Article thumbnail

Rosiglitazone-Mediated Effects on Skeletal Muscle Gene Expression Correlate with Improvements in Insulin Sensitivity in Individuals with HIV-Insulin Resistance

By Dennis C. Mynarcik, Margaret A. McNurlan, Mark M. Melendez, James A. Vosswinkel and Marie C. Gelato

Abstract

Rosiglitazone, an agonist of peroxisome proliferator activated receptor (PPARγ), improves insulin sensitivity by increasing insulin-stimulated glucose uptake into muscle tissue. This study was undertaken to assess changes in expression of PPAR-regulated genes in muscle tissue following treatment of HIV-associated insulin resistance with rosiglitazone. Muscle gene expression was assessed in twenty-two seronegative HIV subjects (control), 21 HIV-infected individuals with normal insulin sensitivity (HIV-IS) and 19 HIV-infected individuals with insulin resistance (HIV-IR). A subset of the HIV-IR group (N = 10) were re-evaluated 12 weeks after treatment with 8 mg/d of rosiglitazone. The HIV-IR group's rosiglitazone-mediated improvement in insulin sensitivity was highly correlated with increased expression of PPARγ and carnitine palmitoyl transferase-1 (CPT-1), (r = 0.87, P < .001) and (r = 0.95, P < .001), respectively. The changes in PPARγ expression were also correlated with the changes in CPT1 expression (r = 0.75, P = .009). The results suggest that rosiglitazone; may have a direct effect on muscle tissue to improve insulin sensitivity

Topics: Research Article
Publisher: SAGE-Hindawi Access to Research
OAI identifier: oai:pubmedcentral.nih.gov:3090220
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. (2003). 5-Aryl thiazolidine2,4-dionesasselective PPARγ agonists,”Bioorganic andMedicinal
  2. (2002). A .H .B e r g ,T .P .C o m b s ,a n dP .E .S c h e r e r , “ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism,”
  3. (2007). a m a u c h i ,Y .N i o ,T .M a k ie ta l . ,“ T a r g e t e dd i s r u p t i o n of
  4. (1998). A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors,”
  5. (2006). Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network,”
  6. (2005). andU.Smith,“Improved insulinsensitivityandadipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic,
  7. (1996). Body fat distribution and the distribution and the distribution of scientific knowledge,”
  8. (2006). Calles-Escandon et al., “Differential effects of contraction and PPAR agonists on the expression of fatty acid transporters in rat skeletal muscle,”
  9. (2003). Cardiovascular disease risk factors in HIV patients—association with antiretroviral therapy.
  10. (2004). Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity,” J o u r n a lo fB i o l o g i c a lC h e m i s t r y ,
  11. (2001). Comprehensive messenger ribonucleic acid profiling reveals that peroxisome proliferator-activated receptor γ activation has coordinate effects on gene expression in multiple insulinsensitive tissues,”
  12. (1981). D e F r o n z o ,E .J a c o t ,E .J e q u i e r ,E .M a e d e r ,J .W a h r e n , a n dJ
  13. (1999). Diagnosis, prediction, and naturalcourseofHIV-1protease-inhibitor-associatedlipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study,”
  14. (2003). Differential effects of rosiglitazone on skeletal muscle and liver insulin resistance
  15. (2000). Distribution of peroxisome proliferator-activated receptors (PPARs) in human skeletal muscle and adipose tissue: relation to insulin action,”
  16. (1998). Dyslipoproteinemia and diabetes,” Endocrinology and Metabolism Clinics of
  17. (2005). e i m a n d i ,G .L e m a i r e ,A .P i l l o ne ta l . ,“ D i fferential responses of PPARα,P
  18. (2004). Effect of pioglitazone on circulating adipocytokine levels and insulin sensitivity in type 2 diabetic patients,”
  19. (2004). Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy,”
  20. (1999). Fasting hyperinsulinemia and changes in regional body composition in human immunodeficiency virus-infected women,”
  21. (1979). Fiber composition,fiber sizeandenzymeactivities in vastuslateralis of elite athletes involved in high intensity exercise,”
  22. (2000). Fiber type composition of the vastus lateralis muscle of young men and women,”
  23. (2002). G e l a t o ,D .C .M y n a r c i k ,J .L .Q u i c ke ta l . ,“ I m p r o v e d insulin sensitivity and body fat distribution in HIV-infected patients treated with rosiglitazone: a pilot study,”
  24. (1979). Glucose clamp technique: a method for quantifying insulin secretion and resistance,” The American journal of physiology,
  25. (1997). H a ffner, “Impaired glucose tolerance—is it relevant for cardiovascular disease?”
  26. (2002). h r e n s ,A .R .B o e r n e r ,K .W e b e re ta l . ,“ I m p a i r e d glucose phosphorylation and transport in skeletal muscle cause insulin resistance in HIV-1-infected patients with lipodystrophy,”
  27. (2004). Human skeletal muscle PPARα expression correlates with fat metabolism gene expression but not BMI or insulin sensitivity,”
  28. (1996). Hyperinsulinemia as an independent risk factor for ischemic heart disease,” TheNewEnglandJournal ofMedicine,vol.334,no.15,pp.952– 957,
  29. (2000). Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection,”
  30. (2004). J.Tonelli,W.Li,P.Kishoreetal.,“Mechanismsofearlyinsulinsensitizing effects of thiazolidinediones
  31. (2005). K a z e m i ,P .Y .H s u ee ta l . ,“ T h er e l a t i o n s h i p between nucleosicle analogue treatment duration,
  32. (2006). Kroidl et al., “Evaluation of safety and efficacy of rosiglitazone in the treatment of HIV-associated lipodystrophy syndrome,”
  33. (2000). M y n a r c i k ,M .A .M c N u r l a n ,R .T .S t e i g b i g e l ,J .F u h r e r , andM.C.Gelato,“Associationofsevereinsulinresistancewith both loss of limb fat and elevated serum tumor necrosis factor receptor levels in HIV lipodystrophy,”
  34. (1998). Malonyl CoA, longchain fatty acyl CoA and insulin resistance in skeletal muscle,”
  35. (2004). Metabolic effects of rosiglitazone in HIV lipodystrophy: a randomized, controlled trial,”
  36. (2000). Metformin in the treatment of HIV lipodystrophy syndrome: a randomized controlled trial,”
  37. (2006). Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor γ agonists,”
  38. (2003). Muscle-specific Pparg deletion causes insulin resistance,”
  39. (1999). Mykk¨ anen et al., “Insulin sensitivity in subjects with type 2 diabetes: relationship to cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study,” Diabetes Care,
  40. (2004). No effect of rosiglitazonefortreatmentofHIV-1lipoatrophy:randomised, double-blind,
  41. (1997). PPAR-γ gene expression is elevated in skeletal muscle of obese and II diabetic subjects,”
  42. (1999). PPARγ is required for the differentiation of adipose tissue in vivo and in vitro,”
  43. (1996). r a i s s a n t ,F .F o u f e l l e ,C .S c o t t o ,M .D a u c ¸a, and W. Wahli, “Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-α,- β,a n d- γ in the adult rat,”
  44. (1997). Rasp´ ee ta l . ,“ T h eo r g a n i z a t i o n , promoteranalysis,andexpression ofthe humanPPARγ gene,” J o u r n a lo fB i o l o g i c a lC h e m i s t r y ,
  45. (2000). Regulation of fatty acid transporters in mammalian cells,”
  46. (1984). Relationship between skeletal muscle insulin resistance, insulin mediated glucose disposal, and insulin binding. Effects of obesity and body fat topography,”
  47. (2003). Rosiglitazone in the treatment of HAART-associated lipodystrophy—a randomized double-blind placebo-controlled study,”
  48. (2003). Thiazolidinediones upregulate impaired fatty acid uptake in skeletal muscleof type 2 diabetic subjects,”
  49. Tomaˇ ziˇ c ,P .K a r n e r ,L .V i d m a r ,M .M a t i ˇ ciˇ
  50. (1981). Use of a heated superficial hand vein as an alternative site for the measurement of amino acid concentrations and for the study of glucose and alanine kinetics in man,”
  51. (2005). V a nW i j k ,E .J .D eK o n i n g ,M .C .C a b e z a s ,J .O p ’ tR o o d t
  52. (1998). W i s e ,M .F .N i e l s e n ,P .E .C r y e r ,a n dR .A .R i z z a , “Overnightnormalizationofglucoseconcentrationsimproves hepatic but not extrahepatic insulin action in subjects with type 2 diabetes mellitus,”