ABSTRACT
<p><b>OBJECTIVE</b>To review the current advances on the role of uncoupling protein (UCP) in the pathogenesis and progress of nonalcoholic fatty liver disease (NAFLD).</p><p><b>DATA SOURCES</b>A comprehensive search of the PubMed literature without restriction on the publication date was carried out using keywords such as UCP and NAFLD.</p><p><b>STUDY SELECTION</b>Articles containing information related to NAFLD and UCP were selected and carefully analyzed.</p><p><b>RESULTS</b>The typical concepts, up-to-date findings, and existing controversies of UCP2 in NAFLD were summarized. Besides, the effect of a novel subtype of UCP (hepatocellular down regulated mitochondrial carrier protein, HDMCP) in NAFLD was also analyzed. Finally, the concept that any mitochondrial inner membrane carrier protein may have, more or less, the uncoupling ability was reinforced.</p><p><b>CONCLUSIONS</b>Considering the importance of NAFLD in clinics and UCP in energy metabolism, we believe that this review may raise research enthusiasm on the effect of UCP in NAFLD and provide a novel mechanism and therapeutic target for NAFLD.</p>
Subject(s)
Animals , Humans , Fatty Acids, Nonesterified , Metabolism , Fatty Liver , Metabolism , Ion Channels , Physiology , Mitochondrial Proteins , Chemistry , Physiology , Non-alcoholic Fatty Liver Disease , Uncoupling Protein 2ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of various HIV protease inhibitors on the function of pancreatic beta-cells.</p><p><b>METHODS</b>Rat insulinoma INS-1 cells were incubated with different concentrations of ritonavir or amprenavir for 48 h and stimulated with 20 mmol/L D-glucose for 30 min. The rate of insulin release was measured in the supernatant by ELISA, normalized to cellular DNA contents. Cells were counted with trypan blue and MTT test were determined to evaluate the effect of protease inhibitors on cell viability.</p><p><b>RESULT</b>Ritonavir treatment significantly decreased baseline insulin release and glucose-stimulated insulin release in a dose-dependent manner (r=-0.861, -0.839, both P<0.01). For 10 micromol/L of ritonavir, the decrease rate of baseline insulin secretion and glucose-stimulated insulin secretion was 46% and 47%, respectively. Amprenavir had no effect on the rate of insulin release.</p><p><b>CONCLUSION</b>Various HIV protease inhibitors present different effect on the insulin release of pancreatic beta-cells.</p>
Subject(s)
Animals , Rats , Carbamates , Pharmacology , HIV Protease Inhibitors , Pharmacology , Insulin , Bodily Secretions , Insulinoma , Metabolism , Pathology , Islets of Langerhans , Metabolism , Pancreatic Neoplasms , Metabolism , Pathology , Ritonavir , Pharmacology , Sulfonamides , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To investigate whether HIV-1 protease inhibitor nelfinavir alters the insulin stimulated phosphorylation of insulin signaling parameters in rat insulinoma INS-1 cells.</p><p><b>METHODS</b>INS-1 cells were incubated with nelfinavir for 48 h and stimulated with 100 nmol/L insulin for 2 min. Immunoprecipitation and Western blot analysis of the insulin stimulated insulin receptor substrate (IRS)-1,-2 and Akt-Thr(308) phosphorylation were performed on cell lysates. Cytotoxic effects of nelfinavir were measured by cell count with trypan blue and MTT reduction test.</p><p><b>RESULT</b>Nelfinavir decreased insulin stimulated phosphorylation of IRS-2 and Akt-Thr(308) in a dose-dependent manner; for 10 micromol/L of nelfinavir, the decrease was 52% and 55%, respectively.</p><p><b>CONCLUSION</b>Treatment with nelfinavir might impair IRS-2-mediated signaling in pancreatic beta cells.</p>