title: The acute effects of HIV protease inhibitors on insulin suppression of glucose production in healthy HIV-negative men.
abstract: BACKGROUND
  The effects of different HIV protease inhibitors (PIs) on peripheral insulin resistance have been described, but less is known about their effects on insulin suppression of endogenous glucose production (EGP).
  
  
  METHODS
  We tested the acute effects of 3 PIs, indinavir, ritonavir, and amprenavir, on EGP quantified by stable isotope techniques during the hyperinsulinemic, euglycemic clamp in 3 similar placebo-controlled protocols.
  
  
  RESULTS
  EGP was higher with indinavir in the hyperinsulinemic state than with placebo (4.1 +/- 1.3 vs. 2.2 +/- 0.8 microg x kg(-1) x min(-1), P = 0.04). A trend toward higher EGP was seen with ritonavir (3.6 +/- 0.3 vs. 3.0 +/- 0.5 microg x kg(-1) x min(-1), P = 0.08). There was no evidence that amprenavir blunted insulin suppression of EGP compared with placebo (2.9 +/- 0.04 vs. 3.2 +/- 0.7 microg x kg(-1) x min(-1), P = 0.63).
  
  
  CONCLUSIONS
  Some PIs can acutely blunt the ability of insulin to suppress EGP, but, as with insulin resistance, the effects of PIs on EGP are drug-specific, not class-specific.
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Grace A
authors.initials: GA
authors.lastname: Lee
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Schwarz
authors.forename: Sophie
authors.initials: S
authors.lastname: Patzek
authors.forename: Seungki
authors.initials: S
authors.lastname: Kim
authors.forename: Artem
authors.initials: A
authors.lastname: Dyachenko
authors.forename: Michael
authors.initials: M
authors.lastname: Wen
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mulligan
authors.forename: Morris
authors.initials: M
authors.lastname: Schambelan
authors.forename: Carl
authors.initials: C
authors.lastname: Grunfeld
mesh_terms: D002219:Carbamates / Q000009:adverse effects*; D005663:Furans; D005947:Glucose / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D006805:Human Experimentation; D006801:Humans; D019469:Indinavir / Q000009:adverse effects*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D019438:Ritonavir / Q000009:adverse effects*; D013449:Sulfonamides / Q000009:adverse effects*
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D007328:Insulin; D010919:Placebos; D013449:Sulfonamides; C095108:amprenavir; D019469:Indinavir; D005947:Glucose; D019438:Ritonavir
references.citation: AIDS. 2004 Sep 3;18(13):1852-4
references.pmid: 15316349
references.citation: AIDS. 2002 Mar 29;16(5):F1-8
references.pmid: 11964551
references.citation: Diabetes. 2003 Jul;52(7):1695-1700
references.pmid: 12829635
references.citation: Metabolism. 1988 Jan;37(1):15-21
references.pmid: 3275857
references.citation: AIDS. 2001 May 4;15(7):F11-8
references.pmid: 11399973
references.citation: J Clin Invest. 1985 Jul;76(1):149-55
references.pmid: 3894418
references.citation: J Clin Invest. 2004 Dec;114(11):1666-75
references.pmid: 15578099
references.citation: AIDS. 2002 Apr 12;16(6):859-63
references.pmid: 11919487
references.citation: AIDS. 2007 Oct 18;21(16):2183-90
references.pmid: 18090045