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Specialty: Chemistry
Condition: Diabetes
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Total 31 results found since Jan 2013.
Miox in Obesity Molecular Bases of Disease
This study highlights mechanisms concerning the pathobiology of tubular injury in the context of myo-inositol oxygenase (Miox), a tubular enzyme. The kidneys of mice fed a high fat diet (HFD) had increased Miox expression and activity, and the latter was related to phosphorylation of serine/threonine residues. Also, expression of sterol regulatory element-binding protein1 (Srebp1) and markers of cellular/nuclear damage was increased along with accentuated apoptosis and loss of tubular brush border. Similar results were observed in cells treated with palmitate/BSA. Multiple sterol-response elements and E-box motifs were fou...
Source: Journal of Biological Chemistry - January 15, 2016 Category: Chemistry Authors: Tominaga, T., Dutta, R. K., Joladarashi, D., Doi, T., Reddy, J. K., Kanwar, Y. S. Tags: Metabolism Source Type: research
Role of GAPDH/Siah1 Signaling in Pericyte Apoptosis Cell Biology
Diabetic retinopathy (DR) is a leading cause of blindness worldwide, and its prevalence is growing. Current therapies for DR address only the later stages of the disease, are invasive, and have limited effectiveness. Retinal pericyte death is an early pathologic feature of DR. Although it has been observed in diabetic patients and in animal models of DR, the cause of pericyte death remains unknown. A novel pro-apoptotic pathway initiated by the interaction between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the E3 ubiquitin ligase, seven in absentia homolog 1 (Siah1), was recently identified in ocular tissues. In ...
Source: Journal of Biological Chemistry - November 20, 2015 Category: Chemistry Authors: Suarez, S., McCollum, G. W., Jayagopal, A., Penn, J. S. Tags: Cell Biology Source Type: research
PFKFB3 and Insulin Signalling Metabolism
The insulin/insulin-like growth factor (IGF)-1 signaling pathway (ISP) plays a fundamental role in long term health in a range of organisms. Protein kinases including Akt and ERK are intimately involved in the ISP. To identify other kinases that may participate in this pathway or intersect with it in a regulatory manner, we performed a whole kinome (779 kinases) siRNA screen for positive or negative regulators of the ISP, using GLUT4 translocation to the cell surface as an output for pathway activity. We identified PFKFB3, a positive regulator of glycolysis that is highly expressed in cancer cells and adipocytes, as a posi...
Source: Journal of Biological Chemistry - October 23, 2015 Category: Chemistry Authors: Trefely, S., Khoo, P.–S., Krycer, J. R., Chaudhuri, R., Fazakerley, D. J., Parker, B. L., Sultani, G., Lee, J., Stephan, J.–P., Torres, E., Jung, K., Kuiȷl, C., James, D. E., Junutula, J. R., Stockli, J. Tags: Signal Transduction Source Type: research
BiP Co-chaperones and ER Calcium Leakage Membrane Biology
In mammalian cells, signal peptide-dependent protein transport into the endoplasmic reticulum (ER) is mediated by a dynamic polypeptide-conducting channel, the heterotrimeric Sec61 complex. Previous work has characterized the Sec61 complex as a potential ER Ca2+ leak channel in HeLa cells and identified ER lumenal molecular chaperone immunoglobulin heavy-chain-binding protein (BiP) as limiting Ca2+ leakage via the open Sec61 channel by facilitating channel closing. This BiP activity involves binding of BiP to the ER lumenal loop 7 of Sec61α in the vicinity of tyrosine 344. Of note, the Y344H mutation destroys the BiP bind...
Source: Journal of Biological Chemistry - July 23, 2015 Category: Chemistry Authors: Schorr, S., Klein, M.–C., Gamayun, I., Melnyk, A., Jung, M., Schauble, N., Wang, Q., Hemmis, B., Bochen, F., Greiner, M., Lampel, P., Urban, S. K., Hassdenteufel, S., Dudek, J., Chen, X.–Z., Wagner, R., Cavalie, A., Zimmermann, R. Tags: Cell Biology Source Type: research
Tadalafil Integrates NO and H2S Signaling Signal Transduction
Diabetes-induced kidney cell injury involves an increase in matrix protein expression that is only partly alleviated by current treatment, prompting a search for new modalities. We have previously shown that hydrogen sulfide (H2S) inhibits high glucose-induced protein synthesis in kidney podocytes. We tested whether tadalafil, a phosphodiesterase 5 inhibitor used to treat erectile dysfunction, ameliorates high glucose stimulation of matrix proteins by generating H2S in podocytes. Tadalafil abrogated high glucose stimulation of global protein synthesis and matrix protein laminin γ1. Tadalafil inhibited high glucose-induced...
Source: Journal of Biological Chemistry - May 7, 2015 Category: Chemistry Authors: Lee, H. J., Feliers, D., Mariappan, M. M., Sataranatarajan, K., Choudhury, G. G., Gorin, Y., Kasinath, B. S. Tags: Glycobiology and Extracellular Matrices Source Type: research
Zfp407 Regulates Adipose Glucose Uptake Gene Regulation
The glucose transporter GLUT4 facilitates insulin-stimulated glucose uptake in peripheral tissues including adipose, muscle, and heart. GLUT4 function is impaired in obesity and type 2 diabetes leading to hyperglycemia and an increased risk of cardiovascular disease and neuropathy. To better understand the regulation of GLUT4 function, a targeted siRNA screen was performed and led to the discovery that ZFP407 regulates insulin-stimulated glucose uptake in adipocytes. The decrease in insulin-stimulated glucose uptake due to ZFP407 deficiency was attributed to a reduction in GLUT4 mRNA and protein levels. The decrease in GLU...
Source: Journal of Biological Chemistry - March 5, 2015 Category: Chemistry Authors: Buchner, D. A., Charrier, A., Srinivasan, E., Wang, L., Paulsen, M. T., Ljungman, M., Bridges, D., Saltiel, A. R. Tags: Metabolism Source Type: research
Pdx-1 Enhances Transcription of SERCA2b in the Islet {beta} Cell Molecular Bases of Disease
Although the pancreatic duodenal homeobox 1 (Pdx-1) transcription factor is known to play an indispensable role in β cell development and secretory function, recent data also implicate Pdx-1 in the maintenance of endoplasmic reticulum (ER) health. The sarco-endoplasmic reticulum Ca2+ ATPase 2b (SERCA2b) pump maintains a steep Ca2+ gradient between the cytosol and ER lumen. In models of diabetes, our data demonstrated loss of β cell Pdx-1 that occurs in parallel with altered SERCA2b expression, whereas in silico analysis of the SERCA2b promoter revealed multiple putative Pdx-1 binding sites. We hypothesized that Pdx-1 los...
Source: Journal of Biological Chemistry - November 21, 2014 Category: Chemistry Authors: Johnson, J. S., Kono, T., Tong, X., Yamamoto, W. R., Zarain-Herzberg, A., Merrins, M. J., Satin, L. S., Gilon, P., Evans-Molina, C. Tags: Metabolism Source Type: research
Atf3/Pdx-1/Hdac1 Axis Prompts Metabolic Syndrome Gene Regulation
Chronic ethanol consumption induces pancreatic β-cell dysfunction through glucokinase (Gck) nitration and down-regulation, leading to impaired glucose tolerance and insulin resistance, but the underlying mechanism remains largely unknown. Here, we demonstrate that Gck gene expression and promoter activity in pancreatic β-cells were suppressed by chronic ethanol exposure in vivo and in vitro, whereas expression of activating transcription factor 3 (Atf3) and its binding to the putative Atf/Creb site (from −287 to −158 bp) on the Gck promoter were up-regulated. Furthermore, in vitro ethanol-induced Atf3 inhibited the p...
Source: Journal of Biological Chemistry - September 25, 2014 Category: Chemistry Authors: Kim, J. Y., Hwang, J.-Y., Lee, D. Y., Song, E. H., Park, K. J., Kim, G. H., Jeong, E. A., Lee, Y. J., Go, M. J., Kim, D. J., Lee, S. S., Kim, B.-J., Song, J., Roh, G. S., Gao, B., Kim, W.-H. Tags: Molecular Bases of Disease Source Type: research
Insulin, NF-{kappa}B, and Myocardin Signaling in Cardiac Myoblasts Signal Transduction
Hyperinsulinemia contributes to cardiac hypertrophy and heart failure in patients with the metabolic syndrome and type 2 diabetes. Here, high circulating levels of tumor necrosis factor (TNF)-α may synergize with insulin in signaling inflammation and cardiac hypertrophy. We tested whether high insulin affects activation of TNF-α-induced NF-κB and myocardin/serum response factor (SRF) to convey hypertrophy signaling in cardiac myoblasts. In canine cardiac myoblasts, treatment with high insulin (10−8 to 10−7 m) for 0–24 h increased insulin receptor substrate (IRS)-1 phosphorylation at Ser-307, decreased protein leve...
Source: Journal of Biological Chemistry - July 10, 2014 Category: Chemistry Authors: Madonna, R., Geng, Y.-J., Bolli, R., Rokosh, G., Ferdinandy, P., Patterson, C., De Caterina, R. Tags: Gene Regulation Source Type: research
Cystathionine-{gamma}-lyase Activity in Type 1 Diabetes Molecular Bases of Disease
This study investigated the activities of cystathionine-γ-lyase (CSE, the enzyme that catalyzes H2S formation) in livers of type 1 diabetic (T1D) animals and in peripheral blood mononuclear cells (PBMC) isolated from T1D patients. T1D is associated with both hyperketonemia (acetoacetate and β-hydroxybutyrate) and hyperglycemia. This study also examined the role of hyperglycemia and hyperketonemia per se in decreased CSE activity using U937 monocytes and PBMC isolated from healthy subjects. Livers from streptozotocin-treated T1D rats demonstrated a significantly higher reactive oxygen species production, lower CSE protein...
Source: Journal of Biological Chemistry - April 25, 2014 Category: Chemistry Authors: Manna, P., Gungor, N., McVie, R., Jain, S. K. Tags: Metabolism Source Type: research
Down-regulation of Vascular BK-{beta}1 Expression by MuRF1 Protein Synthesis and Degradation
In this study, we hypothesized that MuRF1 participated in BK-β1 proteolysis, leading to the down-regulation of BK channel activation and impaired coronary function in diabetes. Combining patch clamp and molecular biological approaches, we found that MuRF1 expression was enhanced, accompanied by reduced BK-β1 expression, in high glucose-cultured human coronary SMCs and in diabetic vessels. Knockdown of MuRF1 by siRNA in cultured human SMCs attenuated BK-β1 ubiquitination and increased BK-β1 expression, whereas adenoviral expression of MuRF1 in mouse coronary arteries reduced BK-β1 expression and diminished BK channel-m...
Source: Journal of Biological Chemistry - April 11, 2014 Category: Chemistry Authors: Yi, F., Wang, H., Chai, Q., Wang, X., Shen, W.-K., Willis, M. S., Lee, H.-C., Lu, T. Tags: Molecular Bases of Disease Source Type: research
PPAR{gamma} Regulation by HAUSP Molecular Bases of Disease
In this study, herpesvirus-associated ubiquitin-specific protease (HAUSP) was isolated as a binding partner of PPARγ. Both endogenous and exogenous PPARγ associated with HAUSP in co-immunoprecipitation analysis. HAUSP, but not the catalytically inactive HAUSP C223S mutant, increased the stability of both endogenous and exogenous PPARγ through its deubiquitinating activity. Site-directed mutagenesis experiments showed that the Lys462 residue of PPARγ is critical for ubiquitination. HBX 41,108, a specific inhibitor of HAUSP, abolished the increase in PPARγ stability induced by HAUSP. In addition, knockdown of endogenous...
Source: Journal of Biological Chemistry - November 15, 2013 Category: Chemistry Authors: Lee, K. W., Cho, J. G., Kim, C. M., Kang, A. Y., Kim, M., Ahn, B. Y., Chung, S. S., Lim, K.-H., Baek, K.-H., Sung, J.-H., Park, K. S., Park, S. G. Tags: Metabolism Source Type: research
CTSB Contributes to Atg7-induced Proinflammatory Response Metabolism
Impairment of glucose-stimulated insulin secretion caused by the lipotoxicity of palmitate was found in β-cells. Recent studies have indicated that defects in autophagy contribute to pathogenesis in type 2 diabetes. Here, we report that autophagy-related 7 (Atg7) induced excessive autophagic activation in INS-1(823/13) cells exposed to saturated fatty acids. Atg7-induced cathepsin B (CTSB) overexpression resulted in an unexpected significant increase in proinflammatory chemokine and cytokine production levels of IL-1β, monocyte chemotactic protein-1, IL-6, and TNF-α. Inhibition of receptor-interacting protein did not af...
Source: Journal of Biological Chemistry - October 18, 2013 Category: Chemistry Authors: Li, S., Du, L., Zhang, L., Hu, Y., Xia, W., Wu, J., Zhu, J., Chen, L., Zhu, F., Li, C., Yang, S. Tags: Cell Biology Source Type: research
Activated Legumain in Alzheimer Disease Neurobiology
Neurofibrillary pathology of abnormally hyperphosphorylated Tau is a key lesion of Alzheimer disease and other tauopathies, and its density in the brain directly correlates with dementia. The phosphorylation of Tau is regulated by protein phosphatase 2A, which in turn is regulated by inhibitor 2, I2PP2A. In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2PP2A is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I2NTF) and the C-terminal fragment (I2CTF). Both I2NTF and I2CTF are known to bind to the catalytic subun...
Source: Journal of Biological Chemistry - June 14, 2013 Category: Chemistry Authors: Basurto-Islas, G., Grundke-Iqbal, I., Tung, Y. C., Liu, F., Iqbal, K. Tags: Molecular Bases of Disease Source Type: research
TR{alpha} Induces Reprogramming of Pancreatic Acinar Cells Gene Regulation
One goal of diabetic regenerative medicine is to instructively convert mature pancreatic exocrine cells into insulin-producing cells. We recently reported that ligand-bound thyroid hormone receptor α (TRα) plays a critical role in expansion of the β-cell mass during postnatal development. Here, we used an adenovirus vector that expresses TRα driven by the amylase 2 promoter (AdAmy2TRα) to induce the reprogramming of pancreatic acinar cells into insulin-producing cells. Treatment with l-3,5,3-triiodothyronine increases the association of TRα with the p85α subunit of phosphatidylinositol 3-kinase (PI3K), leading to th...
Source: Journal of Biological Chemistry - May 31, 2013 Category: Chemistry Authors: Furuya, F., Shimura, H., Asami, K., Ichijo, S., Takahashi, K., Kaneshige, M., Oikawa, Y., Aida, K., Endo, T., Kobayashi, T. Tags: Cell Biology Source Type: research
