scholarly journals Intracellular Toxic Advanced Glycation End-Products in 1.4E7 Cell Line Induce Death with Reduction of Microtubule-Associated Protein 1 Light Chain 3 and p62

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 332
Author(s):  
Takanobu Takata ◽  
Akiko Sakasai-Sakai ◽  
Masayoshi Takeuchi
Keyword(s):  
Cell Line ◽  
Advanced Glycation End Products ◽  
Light Chain ◽  
Serum Levels ◽  
Advanced Glycation ◽  
Β Cells ◽  
Physiological Concentration ◽  
Glycation End Products ◽  
End Products

Background: The death of pancreatic islet β-cells (β-cells), which are the insulin-producing cells, promote the pathology in both Type 1 and Type 2 diabetes mellitus (DM) (T1DM and T2DM), and they are protected by autophagy which is one of the mechanisms of cell survival. Recently, that some advanced glycation end-products (AGEs), such as methylglyoxial-derived AGEs and Nε-carboxymethyllysine, induced the death of β-cells were revealed. In contrast, we had reported AGEs derived from glyceraldehyde (GA, the metabolism intermediate of glucose and fructose) are considered to be toxic AGEs (TAGE) due to their cytotoxicity and role in the pathogenesis of T2DM. More, serum levels of TAGE are elevated in patients with T1 and T2DM, where they exert cytotoxicity. Aim: We researched the cytotoxicity of intracellular and extracellular TAGE in β-cells and the possibility that intracellular TAGE were associated with autophagy. Methods: 1.4E7 cells (a human β-cell line) were treated with GA, and analyzed viability, quantity of TAGE, microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, and p62. We also examined the viability of 1.4E7 cells treated with TAGE-modified bovine serum albumin, a model of TAGE in the blood. Results: Intracellular TAGE induced death of 1.4E7 cells, decrease of LC3-I, LC3-II, and p62. Extracellular TAGE didn’t show cytotoxicity in the physiological concentration. Conclusion: Intracellular TAGE induced death of β-cells more strongly than extracellular TAGE, and may suppress autophagy via reduction of LC3-I, LC3-II, and p62 to inhibit the degradation of them.

scholarly journals Relationship Between Advanced Glycation End Products and Their Receptor, sRAGE and Cardiovascular Diseases Risk in Adults with T2D and Vitamin D Insufficiency/deficiency (FS12-08-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Justina Owusu ◽  
Fatma Huffman ◽  
Juan Liuzzi ◽  
Tan Li ◽  
Vijaya Narayanan
Keyword(s):  
Blood Pressure ◽  
Vitamin D ◽  
Cardiovascular Diseases ◽  
Advanced Glycation End Products ◽  
Serum Levels ◽  
Vitamin D Insufficiency ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
The Relationship

Abstract Objectives Advanced Glycation End Products, (AGEs) and their soluble receptor (sRAGE) have been implicated in the development of complications and mortality among individuals with type 2 diabetes (T2D). There is limited information on the relationship between AGEs and sRAGE and risk of cardiovascular diseases (CVD) in minority groups, who have a higher burden of T2D. The relationship between AGEs and sRAGE and CVD risks in adults with T2D and vitamin D insufficiency/deficiency was assessed in a minority population. Methods A cross sectional study of Hispanics and African Americans with T2D (n = 64, 41 women and 23 men, mean age = 54 ± 9) recruited from two clinics in Miami Dade. Systolic (SBP) and diastolic blood pressure (DBP), weight and height measurement and serum lipid profile were completed. ELISA kits were used to assess serum levels of AGEs (Biotang Inc/TSZ Elisa, Waltham, MA, USA) and sRAGE (Biotang Inc/TSZ Elisa, Waltham, MA, USA). Multiple linear regression was used to assess association between AGEs, sRAGE and CVD risks. Results A negative and significant association between AGEs and high-density lipoprotein cholesterol (HDL-C)(B = −0.551, P = 0.029) was found. The relationship between AGEs and HDL-C persisted after adjusting for covariates (P < 0.05). sRAGE was significantly associated with SBP (B = 0.015, P = 0.025) and diastolic blood pressure DBP (B = 0.0271, P = 0.037). Results loss significance when association between sRAGE and DBP and SBP were adjusted for covariates such as age, body mass index (BMI), smoking and alcohol intake. Conclusions Our results suggest that AGEs and sRAGE are related to markers of cardiovascular risk such as HDL-C, SBP and DBP in the study population of African Americans and Hispanics with T2D and vitamin D insufficiency/deficiency. Measures on reducing serum levels of AGEs and improving sRAGE and vitamin D are warranted in these populations for risk reduction of CVD. Funding Sources Partial funding for this research was provided through an NIH/NIDDK sponsored grant.

scholarly journals Higher levels of the soluble receptor for advanced glycation end products and lower levels of the extracellular newly identified receptor for advanced glycation end products were associated with lipid-lowering drugs in patients with type 1 diabetes: a comparative cross-sectional study

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Eva O. Melin ◽  
Jonatan Dereke ◽  
Magnus Hillman
Keyword(s):  
Type 1 Diabetes ◽  
Advanced Glycation End Products ◽  
Inflammatory Responses ◽  
Lipid Lowering ◽  
Advanced Glycation ◽  
Cross Sectional ◽  
Lipid Lowering Drugs ◽  
Glycation End Products ◽  
End Products

Abstract Background The receptors for advanced glycation end products (RAGE) are increased in atherosclerotic plaques. Soluble (s)RAGE decreases, whereas the extracellular newly identified receptor for advanced glycation end products (EN-RAGE) increases inflammatory responses mediated by RAGE. The aims were to explore whether sRAGE, EN-RAGE and the EN-RAGE/sRAGE ratio, were associated with the use of lipid-lowering drugs (LLD) and/or antihypertensive drugs (AHD) in patients with type 1 diabetes (T1D). Methods Cross-sectional design. T1D patients were consecutively recruited from one diabetes clinic. Blood samples were collected, supplemented with data from electronic health records. sRAGE and EN-RAGE were analysed by enzyme linked immunosorbent assays. An EN-RAGE/sRAGE ratio was calculated. Adjustments were performed with inflammatory and metabolic variables, s-creatinine, depression, smoking, physical inactivity, medication, and cardiovascular complications. Multiple regression analyses were performed. Results In this study 283 T1D patients (men 56%, 18–59 years) were included. One-hundred and thirty LLD users compared to 153 non-users had lower levels of the EN-RAGE/sRAGE ratio (P = 0.009), and 89 AHD users compared to 194 non-users had lower levels of sRAGE (P = 0.031). The use of LLD (inversely) (B coefficient − 0.158, P = 0.033) and the use of AHD (B coefficient 0.187, P = 0.023) were associated with the EN-RAGE/sRAGE ratio. sRAGE (Lg10) (per unit) (adjusted odds ratio (AOR) = 3.5, 95% CI = 1.4–9.1, P = 0.009), EN-RAGE (Lg10) (per unit) (inversely) (AOR 0.4, 95% CI = 0.2–1.0, P = 0.046), age (P <  0.001), and triglycerides (P <  0.029), were associated with LLD. sRAGE (Lg10) (per unit) (inversely) (AOR = 0.2, 95% CI = 0.1–0.5, P = 0.001), diabetes duration, triglycerides, s-creatinine, and systolic BP (all P values < 0.043), were associated with AHD. Conclusions Higher sRAGE levels and lower EN-RAGE levels were linked to the use of LLD, whereas lower sRAGE levels were linked to the use of AHD. No other variables but the use of LLD and the use of AHD were linked to the EN-RAGE/sRAGE ratio. This may be of major importance as sRAGE is an inhibitor and EN-RAGE is a stimulator of inflammatory processes mediated by RAGE.

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