Dietary advanced glycated end-products and medicines influence the expression of SIRT1 and DDOST in peripheral mononuclear cells from long-term type 1 diabetes patients

Abstract

Quantitative polymerase chain reaction was employed to quantify expression of two genes coding for advanced glycation end-product receptors [RAGE ( AGER) and AGER1 ( DDOST)] and of the gene coding the deacetylase SIRT1 ( SIRT1) in peripheral blood mononuclear cells from type 1 diabetes patients without [Group A, n = 35; 28.5 (24-39) years old; median (interquartile interval)] or with at least one microvascular complication [Group B, n = 117; 34.5 (30-42) years old]; 31 healthy controls were also included. In a subgroup of 48 patients, daily advanced glycation end-products intake before blood collection was assessed. Lower expression of DDOST was found in patients than in controls after adjustment for sex, age, use of statins, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Higher expressions of AGER, DDOST and SIRT1 were observed in Group A. Stratifying by complications, AGER and DDOST expressions were higher in those without retinopathy and without diabetic kidney disease, respectively, compared to patients with these complications. Patients using statins or angiotensin receptor blockers presented higher expression of DDOST. Expression of SIRT1 was higher in patients consuming ≥12,872 KU daily of advanced glycation end-products. Although AGER, DDOST and SIRT1 are differently expressed in peripheral blood mononuclear cells from type 1 diabetes patients with and without microvascular complications, they are also influenced by dietary advanced glycation end-products and by statins and angiotensin receptor blockers.

Leukotriene Pathway Activation Associates with Poor Glycemic Control and with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes

“…Peripheral blood was collected into BD Vacutainer CPT tubes (BD, Franklin Lakes, NJ, USA) after a 12 h fasting period. The Ficoll method was employed to isolate PBMC, as previously described [15] and plasma was stored at -80°C for further measurements. Total RNA was extracted by the RNeasy Mini Kit (Qiagen, Germantown, MD, USA) after PBMC lysis with RNA quantification was performed by NanoDrop (ND-1000 Spectrophotometer), and the integrity of total RNA was assessed by 1% agarose gel electrophoresis.…”

“…Using the StepOnePlus Real-Time PCR System (Life Technologies), mRNA expressions of the following genes were evaluated: LTB4R, ALOX5, and MYD88. Additionally, the expressions of the three genes previously evaluated in this cohort of individuals were correlated with the expressions of LTB4R, ALOX5, and MYD88: DDOST (encodes AGE-R1), AGER (encodes RAGE), and SIRT1 (encodes sirtuin-1) [15]. Quantitative PCR was performed as follows: 10 μL of TaqMan Gene Expression Master Mix (Life Technologies), 1 μL of hydrolysis probe set, 10 ng of cDNA, and 7 μL of RNase free H 2 O were mixed.…”

“…Analysis in Plasma. Plasmatic thiobarbituric acidreactive substances (TBARS) and reduced glutathione (GSH) were measured in all participants of this study, as pre-viously described [15]. LTB4 was measured by the EIA kit (Cayman Chemical, MI, USA), according to the manufacturer's instructions.…”

Advanced Glycated apoA-IV Loses Its Ability to Prevent the LPS-Induced Reduction in Cholesterol Efflux-Related Gene Expression in Macrophages

“…Ddost encodes for AGER1, an AGE receptor whose expression is induced during glycoxidative and inflammatory stress allowing antagonism to the deleterious signaling of the AGE-RAGE axis [68]. In this investigation, we found reduction in Ddost mRNA levels in cells preincubated with unmodified and AGE-apoA-IV prior to LPS.…”

Globally elevating the AGE clearance receptor, OST48, does not protect against the development of diabetic kidney disease, despite improving insulin secretion

“…OST48 gene and protein expression are decreased by diets abundantly rich in AGEs 19 and by diabetes 20,21 . In addition, there are associations between lower OST48 levels in circulating immune cells and progressive diabetic nephropathy in a small cohort of patients with type 1 diabetes 22,23 and with impaired insulin sensitivity patients with in type 2 diabetes 24,25 . To date, there has been one, in vivo investigation using untargeted over-expression of OST48.…”