2 and TLR4 mRNA expression in association with increased levels of proinflammatory cytokines (TNF-alpha, IFN-gamma, and IL-6) compared to normal subjects. The diabetic patients with kidney failure exhibited the highest elevation of TLRs, Th1 cytokines and CRP in association the highest record of insulin resistance. Conclusion: Toll-like receptor 2 and Toll-like receptor 4 increased expression and Th2 cytokines may have an important role in the progression of DNP and deteriorations in insulin resistance in type 2 diabetic patients. Therefore, TLR2 and TLR4 may be a promising therapeutic target to prevent or retard DNP in type 2 diabetic patients. CI - Copyright (c) 2020 Aly, Ahmed, Hozayen, Rabea, Ali, El Askary and Ahmed. FAU - Aly, Rofyda H AU - Aly RH AD - Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt. FAU - Ahmed, Amr E AU - Ahmed AE AD - Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt. FAU - Hozayen, Walaa G AU - Hozayen WG AD - Biochemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt. FAU - Rabea, Alaa Mohamed AU - Rabea AM AD - Internal Medicine Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt. FAU - Ali, Tarek M AU - Ali TM AD - Department of Physiology, College of Medicine, Taif University, Taif, Saudi Arabia. AD - Department of Physiology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt. FAU - El Askary, Ahmad AU - El Askary A AD - Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia. AD - Department of Medical Biochemistry, Faculty of Medicine (New Damietta), Al Azhar University, Cairo, Egypt. FAU - Ahmed, Osama M AU - Ahmed OM AD - Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt. LA - eng PT - Journal Article DEP - 20201223 PL - Switzerland TA - Front Physiol JT - Frontiers in physiology JID - 101549006 PMC - PMC7798354 OTO - NOTNLM OT - Toll-like receptors OT - diabetes mellitus OT - inflammatory cytokines OT - insulin resistance OT - kidney failure COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/01/15 06:00 MHDA- 2021/01/15 06:01 PMCR- 2020/12/23 CRDT- 2021/01/14 05:47 PHST- 2020/09/22 00:00 [received] PHST- 2020/12/04 00:00 [accepted] PHST- 2021/01/14 05:47 [entrez] PHST- 2021/01/15 06:00 [pubmed] PHST- 2021/01/15 06:01 [medline] PHST- 2020/12/23 00:00 [pmc-release] AID - 10.3389/fphys.2020.609223 [doi] PST - epublish SO - Front Physiol. 2020 Dec 23;11:609223. doi: 10.3389/fphys.2020.609223. eCollection 2020.