Sites and mechanisms of insulin resistance in nonobese, nondiabetic patients with chronic hepatitis C. Export

@article{citeulike:6066278, abstract = {Chronic hepatitis C (CHC) has been associated with type 2 diabetes and insulin resistance, but the extent of impairment in insulin action, the target pathways involved, and the role of the virus per se have not been defined. In this study, we performed a euglycemic hyperinsulinemic clamp (1 mU x minute(-1) x kg(-1)) coupled with infusion of tracers ([6,6-(2)H(2)]glucose, [(2)H(5)]glycerol) and indirect calorimetry in 14 patients with biopsy-proven CHC, who were selected not to have any features of the metabolic syndrome, and in seven healthy controls. We also measured liver expression of inflammatory cytokines/mediators and tested their association with the metabolic parameters. Compared to controls, in patients with CHC: (1) total glucose disposal (TGD) during the clamp was 25\% lower (P = 0.003) due to impaired glucose oxidation (P = 0.0002), (2) basal endogenous glucose production (EGP) was 20\% higher (P = 0.011) and its suppression during the clamp was markedly reduced (P = 0.007), and (3) glycerol appearance was not different in the basal state or during the clamp, but lipid oxidation was less suppressed by insulin (P = 0.004). Lipid oxidation was higher in patients with CHC who had more steatosis and was directly related to EGP, TGD, and glucose oxidation. The decreased insulin-stimulated suppression of EGP was associated with increased hepatic suppressor of cytokine signaling 3 (SOCS3; P < 0.05) and interleukin-18 (P < 0.05) expression. Conclusion: Hepatitis C infection per se is associated with peripheral and hepatic insulin resistance. Substrate competition by increased lipid oxidation and possibly enhanced hepatic expression of inflammatory cytokines/mediators could be involved in the defective glucose regulation.}, author = {Vanni, Ester and Abate, Maria Lorena L. and Gentilcore, Elena and Hickman, Ingrid and Gambino, Roberto and Cassader, Maurizio and Smedile, Antonina and Ferrannini, Ele and Rizzetto, Mario and Marchesini, Giulio and Gastaldelli, Amalia and Bugianesi, Elisabetta}, citeulike-article-id = {6066278}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/hep.23031}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19582803}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19582803}, doi = {10.1002/hep.23031}, issn = {1527-3350}, journal = {Hepatology (Baltimore, Md.)}, keywords = {hcv, irs}, month = {September}, number = {3}, pages = {697--706}, posted-at = {2009-11-04 04:23:38}, priority = {2}, title = {Sites and mechanisms of insulin resistance in nonobese, nondiabetic patients with chronic hepatitis C.}, url = {http://dx.doi.org/10.1002/hep.23031}, volume = {50}, year = {2009} }

TY - JOUR ID - citeulike:6066278 L3 - citeulike-article-id:6066278 N2 - Chronic hepatitis C (CHC) has been associated with type 2 diabetes and insulin resistance, but the extent of impairment in insulin action, the target pathways involved, and the role of the virus per se have not been defined. In this study, we performed a euglycemic hyperinsulinemic clamp (1 mU x minute(-1) x kg(-1)) coupled with infusion of tracers ([6,6-(2)H(2)]glucose, [(2)H(5)]glycerol) and indirect calorimetry in 14 patients with biopsy-proven CHC, who were selected not to have any features of the metabolic syndrome, and in seven healthy controls. We also measured liver expression of inflammatory cytokines/mediators and tested their association with the metabolic parameters. Compared to controls, in patients with CHC: (1) total glucose disposal (TGD) during the clamp was 25% lower (P = 0.003) due to impaired glucose oxidation (P = 0.0002), (2) basal endogenous glucose production (EGP) was 20% higher (P = 0.011) and its suppression during the clamp was markedly reduced (P = 0.007), and (3) glycerol appearance was not different in the basal state or during the clamp, but lipid oxidation was less suppressed by insulin (P = 0.004). Lipid oxidation was higher in patients with CHC who had more steatosis and was directly related to EGP, TGD, and glucose oxidation. The decreased insulin-stimulated suppression of EGP was associated with increased hepatic suppressor of cytokine signaling 3 (SOCS3; P < 0.05) and interleukin-18 (P < 0.05) expression. Conclusion: Hepatitis C infection per se is associated with peripheral and hepatic insulin resistance. Substrate competition by increased lipid oxidation and possibly enhanced hepatic expression of inflammatory cytokines/mediators could be involved in the defective glucose regulation. IS - 3 JF - Hepatology (Baltimore, Md.) SN - 1527-3350 EP - 706 TI - Sites and mechanisms of insulin resistance in nonobese, nondiabetic patients with chronic hepatitis C. VL - 50 SP - 697 KW - hcv KW - irs AU - Vanni, Ester AU - Abate, Maria Lorena AU - Gentilcore, Elena AU - Hickman, Ingrid AU - Gambino, Roberto AU - Cassader, Maurizio AU - Smedile, Antonina AU - Ferrannini, Ele AU - Rizzetto, Mario AU - Marchesini, Giulio AU - Gastaldelli, Amalia AU - Bugianesi, Elisabetta PY - 2009/09// UR - http://dx.doi.org/10.1002/hep.23031 ER -