Cited by 209Adipokines, Inflammation, and Metabolic DiseasesNitric Oxide and Endothelin EffectsPancreatic function and diabetes

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A Role for iNOS in Fasting Hyperglycemia and Impaired Insulin Signaling in the Liver of Obese Diabetic Mice

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Fujimoto, Masaki, Shimizu, Nobuyuki, Kunii, Kaiko, Martyn, J.A. Jeevendra, Ueki, Kohjiro, Kaneki, Masao·2005·Diabetes

DOI 10.2337/diabetes.54.5.1340

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Abstract

Chronic inflammation has been postulated to play an important role in the pathogenesis of insulin resistance. Inducible nitric oxide synthase (iNOS) has been implicated in many human diseases associated with inflammation. iNOS deficiency was shown to prevent high-fat diet-induced insulin resistance in skeletal muscle but not in the liver. A role for iNOS in fasting hyperglycemia and hepatic insulin resistance, however, remains to be investigated in obesity-related diabetes. To address this issue, we examined the effects of a specific inhibitor for iNOS, L-NIL, in obese diabetic (ob/ob) mice. iNOS expression was increased in the liver of ob/ob mice compared with wild-type mice. Treatment with iNOS inhibitor reversed fasting hyperglycemia with concomitant amelioration of hyperinsulinemia and improved insulin sensitivity in ob/ob mice. iNOS inhibitor also increased the protein expression of insulin receptor substrate (IRS)-1 and -2 1.5- and 2-fold, respectively, and enhanced IRS-1- and IRS-2-mediated insulin signaling in the liver of ob/ob mice. Exposure to NO donor and ectopically expressed iNOS decreased the protein expression of IRS-1 and -2 in cultured hepatocytes. These results suggest that iNOS plays a role in fasting hyperglycemia and contributes to hepatic insulin resistance in ob/ob mice.

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Aspirin attenuates insulin resistance in muscle of diet-induced obese rats by inhibiting inducible nitric oxide synthase production and S-nitrosylation of IRβ/IRS-1 and Akt
Carvalho-Filho, M. A., Ropelle, E. R., Pauli, R. J., Cintra, D. E., Tsukumo, D. M. L., Silveira, L. R., Curi, R., Carvalheira, J. B. C., Velloso, L. A., & Saad, M. J. A. (2009) · Diabetologia · doi:10.1007/s00125-009-1498-1 · Cited by 63
“In more prolonged high-fat diet treatment these effects of iNOS on hepatic insulin resistance would probably be more evident [28].”
Coagulation and Endothelial Dysfunction Associated with NAFLD: Current Status and Therapeutic Implications
Ogresta, D., Mrzljak, A., Berković, M. C., Bilić-Čurčić, I., Stojsavljević, S., & Virović-Jukić, L. (2022) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2021.00268 · Cited by 58
Inhibition of adipocyte inflammation and macrophage chemotaxis by butein
Wang, Z., Lee, Y., Eun, J. S., & Bae, E. J. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.05.031 · Cited by 59
Protective Effect of Proanthocyanidin against Diabetic Oxidative Stress
Yokozawa, T., Cho, E. J., Park, C. H., & Kim, J. H. (2011) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2012/623879 · Cited by 56
“COX-2 and iNOS expressions were up-regulated under insulin resistance, obesity, hyperglycemia, and oxidative stress [48].”
Background
DPP-4 Inhibitors as Potential Candidates for Antihypertensive Therapy: Improving Vascular Inflammation and Assisting the Action of Traditional Antihypertensive Drugs
Zhang, J., Chen, Q., Zhong, J., Liu, C., Zheng, B., & Gong, Q. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01050 · Cited by 57
Phenolics and anthocyanins in berries of European cranberry and their antimicrobial activity
Česonienė, L., Jasutienė, I., & Šarkinas, A. (2024) · PubMed · doi:10.5281/zenodo.11174808 · Cited by 56
Pentoxifylline reduces the inflammatory process in diabetic rats: relationship with decreases of pro-inflammatory cytokines and inducible nitric oxide synthase
Garcia, F. A. D. O., Rebouças, J. F., Balbino, T. Q., da Silva, T. G., de Carvalho-Júnior, C. H. R., Cerqueira, G. S., Brito, G. A. D. C., & Viana, G. S. D. B. (2015) · Journal of Inflammation · doi:10.1186/s12950-015-0080-5 · Cited by 57
“Earlier results [57] suggest that iNOS plays a role in hyperglycemia and contributes to hepatic insulin resistance in ob/ob mice.”
Result
Sea cucumber peptides exert anti-inflammatory activity through suppressing NF-κB and MAPK and inducing HO-1 in RAW264.7 macrophages
Song, J., Li, T., Cheng, X., Ji, X., Gao, D., Du, ‬., Jiang, N., Liu, X., & Mao, X. (2016) · Food & Function · doi:10.1039/c5fo01622c · Cited by 53
Nitric oxide mediates the insulin sensitizing effects of β-sitosterol in high fat diet-fed rats
Radika, M. K., Viswanathan, P., & Anuradha, C. V. (2013) · Nitric Oxide · doi:10.1016/j.niox.2013.04.007 · Cited by 52
The impact of dietary fructose on gut permeability, microbiota, abdominal adiposity, insulin signaling and reproductive function
Güney, C., Bal, N. B., & Akar, F. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e18896 · Cited by 53
“Inflammatory factors, especially iNOS, may have a role in the coupling of metabolic and vascular insulin resistance as well as impaired insulin signaling in the liver from diabetic obese mice [182,183].”
Background
Deletion of Inducible Nitric-Oxide Synthase in Leptin-Deficient Mice Improves Brown Adipose Tissue Function
Becerril, S., Rodrı́guez, A., Catalán, V., Sáinź, N., Ramírez, B., Collantes, M., Peñuelas, I., Gómez‐Ambrosi, J., & Frühbeck, G. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010962 · Cited by 50
“In this line, the present study shows that ablation of the iNOS gene in ob/ob mice improves the impaired carbohydrate metabolism, as previously described [69,70], decreasing glycemia and insulinemia as well as increasing adiponectinemia, at the same time as it ameliorates lipid homeostasis through a decrease in serum…”
Result
Intrahepatic vascular changes in non-alcoholic fatty liver disease: Potential role of insulin-resistance and endothelial dysfunction
Pasarín, M., Abraldeṣ, J. G., Liguori, E., Kok, B., & Mura, V. L. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i37.6777 · Cited by 52
Translational Implications of the Alcohol-Metabolizing Enzymes, Including Cytochrome P450-2E1, in Alcoholic and Nonalcoholic Liver Disease
Song, B., Akbar, M. D., Jo, I., Hardwick, J. P., & Abdelmegeed, M. A. (2015) · Advances in pharmacology · doi:10.1016/bs.apha.2015.04.002 · Cited by 51
Treatment with a Catalytic Superoxide Dismutase (SOD) Mimetic Improves Liver Steatosis, Insulin Sensitivity, and Inflammation in Obesity-Induced Type 2 Diabetes
Coudriet, G. M., Delmastro-Greenwood, M. M., Previte, D. M., Marré, M. L., O’Connor, E., Novak, E. M., Vincent, G., Mollen, K. P., Lee, S., Dong, H. H., et al. (2017) · Antioxidants · doi:10.3390/antiox6040085 · Cited by 50
“Previous studies have shown that NF-κB-dependent inducible nitric oxide synthase (iNOS) plays an important role in insulin resistance [58] and that liver-specific inhibition of iNOS reverses obesity-induced insulin resistance [59,60].”
Targeted disruption of the iNOS gene improves adipose tissue inflammation and fibrosis in leptin-deficient ob/ob mice: role of tenascin C
Becerril, S., Rodríguez, A., Catalán, V., Méndez-Giménez, L., Ramírez, B., Sáinź, N., Llorente, M., Unamuno, X., Gómez‐Ambrosi, J., & Frühbeck, G. (2018) · International Journal of Obesity · doi:10.1038/s41366-018-0005-5 · Cited by 48
Induction of cytochrome promotes liver injury in ob/ob mice
Dey, A., & Cederbaum, A. I. (2007) · Hepatology · doi:10.1002/hep.21603 · Cited by 46
Prevention of free fatty acid-induced lipid accumulation, oxidative stress, and cell death in primary hepatocyte cultures by a Gynostemma pentaphyllum extract
Müller, C., Gardemann, A., Keilhoff, G., Peter, D., Wiswedel, I., & Schild, L. (2012) · Phytomedicine · doi:10.1016/j.phymed.2011.12.002 · Cited by 46
The immunosuppressant drug, thalidomide, improves hepatic alterations induced by a high-fat diet in mice
Pinto, L. D. F., Compri, C. M., Fornari, J. V., Bartchewsky, W., Cintra, D. E., Trevisan, M. S., Carvalho, P. D. O., Ribeiro, M. L., Velloso, L. A., Saad, M. J. A., et al. (2010) · Liver International · doi:10.1111/j.1478-3231.2009.02200.x · Cited by 46
“In ob/ob mice, iNOS expression was increased in the liver and treatment with iNOS inhibitor reversed fasting hyperglycaemia and improved insulin sensitivity through enhanced IRS-mediated insulin signalling in the liver (28).”
Background
Luteolin is a bioflavonoid that attenuates adipocyte-derived inflammatory responses via suppression of nuclear factor-κB/mitogen-activated protein kinases pathway
Kim, D., Nepali, S., Son, J.-S., Poudel, B., Lee, J., & Lee, Y. (2015) · Pharmacognosy Magazine · doi:10.4103/0973-1296.160470 · Cited by 43
“It has been reported that iNOS is a key mediator of inflammation in obesity‐induced insulin resistance.[4,32] Figure 5: Luteolin inhibited protein expression of MCP-1 and interleukin (IL)-6”
Background
High-fructose corn syrup-induced hepatic dysfunction in rats: improving effect of resveratrol
Sadı, G., Ergin, V., Yılmaz, G., Pektaş, M. B., Yıldırım, O. G., Menevşe, A., & Akar, F. (2014) · European Journal of Nutrition · doi:10.1007/s00394-014-0765-1 · Cited by 43
Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion
Natali, A., Ribeiro, R. T., Baldi, S., Tulipani, A., Rossi, M., Venturi, E., Mari, A., Macedo, M. P., & Ferrannini, E. (2013) · Diabetologia · doi:10.1007/s00125-013-2836-x · Cited by 43
“Other studies showing a direct role of NO in inducing hepatic insulin resistance have used models in which excess NO was generated through liver-specific overexpression of the inducible nitric oxide synthase (NOS) isoform [11].”
Background
Altered glucose and lipid homeostasis in liver and adipose tissue pre-dispose inducible NOS knockout mice to insulin resistance
Kanuri, B., Kanshana, J. S., Rebello, S. C., Pathak, P., Gupta, A. P., Gayen, J. R., Jagavelu, K., & Dikshit, M. (2017) · Scientific Reports · doi:10.1038/srep41009 · Cited by 40
Nitrosative modifications of protein and lipid signaling molecules by reactive nitrogen species
White, P. J., Charbonneau, A., Cooney, G. J., & Marette, A. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00510.2010 · Cited by 49
“iNOS disruption was also found to partially prevent muscle insulin resistance in genetically obese ob/ob mice (117), whereas downregulation of iNOS by selective inhibitors or antisense oligonucleotides improved hepatic and muscle insulin action, respectively, in these animals (21, 40).”
Background
Role of AMP-activated Protein Kinase and Adiponectin during Development of Hepatic Steatosis in High-fat Diet-induced Obesity in Rats
Ha, S. K., Kim, J., & Chae, C. (2011) · Journal of Comparative Pathology · doi:10.1016/j.jcpa.2010.11.011 · Cited by 41
Deficiency of iNOS-derived NO accelerates lipid accumulation-independent liver fibrosis in non-alcoholic steatohepatitis mouse model
Nozaki, Y., Fujita, K., Wada, K., Yoneda, M., Kessoku, T., Shinohara, Y., Imajo, K., Ogawa, Y., Nakamuta, M., Saito, S., et al. (2015) · BMC Gastroenterology · doi:10.1186/s12876-015-0269-3 · Cited by 38
“Nitric oxide (NO) plays an important role in liver disease associated with IR and inflammation, and it has been reported that chronic and systemic deficiency of inducible nitric oxide synthase (iNOS) ameliorated high fat diet (HFD)-induced whole-body IR [5-7].”
Background
Brain-Defective Insulin Signaling Is Associated to Late Cognitive Impairment in Post-Septic Mice
Neves, F., Marques, P. T., Barros‐Aragão, F. G. Q., Nunes, J. B., Venancio, A. M., Cozachenco, D., Frozza, R. L., Passos, G. F., da Costa, R., de Oliveira, J., et al. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0307-3 · Cited by 40
Hepatic Lysosomal iNOS Activity Impairs Autophagy in Obesity
Qian, Q., Zhang, Z., Li, M., Savage, K., Cheng, D., Rauckhorst, A. J., Ankrum, J. A., Taylor, E. B., Ding, W., Xiao, Y., et al. (2019) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2019.03.005 · Cited by 38
The Inhibitory Effect of Tartary Buckwheat Extracts on Adipogenesis and Inflammatory Response
Lee, M.-S., Shin, Y., Jung, S., Kim, S.-Y., Jo, Y.-H., Kim, C., Yun, M., Lee, S.-J., Sohn, J., Yu, H.-J., et al. (2017) · Molecules · doi:10.3390/molecules22071160 · Cited by 37
“Moreover, rutin exerts protective effects on inflammatory diseases such as acute pancreatitis [54], diabetic cardiomyopathy [55], neuroinflammation [56] in vivo.”
Background
Pentoxifylline decreases glycemia levels and TNF-alpha, iNOS and COX-2 expressions in diabetic rat pancreas
Garcia, F. A. D. O., Pinto, S. F., Cavalcante, A. F., Lucetti, L. T., Menezes, S. M. S., Felipe, C. F. B., Alves, A. P. N., Brito, G. A. D. C., Cerqueira, G. S., & Viana, G. S. (2014) · SpringerPlus · doi:10.1186/2193-1801-3-283 · Cited by 39
“Furthermore, inducible nitric oxide synthase (iNOS) was shown to play a role in fasting hyperglycemia, contributing to hepatic insulin resistance, in a model of obese diabetic mice (Fujimoto et al. 2005).”
Background
Voluntary Exercise Can Ameliorate Insulin Resistance by Reducing iNOS-Mediated S-Nitrosylation of Akt in the Liver in Obese Rats
Tsuzuki, T., Shinozaki, S., Nakamoto, H., Kaneki, M., Goto, S., Shimokado, K., Kobayashi, H., & Naıto, H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0132029 · Cited by 35
“We and others have shown that inducible nitric oxide synthase (iNOS) inhibitor treatment improves insulin signaling at the level of insulin receptor substrate-1 (IRS-1) and -2 and Akt in the liver in genetically obese diabetic (ob/ob) mice [6, 7].”
Background
A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats
Stanimirović, J., Obradovic, M. M., Jovanović, A., Sudar-Milovanovic, E. M., Zafirovic, S. S., Pitt, S. J., Stewart, A. J., & Isenović, E. R. (2016) · Nitric Oxide · doi:10.1016/j.niox.2016.02.007 · Cited by 35
Farnesyltransferase Inhibitor, Manumycin A, Prevents Atherosclerosis Development and Reduces Oxidative Stress in Apolipoprotein E-Deficient Mice
Sugita, M., Sugita, H., & Kaneki, M. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.140673 · Cited by 35
Anti-Inflammatory and Antioxidant Properties of a New Arylidene-Thiazolidinedione in Macrophages
Faine, L. A., Rudnicki, M., de César, F. A., Heras, B. D. L., Boscá, L., Souza, É. S., Hernandes, M. Z., Galdino, S. L., de Lima, M. D. C. A., Pitta, I. D. R., et al. (2011) · Current Medicinal Chemistry · doi:10.2174/092986711796504600 · Cited by 37
“Interestingly, accumulating evidence indicates a close link between iNOS and insulin resistance [35].”
Background
Liver Sinusoidal Endothelial Cells Link Hyperinsulinemia to Hepatic Insulin Resistance
Tsuchiya, K., & Accili, D. (2013) · Diabetes · doi:10.2337/db12-1296 · Cited by 34
β -Sitosterol Shows Potential to Protect Against the Development of High-Fructose Diet-Induced Metabolic Dysfunction in Female Rats
Gumede, N. M., Lembede, B. W., Brooksbank, R. L., Erlwanger, K. H., & Chivandi, E. (2019) · Journal of Medicinal Food · doi:10.1089/jmf.2019.0120 · Cited by 33
Inducible nitric oxide synthase deficiency ameliorates skeletal muscle insulin resistance but does not alter unexpected lower blood glucose levels after burn injury in C57BL/6 mice
Sugita, M., Sugita, H., Kim, M., Mao, J., Yasuda, Y., Habiro, M., Shinozaki, S., Yasuhara, S., Shimizu, N., Martyn, J. A. J., et al. (2011) · Metabolism · doi:10.1016/j.metabol.2011.06.001 · Cited by 35
Obesity disrupts the pituitary-hepatic UPR communication leading to NAFLD progression
Qian, Q., Li, M., Zhang, Z., Davis, S. W., Rahmouni, K., Norris, A. W., Cao, H., Ding, W., Hotamışlıgil, G. S., & Yang, L. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.04.014 · Cited by 34
Redox Regulation of Insulin Degradation by Insulin-Degrading Enzyme
Cordes, C. M., Bennett, R. G., Siford, G. L., & Hamel, F. G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018138 · Cited by 34
“may result in locally increased iNOS expression and NO release [13,14,15,16,17].”
Background
Blocking iNOS and endoplasmic reticulum stress synergistically improves insulin resistance in mice
Zanotto, T. M., Quaresma, P. G. F., Guadagnini, D., Weissmann, L., Santos, A. C., Vecina, J. F., Calisto, K. L., Santos, A., Prada, P. O., & Saad, M. J. A. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.12.005 · Cited by 32
RETRACTED ARTICLE: TREM-1 associated macrophage polarization plays a significant role in inducing insulin resistance in obese population
Subramanian, S., Pallati, P. K., Sharma, P., Agrawal, D. K., & Nandipati, K. C. (2017) · Journal of Translational Medicine · doi:10.1186/s12967-017-1187-7 · Cited by 32
“Increased overexpression of CCR7 [38] and iNOS [39] in the obese diabetic group in a higher number of patients in omentum tissues compared to obese non-diabetics, suggests that the predominance of M1 macrophage markers in ATMs regulates the amplitude of adipose tissue inflammation.”
Background
Retracted
Nitric oxide dysregulates adipocytokine expression in 3T3-L1 adipocytes
野崎, 真., Fukuhara, A., Segawa, K., Okuno, Y., Abe, M., Hosogai, N., Matsuda, M., Komuro, R., & Shimomura, I. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.09.084 · Cited by 31
Association between Cardiovascular Disease and Liver Disease, from a Clinically Pragmatic Perspective as a Cardiologist
Nakashima, M., Nakamura, K., Nishihara, T., Ichikawa, K., Nakayama, R., Takaya, Y., Toh, N., Akagi, S., Miyoshi, T., Akagi, T., et al. (2023) · Nutrients · doi:10.3390/nu15030748 · Cited by 35
“The oxidative stress and inflammation, that are also associated with NAFLD as above mentioned, also cause endothelial vascular dysfunction [41,42], and these changes can also cause CVD in patients with NAFLD [43].”
Background
Changes in hepatic metabolic profile during the evolution of STZ-induced diabetic rats via an 1H NMR-based metabonomic investigation
Chen, M., Zheng, H. X., Xu, M., Zhao, L., Zhang, Q., Song, J., Zhao, Z., Lu, S., Weng, Q., Wu, X., et al. (2019) · Bioscience Reports · doi:10.1042/bsr20181379 · Cited by 30
Obesity, insulin resistance, and skeletal muscle nitric oxide synthase
Kraus, R. M., Houmard, J. A., Kraus, W. E., Tanner, C. J., Pierce, J. R., Choi, M. D., & Hickner, R. C. (2012) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01018.2011 · Cited by 28
“The present iNOS and insulin sensitivity results contradict previous reports that showed that insulin resistance was related to an elevation in skeletal muscle iNOS expression (11, 12, 21, 43, 53, 55, 58).”
BackgroundResult
Narrow-Leafed Lupin (Lupinus angustifolius L.) Seeds Gamma-Conglutin is an Anti-Inflammatory Protein Promoting Insulin Resistance Improvement and Oxidative Stress Amelioration in PANC-1 Pancreatic Cell-Line
Lima‐Cabello, E., Ramírez, J. D. D. A., Morales, S., Clemente, A., & Jiménez-López, J. C. (2019) · Antioxidants · doi:10.3390/antiox9010012 · Cited by 30
“, IR [38], promoting islet β-cell apoptosis [39] and the progression of diseases concomitant with inflammation [40].”
Background
Reduction in Embryonic Malformations and Alleviation of Endoplasmic Reticulum Stress by Nitric Oxide Synthase Inhibition in Diabetic Embryopathy
Zhao, Z., Eckert, R. L., & Reece, E. A. (2012) · Reproductive Sciences · doi:10.1177/1933719111434543 · Cited by 27
Quercetin Isolated from Toona sinensis Leaves Attenuates Hyperglycemia and Protects Hepatocytes in High-Carbohydrate/High-Fat Diet and Alloxan Induced Experimental Diabetic Mice
Zhang, Y., Dong, H., Wang, M., & Zhang, J. (2016) · Journal of Diabetes Research · doi:10.1155/2016/8492780 · Cited by 27
“It has been reported that diabetic mice had significantly increased levels of iNOS expression and activity in the serum [37, 38].”
Background

Authors: Fujimoto, M., Shimizu, N., Kunii, K., Martyn, J. A. J., Ueki, K., & Kaneki, M.
Affiliations: Harvard University (US)
The University of Tokyo (JP)
ORCID: Shimizu, Nobuyuki
Kunii, Kaiko
Martyn, J.A. Jeevendra
Ueki, Kohjiro
Kaneki, Masao
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2005-05-01
Volume: 54
Issue: 5
Pages: 1340-1348
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.54.5.1340
OpenAlex: W2138266804
Cited by: 209
References: 47
Citations by year: 2026: 3 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 11 · 2020: 9 · 2019: 15 · 2018: 12 · 2017: 10 · 2016: 10 · 2015: 24 · 2014: 14 · 2013: 7 · 2012: 15
FWCI: 4.32
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: Shriners Hospitals for Children
National Institutes of Health
National Institute of General Medical Sciences (R01GM055082, R01GM031569, R01GM061411)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058127)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Keywords: inducible nitric oxide synthase, fasting hyperglycemia, hepatic insulin resistance, insulin signaling, IRS-1, insulin receptor substrate 2, L-NIL, ob/ob mice, obesity, type 2 diabetes, nitric oxide, chronic inflammation, hepatocytes
MeSH terms: Animals, Cells, Cultured, Diabetes Mellitus, Type 2, Enzyme Inhibitors, Fasting, Hyperglycemia, Insulin, Insulin Resistance, Liver, Lysine, Male, Mice, Obese, Signal Transduction, Nitric Oxide Synthase, Phosphatidylinositol 3-Kinases, Nitric Oxide Donors, Hepatocytes, Mice, Nitric Oxide Synthase Type II

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A Role for iNOS in Fasting Hyperglycemia and Impaired Insulin Signaling in the Liver of Obese Diabetic Mice

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