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aso-antisense-oligonucleotide

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Meeting Abstracts
Journal: Diabetes
Diabetes 2020;69(Supplement_1):1051-P
Published: 01 June 2020
... endpoint was the percent change in serum triglycerides from baseline to week 27. All other endpoints were also analyzed at week 27. Treatment resulted in a 60±26 (mean±SD) % reduction in triglycerides from a baseline of 818±432 mg/dL. Consistent with antisense reduction of ANGPTL3 mRNA, circulating ANGPTL3...
Meeting Abstracts
Journal: Diabetes
Diabetes 2018;67(Supplement_1):2439-PUB
Published: 01 July 2018
... fed a high fat, fructose, and cholesterol (AMLN) diet for 24 weeks and found elevated mRNA expression of Taz in the livers compared to the lean mice. We treated C57B/6 mice fed the AMLN diet for 24 weeks with ASOs targeting Taz RNA. After 12 weeks of Taz ASO treatment, we observed a 95% knockdown...
Meeting Abstracts
Journal: Diabetes
Diabetes 2018;67(Supplement_1):149-OR
Published: 01 July 2018
... metabolism of fructose (50% of dietary sucrose) and improve numerous facets of metabolism. ASO’s potently decrease target expression in liver and WAT and we hypothesized that a novel KHK ASO would prevent NAFLD and insulin resistance in normal rats fed a low fat (12% calories from fat), sucrose containing...
Images
Effect of iNOS <span class="search-highlight">antisense</span> <span class="search-highlight">oligonucleotide</span> (<span class="search-highlight">ASO</span>) on iNOS expression, S-nitros...
Published: 01 April 2005
FIG. 4. Effect of iNOS antisense oligonucleotide (ASO) on iNOS expression, S-nitrosation of IRβ/IRS-1/Akt, and insulin signaling in muscle of ob/ob diabetic mice. A: iNOS protein level in ob/ob diabetic mice compared with iNOS ASO-treated ob/ob mice. B: Insulin sensitivity evaluated by glucose disappearance rates, measured by the 30-min insulin tolerance test. S-nitrosation of IRβ (C), IRS-1 (D), and Akt (E) is shown, determined by the biotin switch method. Insulin-stimulated tyrosine phosphorylation of IRβ (F) and IRS-1 (G), IRS-1 protein levels (H), and insulin-stimulated serine phosphorylation of Akt (I) is indicated. *P < 0.05, ob/ob vs. lean and ob/ob ASO. Bars represent means ± SE from six to eight mice. IB, immunoblotting; IP, immunoprecipitated. FIG. 4. Effect of iNOS antisense oligonucleotide (ASO) on iNOS expression, S-nitrosation of IRβ/IRS-1/Akt, and insulin signaling in muscle of ob/ob diabetic mice. A: iNOS protein level in ob/ob diabetic mice compared with iNOS ASO-treated ob/ob mice. B: Insulin sensitivity evaluated by glucose disappearance rates, measured by the 30-min insulin tolerance test. S-nitrosation of IRβ (C), IRS-1 (D), and Akt (E) is shown, determined by the biotin switch method. Insulin-stimulated tyrosine phosphorylation of IRβ (F) and IRS-1 (G), IRS-1 protein levels (H), and insulin-stimulated serine phosphorylation of Akt (I) is indicated. *P < 0.05, ob/ob vs. lean and ob/ob ASO. Bars represent means ± SE from six to eight mice. IB, immunoblotting; IP, immunoprecipitated. More
Journal Articles
Journal: Diabetes
Diabetes 2004;53(2):410–417
Published: 01 February 2004
... the consequences of hyperglucagonemia and improve blood glucose control in diabetic patients. This study describes the antidiabetic effects of a specific glucagon receptor antisense oligonucleotide (GR-ASO) in db/db mice. The ability of GR-ASOs to inhibit glucagon receptor mRNA expression was demonstrated...
Journal Articles
Journal: Diabetes
Diabetes 2003;52(1):21–28
Published: 01 January 2003
... and a drug target for treatment of type 2 diabetes. Using PTP1B antisense oligonucleotides (ASOs), effects of decreased PTP1B levels on insulin signaling in diabetic ob/ob mice were examined. Insulin stimulation, prior to sacrifice, resulted in no significant activation of insulin signaling pathways...
Journal Articles
Journal: Diabetes
Diabetes 2006;55(7):2042–2050
Published: 01 July 2006
... gluconeogenesis. The transcription factor Foxo1 links insulin signaling to decreased transcription of PEPCK and glucose-6-phosphatase (G6Pase) and provides a possible therapeutic target in insulin-resistant states. Synthetic, optimized antisense oligonucleotides (ASOs) specifically inhibit Foxo1 expression. Here...
Journal Articles
Journal: Diabetes
Diabetes 2005;54(6):1846–1853
Published: 01 June 2005
... used optimized antisense oligonucleotides (ASOs) to cause selective reduction of the glucocorticoid receptor (GCCR) in liver and white adipose tissue (WAT) and evaluated the resultant changes in glucose and lipid metabolism in several rodent models of diabetes. Treatment of ob/ob mice...
Journal Articles
Journal: Diabetes
Diabetes 2002;51(4):1028–1034
Published: 01 April 2002
... an antisense oligonucleotide (ASO) strategy in an effort to specifically inhibit the expression of PTEN. Transfection of cells in culture with ASO targeting PTEN reduced PTEN mRNA and protein levels and increased insulin-stimulated Akt phosphorylation in α-mouse liver-12 (AML12) cells. Systemic administration...
Includes: Supplementary data
Meeting Abstracts
Journal: Diabetes
Diabetes 2020;69(Supplement_1):2066-P
Published: 01 June 2020
... therapeutically viable due to their ability to increase proliferation in peripheral tissues. Previously we demonstrated that generation 2.5 antisense oligonucleotides (ASO) conjugated to a glucagon like peptide 1 receptor (GLP-1R) agonist can specifically target the pancreatic beta cell. When compared to control...
Meeting Abstracts
Journal: Diabetes
Diabetes 2019;68(Supplement_1):2143-P
Published: 01 June 2019
... is widely regarded as a key contributor to T2D disease progression. Antisense oligonucleotides (ASOs) have been shown to provide substantial therapeutic benefit for numerous unmet medical needs. However, unconjugated ASOs have shown minimal activity in pancreatic beta cells, limiting their use...
Journal Articles
Journal: Diabetes
Diabetes 2015;64(5):1603–1614
Published: 18 December 2014
... cause insulin resistance, and the lowering of RBP4 levels improves glucose homeostasis. Since lowering TTR levels increases renal clearance of RBP4, we determined whether decreasing TTR levels with antisense oligonucleotides (ASOs) improves glucose metabolism and insulin sensitivity in obesity. TTR-ASO...
Meeting Abstracts
Journal: Diabetes
Diabetes 2020;69(Supplement_1):1844-P
Published: 01 June 2020
... lysophospholipids. Foxo1 is an insulin responsive transcription factor. To biologically validate the role of Agpat5 in obesity associated hyperinsulinemia, we treated obese high fat fed mice with an antisense oligonucleotide (ASO) that targets Agpat5 to inhibit its gene expression. We show that Agpat5 ASO treated...
Journal Articles
Journal: Diabetes
Diabetes 2013;62(7):2183–2194
Published: 14 June 2013
... the role of pyruvate carboxylase in regulating glucose and lipid metabolism in rats through a loss-of-function approach using a specific antisense oligonucleotide (ASO) to decrease expression predominantly in liver and adipose tissue. Pyruvate carboxylase ASO reduced plasma glucose concentrations...
Includes: Supplementary data
Journal Articles
Journal: Diabetes
Diabetes 2019;68(3):527–542
Published: 14 December 2018
...Sebastian Brachs; James Polack; Maria Brachs; Kerstin Jahn-Hofmann; Ralf Elvert; Anja Pfenninger; Felix Bärenz; Daniel Margerie; Knut Mai; Joachim Spranger; Aimo Kannt Antisense oligonucleotide knockdown (ASO-KD) of nicotinamide N-methyltransferase (NNMT) in high-fat diet (HFD)–fed mice...
Includes: Supplementary data
Meeting Abstracts
Journal: Diabetes
Diabetes 2018;67(Supplement_1):243-LB
Published: 01 July 2018
... to inhibit IRK activation and cause insulin resistance. However, the importance of DAG in lipid-induced hepatic insulin resistance remains controversial. To test the physiological effect of acute DAG accumulation on hepatic insulin sensitivity, we used antisense oligonucleotide (ASO) to specifically inhibit...
Meeting Abstracts
Journal: Diabetes
Diabetes 2018;67(Supplement_1):2030-P
Published: 01 July 2018
... organs. Recent research suggests the involvement of NNMT in the pathogenesis of obesity, insulin resistance and related metabolic disease. Antisense oligonucleotide (ASO) knockdown in high-fat diet (HFD)-fed mice led to reduced weight gain, relative fat mass, plasma insulin levels and improved glucose...
Journal Articles
Journal: Diabetes
Diabetes 2002;51(8):2405–2411
Published: 01 August 2002
... of PTP1B antisense (ISIS-113715) treatment on insulin resistance and the regulation of insulin signaling in ob/ob diabetic mice. Interestingly, hyperglycemic ob/ob mice as well as db/db mice treated with the PTP1B antisense oligonucleotide (ASO...
Journal Articles
Journal: Diabetes
Diabetes 2014;63(7):2284–2296
Published: 14 June 2014
... resistance is unknown. We show that the expression of Mogat1, which encodes MGAT1, and MGAT activity are also increased in diet-induced obese (DIO) and ob/obmice. To probe the metabolic effects of MGAT1 in the livers of obese mice, we administered antisense oligonucleotides (ASOs) against...
Includes: Supplementary data
Journal Articles
Journal: Diabetes
Diabetes 2013;62(1):137–148
Published: 13 December 2012
..., metabolic characteristics, signaling proteins, and neuropeptide expression were measured in response to fasting and refeeding, intracerebroventricular insulin and leptin, and Tub antisense oligonucleotide (ASO). Tub tyrosine phosphorylation (Tub-p-tyr) is modulated by nutritional status. Tub...
Includes: Supplementary data