The Increased Expression of Regulator of G-Protein Signaling 2 (RGS2) Inhibits Insulin-Induced Akt Phosphorylation and Is Associated with Uncontrolled Glycemia in Patients with Type 2 Diabetes

Abstract

Experimental evidence in mice models has demonstrated that a high regulator of G-protein signaling 2 (RSG2) protein levels precede an insulin resistance state. In the same context, a diet rich in saturated fatty acids induces an increase in RGS2 protein expression, which has been associated with decreased basal metabolism in mice; however, the above has not yet been analyzed in humans. For this reason, in the present study, we examined the association between RGS2 expression and insulin resistance state. The incubation with palmitic acid (PA), which inhibits insulin-mediated Akt Ser473 phosphorylation, resulted in the increased RGS2 expression in human umbilical vein endothelial-CS (HUVEC-CS) cells. The RGS2 overexpression without PA was enough to inhibit insulin-mediated Akt Ser473 phosphorylation in HUVEC-CS cells. Remarkably, the platelet RGS2 expression levels were higher in type 2 diabetes mellitus (T2DM) patients than in healthy donors. Moreover, an unbiased principal component analysis (PCA) revealed that RGS2 expression level positively correlated with glycated hemoglobin (HbA1c) and negatively with age and high-density lipoprotein cholesterol (HDL) in T2DM patients. Furthermore, PCA showed that healthy subjects segregated from T2DM patients by having lower levels of HbA1c and RGS2. These results demonstrate that RGS2 overexpression leads to decreased insulin signaling in a human endothelial cell line and is associated with poorly controlled diabetes.

Coconut products alleviate hyperglycaemic, hyperlipidimic and nephropathy indices in streptozotocin-induced diabetic wistar rats

“…T2DM is characterised by chronically increased glucose levels. Under normal physiological conditions, glucose levels are regulated by insulin levels, however this regulation is derailed in T2DM resulting from reduced insulin secretion or resistance to insulin ( Vazquez-Jimenez et al 2021 ). Besides, dysregulated glucose and insulin levels, there are increased glycated haemoglobin levels in red blood cells (RBCs) of persons with T2DM due to increased circulating glucose levels ( González-Ortiz et al, 2012 ).…”

Ponicidin attenuates streptozotocin‐induced diabetic nephropathy in rats via modulating hyperlipidemia, oxidative stress, and inflammatory markers

“…The glucose level was mainly regulated by the insulin in normal physiological conditions, on the other hand, this regulation is disrupted in the case of DM, which is resulting from decreased insulin generation or resistance. [ 32 ] Several clinical trials discovered that the initiation and progression of DN could be delayed by strict diabetic control. [ 33 ] Here we witnessed that the ponicidin treatment suppressed the glucose and HOMA‐IR levels in the STZ‐provoked DN animals.…”

Identification of biomarkers and pathways for focal segmental glomerulosclerosis using next generation sequencing data and bioinformatics analysis

“…Pathways include metabolism [42], transport of small molecules [43] and immune system [44] are linked with progression of FSGS. PDK4 [45], ALB (albumin) [46], EGR1 [47], RYR3 [48], APOH (apolipoprotein H) [49], CYP27B1 [50], ESM1 [51], GATA6 [52], PCK1 [53], TET2 [54], AFP (alpha fetoprotein) [55], CACNA1D [56], ATF3 [57], EGF (epidermal growth factor) [58], LPL (lipoprotein lipase) [59], PPARGC1A [60], PLG (plasminogen) [61], NR4A1 [62], STRA6 [63], MLXIPL (MLX interacting protein like) [64], PLA2G6 [65], RGS2 [66], GPS2 [67], SOX5 [68], GLUL (glutamate-ammonia ligase) [69], RYK (receptor like tyrosine kinase) [70], NFKBIA (NFKB inhibitor alpha) [71], LGR4 [72], SPRY2 [73], TRPC1 [74], KL (klotho) [75], GCLC (glutamate-cysteine ligase catalytic subunit) [76], NOX4 [77], CD69 [78], SLC19A2 [79], S100A12 [80], MT1A [81], SORCS1 [82], FKBP5 [83], AFM (afamin) [84], CA3 [85], MAOA (monoamine oxidase A) [86], ND1 [87], ATP6 [88], CHGA (chromogranin A) [89], ICOS (inducible T cell costimulator) [90], DBH (dopamine beta-hydroxylase) [91], CD5 [92], LTA (lymphotoxin alpha) [93], IFNG (interferon gamma) [94], MPO (myeloperoxidase) [95], CD70 [96], CD300E [97], COLEC12 [98], TLR10 [99], LCN2 [100], SLAMF7 [101], TREM2 [102], ITGAL (integrin subunit alpha L) [103], CD27 [104], JAK3 [105], CCR5 [106], FCN1 [107], IL1RN [108], CX3CR1 [109], PDCD1 [110], TRPM2 [111], PLEK (pleckstrin) [112], CD101 [113],...…”

“…The GO [64], PLA2G6 [65], RGS2 [66], GPS2 [67], SOX5 [68], GLUL (glutamate-ammonia ligase) [69], RYK (receptor like tyrosine kinase) [70], NFKBIA (NFKB inhibitor alpha) [71], LGR4 [102], ITGAL (integrin subunit alpha L) [103], CD27 [104], JAK3 [105], CCR5 [106], FCN1 [107], IL1RN [108], CX3CR1 [109], PDCD1 [110], TRPM2 [111], PLEK (pleckstrin) [112], CD101 [113], TNF (tumor necrosis factor) [114], CD48 [115], ALOX5 [116], TLR7 [117], CCL3 [118], C2 [119], TNFRSF1B [120], CCR2 [121], PLA2G7 [122], TH (tyrosine hydroxylase) [123], WNT7A [124], ADRB3 [125], GPBAR1 [126], SLC6A20 [127], FUT2 [128], ANK1 [129], NOS3 [130], APLNR (apelin receptor) [131], COMP (cartilage oligomeric matrix protein) [132], RETN (resistin) [133], NMU (neuromedin U) [134], S100B [135], IGFBP1 [136], COL1A1 [137], HBB (hemoglobin subunit beta) [138] and PLAC8 [139] genes plays important regulatory roles in diabetes mellitus. Various genes such as PDK4 [140], ALB (albumin) [141], EGR1 [142], RYR3 [48], CYP27B1 [143], GATA6 [144], NR4A3 [145], TET2…”