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Condition: Diabetes Type 2

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Total 421 results found since Jan 2013.

The impact of sitagliptin in palmitic acid-induced insulin resistance in human HepG2 cells through the suppressor of cytokine signaling 3/phosphoinositide 3-kinase/protein kinase B pathway
In this study, we established an in vitro insulin resistance cell model for human HepG2 cells to investigate the possible mechanism of the effect of sitagliptin on glucose metabolism via the SOCS3/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. Since insulin resistance first develops in the liver, palmitic acid was used to generate an insulin resistance cell model in human HepG2 cells, after which small interfering ribonucleic acid (siRNA)-SOCS3 and sitagliptin were used to intervene. We then examined the changes in cell viability and biochemical indices in the insulin resistance cell model. SOCS3, Akt, an...
Source: Journal of Physiology and Pharmacology - July 15, 2023 Category: Drugs & Pharmacology Authors: R Ma L Quan Q-Q-G Aleteng L Li J Zhu S Jiang Source Type: research

AMP-Activated Protein Kinase as Regulator of P2Y6 Receptor-Induced Insulin Secretion in Mouse Pancreatic β-Cells.
Abstract 5'-AMP-activated protein kinase (AMPK) and its pharmacological modulators have been targeted for treating type 2 diabetes. Extracellular uridine 5'-diphosphate (UDP) activates P2Y(6) receptors (P2Y(6)Rs) in pancreatic β-cells to release insulin and reduce apoptosis, which would benefit diabetes. Here, we studied the role of P2Y(6)R in activation of AMPK in MIN6 mouse pancreatic β-cells and insulin secretion. Treatment with a potent P2Y(6)R dinucleotide agonist MRS2957 (500nM) activated AMPK, which was blocked by P2Y(6)R-selective antagonist MRS2578. Also, MRS2957 induced phosphorylation of acetyl-coenzy...
Source: Biochemical Pharmacology - January 17, 2013 Category: Drugs & Pharmacology Authors: Balasubramanian R, Maruoka H, Jayasekara MP, Gao ZG, Jacobson KA Tags: Biochem Pharmacol Source Type: research

Inhibitory Cross‐talk between the AMPK and ERK pathways mediates endoplasmic reticulum stress‐induced insulin resistance in skeletal muscle
Conclusions And ImplicationsInhibition of ERK signaling pathways by a chemical inhibitor and knockdown of ERK improved AMPK and Akt signalings and reversed ER stress‐induced insulin resistance in L6 myotubes. These findings suggest that ERK signaling plays an important role in the regulation of insulin signals in muscle cells under ER stress.
Source: British Journal of Pharmacology - February 4, 2013 Category: Drugs & Pharmacology Authors: Seung‐Lark Hwang, Yong‐Tae Jeong, Xian Li, Yong Deuk Kim, Lu Yue, Young‐Chae Chang, In‐Kyu Lee, Hyeun Wook Chang Tags: Research Paper Source Type: research

Manganese, ICAM-1, MCP-1, and Endothelial Cell Dysfunction Molecular Bases of Disease
This study examines the hypothesis that Mn2+ supplementation can reduce the markers/risk factors of endothelial dysfunction in type 2 diabetes. Human umbilical vein endothelial cells (HUVECs) were cultured with or without Mn2+ supplementation and then exposed to high glucose (HG, 25 mm) to mimic diabetic conditions. Mn2+ supplementation caused a reduction in monocyte adhesion to HUVECs treated with HG or MCP-1. Mn2+ also inhibited ROS levels, MCP-1 secretion, and ICAM-1 up-regulation in HUVECs treated with HG. Silencing studies using siRNA against MnSOD showed that similar results were observed in MnSOD knockdown HUVECs fo...
Source: Journal of Biological Chemistry - March 1, 2013 Category: Chemistry Authors: Burlet, E., Jain, S. K. Tags: Metabolism Source Type: research

Small molecule kaempferol modulates PDX-1 protein expression and subsequently promotes pancreatic β-cell survival and function via CREB
Abstract: Chronic hyperlipidemia causes β-cell apoptosis and dysfunction, thereby contributing to the pathogenesis of type 2 diabetes (T2D). Thus, searching for agents to promote pancreatic β-cell survival and improve its function could be a promising strategy to prevent and treat T2D. We investigated the effects of kaempferol, a small molecule isolated from ginkgo biloba, on apoptosis and function of β-cells and further determined the mechanism underlying its actions. Kaempferol treatment promoted viability, inhibited apoptosis and reduced caspase-3 activity in INS-1E cells and human islets chronically exposed to palmi...
Source: The Journal of Nutritional Biochemistry - July 23, 2012 Category: Biochemistry Authors: Yanling Zhang, Wei Zhen, Pierre Maechler, Dongmin Liu Tags: Research Articles Source Type: research

Delivery of siRNA to adipose macrophages in mice Physiology
Adipose tissue (AT) inflammation and infiltration by macrophages is associated with insulin resistance and type 2 diabetes in obese humans, offering a potential target for therapeutics. However, whether AT macrophages (ATMs) directly contribute to systemic glucose intolerance has not been determined. The reason is the lack of methods to ablate...
Source: Proceedings of the National Academy of Sciences - May 14, 2013 Category: Science Authors: Aouadi, M., Tencerova, M., Vangala, P., Yawe, J. C., Nicoloro, S. M., Amano, S. U., Cohen, J. L., Czech, M. P. Tags: Biological Sciences Source Type: research

Metformin Enhances Cisplatin Cytotoxicity by Suppressing Stat3 Activity Independently of the LKB1-AMPK Pathway.
This study demonstrated a correlation between Stat3 phosphorylation and cisplatin cytotoxicity using AS2 (PC14PE6/AS2)-derived cell lines (AS2/S3C) that contained constitutively active Stat3 plasmids as a model. A Stat3 inhibitor (JSI-124) enhanced the cisplatin sensitivity in AS2 cells, whereas metformin inhibited Stat3 phosphorylation and enhanced cisplatin cytotoxicity. By contrast, another AMPK activator (AICAR) failed to produce these effects. LKB1-AMPK silencing by siRNA or mTOR inhibition by rapamycin or pp242 did not alter the effect of metformin on Stat3 activity suppression, suggesting that metformin can modulate...
Source: American Journal of Respiratory Cell and Molecular Biology - March 22, 2013 Category: Molecular Biology Authors: Lin CC, Yeh HH, Huang WL, Yan JJ, Lai WW, Su WP, Chen HH, Su WC Tags: Am J Respir Cell Mol Biol Source Type: research

Activation of type 2 cannabinoid receptors (CB2R) promotes fatty acid oxidation through the SIRT1/PGC-1α pathway.
In this study, we report that a specific agonist of the type 2 cannabinoid receptor (CB2R) can lead to fatty acid oxidation through the PGC-1α pathway. We have found that CB2R is expressed in differentiated C2C12 myotubes, and that use of the specific agonist trans-caryophyllene (TC) stimulates sirtuin 1 (SIRT1) deacetylase activity by increasing the phosphorylation of cAMP response element-binding protein (CREB), thus leading to increased levels of PGC-1α deacetylation. This use of TC treatment increases the expression of genes linked to the fatty acid oxidation pathway in a SIRT1/PGC-1α-dependent mechanism and also dr...
Source: Biochemical and Biophysical Research communications - June 4, 2013 Category: Biochemistry Authors: Zheng X, Sun T, Wang X Tags: Biochem Biophys Res Commun Source Type: research

Pinusolide improves high glucose-induced insulin resistance via activation of AMP-activated protein kinase.
In this study, we found that pinusolide stimulated AMPK phosphorylation and glucose uptake and these effects were significantly reduced by siRNA LKB1 or compound C, suggesting that enhanced glucose uptake by pinusolide is predominantly accomplished via an LKB1-mediated AMPK activation pathway. An insulin resistance state was induced by exposing cells to 30 mM glucose, as indicated by reduced insulin-stimulated tyrosine phosphorylation of IRS-1 and glucose uptake. Under these conditions, the phosphorylation of AMPK and ACC were decreased. Surprisingly, disrupted insulin signaling and decreased AMPK activity by high glucose ...
Source: Biochemical and Biophysical Research communications - July 2, 2013 Category: Biochemistry Authors: Hwang SL, Jeong YT, Yang JH, Li X, Lu Y, Son JK, Chang HW Tags: Biochem Biophys Res Commun Source Type: research

In vivo Activating Transcription factor 3 silencing ameliorates the AMPK compensatory effects for ER stress-mediated β-cell dysfunction during the progression of type-2 diabetes.
Abstract In obese Zucker diabetic fatty (ZDF) rats, ER stress is associated with insulin resistance and pancreatic β-cell dysfunction; however the exact mechanisms by which ER stress drives type-2 diabetes remain uncertain. Here, we investigated the role of ATF3 on the preventive regulation of AMPK against ER stress-mediated β-cell dysfunction during the end-stage progression of hyperglycemia in ZDF rats. The impaired glucose metabolism and β-cell dysfunction were significantly increased in late-diabetic phase 19-week-old ZDF rats. Although AMPK phosphorylation reduced in 6- and 12-week-old ZDF rats was remarka...
Source: Cellular Signalling - August 2, 2013 Category: Cytology Authors: Kim JY, Park KJ, Kim GH, Jeong EA, Lee DY, Lee SS, Kim DJ, Roh GS, Song J, Ki SH, Kim WH Tags: Cell Signal Source Type: research

Caveolin-1 upregulation in diabetic fibroblasts and wounded tissues: implication for understanding the underlying mechanisms of non-healing diabetic ulcers.
Abstract A heightened state of oxidative stress and senescence of fibroblasts constitute potential therapeutic targets in non-healing diabetic wounds. Here, we studied the underlying mechanism mediating diabetes-induced cellular senescence using in vitro cultured dermal fibroblasts and in vivo circular wounds. Our results demonstrated that the total antioxidant capacity, mRNA levels of thioredoxinreductase and glucose-6-phosphate dehydrogenase as well as the ratio of NADPH/NADP were markedly decreased in fibroblasts from patients with type 2 diabetes (DFs). Consistent with this shifts in favor of excessive reactiv...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 13, 2013 Category: Physiology Authors: Bitar MS, Abdel-Halim SM, Al-Mulla F Tags: Am J Physiol Endocrinol Metab Source Type: research

Gestational diabetes impairs Nrf2-mediated adaptive antioxidant defenses and redox signaling in fetal endothelial cells in utero.
We examined the effects of GDM on the proteome, redox status and nuclear factor erythroid 2-related factor 2 (Nrf2) mediated antioxidant gene expression in human fetal endothelial cells. Proteomic analysis revealed that proteins involved in redox homeostasis were significantly altered in GDM and associated with increased mitochondrial superoxide generation, protein oxidation, DNA damage and diminished glutathione synthesis. In GDM cells, the lipid peroxidation product 4-hydroxynonenal (HNE) failed to induce nuclear Nrf2 accumulation and mRNA and/or protein expression of Nrf2 and its target genes NAD(P)H:quinone oxidoreduct...
Source: Diabetes - August 23, 2013 Category: Endocrinology Authors: Cheng X, Chapple SJ, Patel B, Puszyk W, Sudgen D, Yin X, Mayr M, Siow RC, Mann GE Tags: Diabetes Source Type: research

Caveolin-1/PTRF upregulation constitutes a mechanism for mediating p53-induced cellular senescence: implications for evidence-based therapy of delayed wound healing in diabetes
A heightened state of oxidative stress and senescence of fibroblasts constitute potential therapeutic targets in nonhealing diabetic wounds. Here, we studied the underlying mechanism mediating diabetes-induced cellular senescence using in vitro cultured dermal fibroblasts and in vivo circular wounds. Our results demonstrated that the total antioxidant capacity and mRNA levels of thioredoxinreductase and glucose-6-phosphate dehydrogenase as well as the ratio of NADPH/NADP were decreased markedly in fibroblasts from patients with type 2 diabetes (DFs). Consistent with this shift in favor of excessive reactive oxygen species,...
Source: AJP: Endocrinology and Metabolism - October 15, 2013 Category: Endocrinology Authors: Bitar, M. S., Abdel-Halim, S. M., Al-Mulla, F. Tags: Articles 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