Association of NFκβ, TNFα, IL-6, IL-1β, and LPL Polymorphisms with Type 2 Diabetes Mellitus and Biochemical Parameters in a Mexican Population

Luo

The Kaohsiung J of Med Scie

et al. 2022

Hyperglycemia is the most important factor leading to the complications of type 2 diabetes mellitus (T2DM). The primary condition for the treatment of T2DM is to change the glucose and lipid metabolism disorders in the liver and other insulin-sensitive tissues. The current study aims to unearth the potential molecular mechanism of inhibiting liver gluconeogenesis to provide a new theoretical basis for the treatment of T2DM. High glucose (HG) induction of HepG2 cells followed by treatment with sequence-similar family 3 member D (FAM3D). Dual specificity phosphatases 1 (DUSP1), zinc finger protein 36 (ZFP36), salt-induced kinase 1 (SIK1), p-SIK1, posphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene and protein expression level were detected by quantitative real-time polymerase chain reaction and western blot. The PEPCK and G6Pase activities were detected by enzyme linked immunosorbent assay.Glucose production assay to determine glucose content. The RNA binding protein immunoprecipitation assay was used to detect the binding of ZFP36 to SIK1. FAM3D facilitated the expression of DUSP1 but suppressed the expression of gluconeogenesis-related factors in an HG environment. The expression of ZFP36 was up-regulated in an HG environment. ZFP36 could reverse the inhibition of gluconeogenesis caused by FAM3D. HG-induced upregulation of ZFP36 was downregulated by overexpression of DUSP1. ZFP36 bound to SIK1, and downregulation of ZFP36 promoted SIK1 expression and inhibits gluconeogenesis. Our study demonstrated FAM3D inhibited gluconeogenesis through the DUSP1/ ZFP36/SIK1 axis in an HG environment, which provided a new theoretical basis for exploring the pathogenesis and treatment strategy of T2DM.

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

FAM3D inhibits gluconeogenesis in high glucose environment via DUSP1/ZFP36/SIK1 axis

Luo

The Kaohsiung J of Med Scie

et al. 2022

“…The results of early animal model studies of T2DM showed a large number of white blood cell aggregates in retinal macular cells and a significant increase in several inflammatory factors, including interleaves and TNF- α [ 12 ]. A comparative study of T2DM patients undergoing hysterectomy found that IL-1 β and TNF- α were significantly elevated in vitreous bodies without proliferative homeopathy, confirming the role of inflammatory factors in developing DR [ 13 ]. There are two types of IL-1, IL-1 α , and IL-1 β , and IL-1 in the blood is mainly IL-1 β secreted by monocycle and esophageal.…”

Section: Discussionmentioning

confidence: 98%

Expression of TNF-α and IL-1β in Peripheral Blood of Patients with T2DM Retinopathy

Qian

Computational and Mathematical Methods in Medicine

2022

Aims. The expression and clinical significance of tumor necrosis factor-α (INF-α) and interleukin 1-β (IL-1β) in retinal cells of patients with type 2 diabetes (T2DM) retinopathy were detected by flow cytometry. Materials and Methods. Fifty patients with T2DM who attended our ophthalmology clinic between May 2021 and May 2022 were selected as the observation group. Another 50 healthy individuals who were examined at our hospital during the same period were selected as the comparison group. Tear film rupture time (BUT), fluorescein staining (FL), basal tear secretion (Schirmer I) test, and conjunctival impression cytology (CIC) were detected in both groups, and the expression of TNF-α and IL-1β in retinal cells was observed by immunohistochemical staining. Results. The levels of IL13 and TNF-α in the two groups were not exactly the same. The serum levels of IL13 and TNF-α in the observation group were significantly higher than those in the control group, and there was a statistically significant difference ( P < 0.05 ). TNF-α and IL-1B expressions in the observation group were positively correlated with the fluorescence staining, and the expression of TNF-α and IL-1β in the observation group was significantly negatively correlated with the BUT test and Schirmer I test. Conclusion. Serums TNF-α and IL-1β are significantly elevated in patients with T2DM retinopathy and gradually increase with disease progression. Combined detection of serums TNF-α and IL-1β can help determine the severity of the disease and assess the prognosis.

Diabetes Obesity Metabolism

“…29,30 There was an additive effect of the polymorphisms of LPL rs285 alongside those genes reflecting chronic inflammation (including NFκβ, IL-6, IL-1β and TNFα genes) that considerably increased the risk of developing T2D. 31 Patients homozygous for the allele + of HindIII showed a significantly faster decline of GFR and a higher increase of albuminuria (both P = .0001), even after adjustment for cholesterol levels and anthropometric variables. 32 In hypercholesterolaemic T2D patients with microalbuminuria, the renal disease has an accelerated course, particularly in those carrying the H +/H+ genotype of the HindIII polymorphism at the LPL locus.…”

Section: Discussionmentioning

confidence: 99%

Variants within the LPL gene confer susceptility to diabetic kidney disease and rapid decline in kidney function in Chinese patients with type 2 diabetes

Cheng

et al. 2023

AimTo examine the association between lipoprotein lipase (LPL) polymorphisms and susceptibility to diabetic kidney disease (DKD) and early renal function decline in Chinese patients with type 2 diabetes (T2D).MethodsThe association of eight LPL single nucleotide polymorphisms (SNPs) with DKD was analysed in 2793 patients with T2D from the third China National Stroke Registry. DKD was defined as either an urine albumin‐to‐creatinine ratio (UACR) of 30 mg/g or higher at baseline and 3 months, or an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 at baseline and 3 months. Rapid decline in kidney function (RDKF) was defined as a reduction in the eGFR of 3 mL/min/1.73 m2 or greater per year. Logistic regression models were used to evaluate the association of LPL SNP and DKD with an additive model.ResultsThe SNPs rs285 C>T (OR = 1.40, P = .0154), rs328 C>G (OR = 2.24, P = .0104) and rs3208305 A>T (OR = 1.85, P = .0015) were identified to be significantly associated with DKD defined by eGFR. Among 1241 participants with follow‐up data, 441 (35.5%) showed RDKF over a mean follow‐up period of 1 year, and the rs285 C allele was associated with higher odds of RDKF (OR = 1.31, 95% CI 1.04‐1.66; P = .025) after adjustment for multiple variables.ConclusionsThese results suggest that LPL‐related SNPs are new candidate factors for conferring susceptibility to DKD and may promote rapid loss of renal function in Chinese patients with T2D.