scholarly journals Targets and Candidate Agents for Type 2 Diabetes Treatment with Computational Bioinformatics Approach

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Qiong Wang ◽  
Zhigang Zhao ◽  
Jing Shang ◽  
Wei Xia
Keyword(s):  
Type 2 Diabetes ◽  
Growth Factor ◽  
Small Molecules ◽  
Transforming Growth Factor Beta ◽  
Drug Targets ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Type 2 Diabetes Treatment ◽  
Systematic Understanding

We sought to explore the molecular mechanism of type 2 diabetes (T2D) and identify potential drug targets and candidate agents for T2D treatment. The differentially expressed genes (DEGs) were assessed between human pancreatic islets with T2D and normal islets. The dysfunctional pathways, the potential transcription factor, and microRNA targets were analyzed by bioinformatics methods. Moreover, a group of bioactive small molecules were identified based on the connectivity map database. The pathways of Eicosanoid Synthesis, TGF-beta signaling pathway, Prostaglandin Synthesis and Regulation, and Integrated Pancreatic Cancer Pathway were found to be significantly dysregulated in the progression of T2D. The genes ofZADH2(zinc binding alcohol dehydrogenase domain containing 2),BTBD3(BTB (POZ) domain containing 3), Cul3-based ligases,  LTBP1(latent-transforming growth factor beta binding protein 1),PDGFRA(alpha-type platelet-derived growth factor receptor), andFST(follistatin) were determined to be significant nodes regulated by potential transcription factors and microRNAs. Besides, two small molecules (sanguinarine and DL-thiorphan) were identified to be capable of reverse T2D. In the present study, a systematic understanding for the mechanism underlying T2D development was provided with biological informatics methods. The significant nodes and bioactive small molecules may be drug targets and candidate agents for T2D treatment.

scholarly journals Serum transforming growth factor-beta 1 levels in normoalbuminuric and normotensive patients with type 2 diabetes. Effect of metformin and rosiglitazone

HORMONES ◽  
2008 ◽  
Vol 7 (1) ◽  
pp. 70-76 ◽  
Author(s):  
Serkan Yener ◽  
Abdurrahman Comlekci ◽  
Baris Akinci ◽  
Pinar Akan ◽  
Tevfik Demir ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Beta

Thrombospondin-1 (TSP1), Transforming Growth Factor-Beta (TGFb) and Connective Tissue Growth Factor (CTGF) are Involved in the Pathophysiology of Diabetic Retinopathy,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3275-3275
Author(s):  
Raul A. De La Cadena ◽  
Mario C Rico ◽  
Fabiola Del Carpio-Cano ◽  
Fayez Safadi ◽  
Satya P. Kunapuli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Western Blotting ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Control Groups ◽  
Vitreous Fluid ◽  
Growth Factor Beta

Abstract Abstract 3275 Background: Diabetic retinopathy (DR) is a progressive disease that affects over 4 million people in the United States and is one of the leading causes of blindness. The pathophysiology of the early events (no evidence of DR) leading to diabetic retinopathy is still not fully understood. Recent studies have proposed that levels of TSP1 (Arch Ophthalmol 127:507, 2009) and CTGF (Diabetes Care 27:758, 2004) may play a role in shifting the angiogenic balance and pathogenesis of DR. We postulate that during acute and chronic inflammation, as seen in type-2 diabetes a pro-inflammatory axis comprised by TSP1, transforming growth factor-beta (TGF-b) and CTGF may play a significant role in the progression of NPDR to PDR. Methods: This is a prospective control study comprised to date of: a) six (6) human subjects with NPDR, b) eleven (11) subjects with PDR, c) five (5) subjects without type-2 diabetes but in need of pars plana vitrectomy, and d) seventeen (17) normal human volunteers. Plasma samples were obtained from all groups (a-d) after signing an informed consent approved by our institution's IRB committee. Vitreous fluid (VF) was collected from subjects in b and c. Cytokine profile was determined by Multiplex Assay. TSP1, TGF-b and CTGF were assessed by commercially available ELISA assays and visualized by Western-blotting technique. Results: TNFa in conjunction with other pro-inflammatory cytokines was found elevated in NPDR subjects when compared to subjects in control groups (c-d, P<0.05). The evidence of acute inflammation in the NPDR group was not only evident by higher levels of TNFa but also TSP1 and TGF-b when compared to control groups (P<0.002 and P<0.001 respectively). Interestingly, the TSP1 profile seen in the NPDR subjects changed significantly (lower levels) when compared to PDR subjects (P<0.002) and was even significantly different from that one seen in control subjects. This early foot print observed for TSP1 was similar to the IL-4 profile (P<0.003 NPDR vs PDR, P<0.0002 NPDR vs controls) a molecule considered to be anti-angiogenic like TSP1. CTGF plasma levels were increased in PDR subjects in plasma (mean 1.67 + 0.27 SEM pg/ml) when compared to NPDR subjects (0.77 + 0.22 pg/ml, P<0.05) and the levels were also higher in VH of PDR subjects when compared with VH controls subjects. On Western-blotting analysis, CTGF and TSP1 in plasma and in VH showed evidence of proteolytic fragmentation, a phenomenon that has been associated with potential promotion of angiogenesis and fibrosis. Summary: Our findings are in agreement with the proposed hypothesis that TSP1 in systemic circulation or in the micro environment (vitreous fluid) in conjunction with TGF-b represent a pro-inflammatory axis in the disease progression from NPDR to PDR with CTGF as the effector molecule placing this axis as a potential therapeutic intervention to prevent progression of disease and to improve quality of life in patients afflicted by NPDR. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Changes of transforming growth factor beta 1 in patients with type 2 diabetes and diabetic nephropathy

Medicine ◽  
2017 ◽  
Vol 96 (15) ◽  
pp. e6583 ◽  
Author(s):  
Yong-Chao Qiao ◽  
Yin-Ling Chen ◽  
Yan-Hong Pan ◽  
Wei Ling ◽  
Fang Tian ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Beta

scholarly journals Initial Combination Empagliflozin and Linagliptin Improves Kidney Fibrotic Marker in Patients With Type 2 Diabetes: A Randomized Controlled Trial

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A416-A416
Author(s):  
Nattapol Sathavarodom ◽  
Thanaporn Putthanuparp ◽  
Verapon Pinphanichakarn
Keyword(s):  
Type 2 Diabetes ◽  
Growth Factor ◽  
Kidney Disease ◽  
Transforming Growth Factor Beta ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Response To Therapy ◽  
Diabetic Kidney ◽  
Initial Combination

Abstract Background: Transforming growth factor-beta 1 (TGF- ß1) is a novel cytokine marker and also one of the therapeutic targets in the treatment of diabetic kidney disease. Both sodium glucose co-transporter 2 inhibitor and dipeptidyl-peptides 4 inhibitor reduce TGF- ß 1 level in animal studies, but whether it is effective in human is unknown. Objective: To evaluate the effects of combinations of empagliflozin/linagliptin, comparing with empagliflozin alone, in patients with type 2 diabetes. Material and Methods: Subjects are randomized to a combination of empagliflozin 10 mg and linagliptin 5 mg (n = 23), or empagliflozin 10 mg (n = 22) as add-on to standard treatment for 12 weeks. The primary end point is changed from baseline in serum TGF- ß1 at 12 weeks. Results: Among the 45 subjects who completed the study, mean change in TGF-ß1 was -928.2 + 1,204.2 pg/mL, and +206.6 + 592.5 pg/mL in the empagliflozin/linagliptin group and empagliflozin group, respectively (p &lt;0.001). Mean change in estimated glomerular filtration rate (eGFR) increased in the empagliflozin /linagliptin group 4.4 + 7.59 mL/min/1.73m2, whereas mean eGFR decreased in empagliflozin group -0.06 + 11.16 mL/min/1.73m2 (p =0.133). Mean change in HbA1c was -1.3 + 0.6% and -0.4 + 0.6% in empagliflozin/linagliptin and empagliflozin group, respectively (p&lt;0.001). Baseline level of eGFR significantly correlated with baseline TGF- ß1 but did not predict response to therapy. Conclusion: Initial combination empagliflozin and linagliptin may delay progression of kidney fibrosis as early as 12 weeks of treatment. Our study supports that this combination had synergistic action not only glycemic control but also beneficial in kidney protection. Keyword: transforming growth factor - ß1, diabetic kidney disease, combination empagliflozin and linagliptin

scholarly journals LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Carl Herdenberg ◽  
Pascal M. Mutie ◽  
Ola Billing ◽  
Ahmad Abdullah ◽  
Rona J. Strawbridge ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Lipid Metabolism ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Ectopic Expression ◽  
Bmp Signaling ◽  
Null Mouse ◽  
Growth Factor Signaling

AbstractLeucine-rich repeats and immunoglobulin-like domains (LRIG) proteins have been implicated as regulators of growth factor signaling; however, the possible redundancy among mammalian LRIG1, LRIG2, and LRIG3 has hindered detailed elucidation of their physiological functions. Here, we show that Lrig-null mouse embryonic fibroblasts (MEFs) are deficient in adipogenesis and bone morphogenetic protein (BMP) signaling. In contrast, transforming growth factor-beta (TGF-β) and receptor tyrosine kinase (RTK) signaling appeared unaltered in Lrig-null cells. The BMP signaling defect was rescued by ectopic expression of LRIG1 or LRIG3 but not by expression of LRIG2. Caenorhabditis elegans with mutant LRIG/sma-10 variants also exhibited a lipid storage defect. Human LRIG1 variants were strongly associated with increased body mass index (BMI) yet protected against type 2 diabetes; these effects were likely mediated by altered adipocyte morphology. These results demonstrate that LRIG proteins function as evolutionarily conserved regulators of lipid metabolism and BMP signaling and have implications for human disease.

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