Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle

2001 ◽  
Vol 7 (10) ◽  
pp. 1138-1143 ◽  
Author(s):  
Mylène Perreault ◽  
André Marette
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Targeted Disruption ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Targeted Disruption of Inducible Nitric Oxide Synthase Protects Against Aging, S-Nitrosation, and Insulin Resistance in Muscle of Male Mice

Diabetes ◽  
2012 ◽  
Vol 62 (2) ◽  
pp. 466-470 ◽  
Author(s):  
E. R. Ropelle ◽  
J. R. Pauli ◽  
D. E. Cintra ◽  
A. S. da Silva ◽  
C. T. De Souza ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Male Mice ◽  
Targeted Disruption ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Inducible Nitric Oxide Synthase Deficiency in Myeloid Cells Does Not Prevent Diet-Induced Insulin Resistance

2010 ◽  
Vol 24 (7) ◽  
pp. 1413-1422 ◽  
Author(s):  
Min Lu ◽  
PingPing Li ◽  
Jan Pferdekamper ◽  
WuQiang Fan ◽  
Maziyar Saberi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Myeloid Cells ◽  
Mixed Effect ◽  
Insulin Resistant ◽  
Oxide Synthase ◽  
Inos Inhibition ◽  
Inducible Nitric Oxide

Abstract Recent findings denote an important contribution of macrophage inflammatory pathways in causing obesity-related insulin resistance. Inducible nitric oxide synthase (iNOS) is activated in proinflammatory macrophages and modestly elevated in insulin-responsive tissues. Although the benefits of systemic iNOS inhibition in insulin-resistant models have been demonstrated, the role of macrophage iNOS in metabolic disorders is not clear. In the current work, we used bone marrow transplantation (BMT) to generate mice with myeloid iNOS deficiency [iNOS BMT knockout (KO)]. Interestingly, disruption of iNOS in myeloid cells did not protect mice from high-fat diet-induced obesity and insulin resistance. When mice were treated with the iNOS inhibitor, N6-(1-Iminoethyl)-L-lysine hydrochloride (L-NIL), we observed a significant and comparable improvement of glucose homeostasis and insulin sensitivity in both wild-type and iNOS BMT KO mice. We further demonstrated that absence of iNOS in primary macrophages did not affect acute TLR4 signaling pathways and had only a modest and mixed effect on inflammatory gene expression. With respect to TNFα treatment, iNOS KO macrophages showed, if anything, a greater inflammatory response. In summary, we conclude that iNOS inhibition in tissues other than myeloid cells is responsible for the beneficial effects in obesity/insulin resistance.

Inducible nitric oxide synthase plays a role in LPS-induced hyperglycemia and insulin resistance

2002 ◽  
Vol 282 (2) ◽  
pp. E386-E394 ◽  
Author(s):  
Hiroki Sugita ◽  
Masao Kaneki ◽  
Eriko Tokunaga ◽  
Michiko Sugita ◽  
Chieko Koike ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Glycogen Phosphorylase ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The molecular mechanisms underlying endotoxin-induced insulin resistance remain unclear. Endotoxin or lipopolysaccharide (LPS) injection is a potent stimulator of inducible nitric oxide synthase (iNOS). This study in rats, using the specific iNOS inhibitor aminoguanidine, investigated the role of iNOS in endotoxin-induced hyperglycemia and insulin resistance. LPS injection led to hyperglycemia, insulin resistance, and increased iNOS protein expression and activity. Aminoguanidine prevented LPS-induced hyperglycemia without affecting insulin levels or iNOS expression. Aminoguanidine attenuated the LPS-induced insulin resistance, reflected by the requirement for a higher glucose infusion rate to maintain euglycemia during a hyperinsulinemic clamp study. Aminoguanidine completely blocked the LPS-elevated hepatic glucose output and also inhibited LPS-induced increases in hepatic glycogen phosphorylase activities and phospho enolpyruvate carboxykinase (PEPCK) mRNA expression, key enzymes for glycogenolysis and gluconeogenesis, respectively. Thus, these data demonstrate an important role for iNOS in LPS-induced insulin resistance, evidenced by the attenuation of LPS-induced hyperglycemia and reversal of increased hepatic glucose output by aminoguanidine. The protective effect of aminoguanidine on insulin resistance is probably by attenuation of hepatic glucose output via its inhibition of key enzymes for glycogenolysis and gluconeogenesis, including glycogen phosphorylase and PEPCK.

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