ABSTRACT
AIMS/HYPOTHESIS: Insulin action is purportedly modulated by Drosophila tribbles homologue 3 (TRIB3), which in vitro prevents thymoma viral proto-oncogene (AKT) and peroxisome proliferator-activated receptor-γ (PPAR-γ) activation. However, the physiological impact of TRIB3 action in vivo remains controversial. METHODS: We investigated the role of TRIB3 in rats treated with either a control or Trib3 antisense oligonucleotide (ASO). Tissue-specific insulin sensitivity was assessed in vivo using a euglycaemic-hyperinsulinaemic clamp. A separate group was treated with the PPAR-γ antagonist bisphenol-A-diglycidyl ether (BADGE) to assess the role of PPAR-γ in mediating the response to Trib3 ASO. RESULTS: Trib3 ASO treatment specifically reduced Trib3 expression by 70% to 80% in liver and white adipose tissue. Fasting plasma glucose, insulin concentrations and basal rate of endogenous glucose production were unchanged. However, Trib3 ASO increased insulin-stimulated whole-body glucose uptake by ~50% during the euglycaemic-hyperinsulinaemic clamp. This was attributable to improved skeletal muscle glucose uptake. Despite the reduction of Trib3 expression, AKT2 activity was not increased. Trib3 ASO increased white adipose tissue mass by 70% and expression of Ppar-γ and its key target genes, raising the possibility that Trib3 ASO improves insulin sensitivity primarily in a PPAR-γ-dependent manner. Co-treatment with BADGE blunted the expansion of white adipose tissue and abrogated the insulin-sensitising effects of Trib3 ASO. Finally, Trib3 ASO also increased plasma HDL-cholesterol, a change that persisted with BADGE co-treatment. CONCLUSIONS/INTERPRETATION: These data suggest that TRIB3 inhibition improves insulin sensitivity in vivo primarily in a PPAR-γ-dependent manner and without any change in AKT2 activity.
Subject(s)
Insulin Resistance/physiology , PPAR gamma/metabolism , Protein Kinases/metabolism , Animals , Benzhydryl Compounds , Diabetes Mellitus, Type 2/metabolism , Disease Models, Animal , Epoxy Compounds/pharmacology , Glucose Clamp Technique , Immunoblotting , Insulin Resistance/genetics , Male , Oligonucleotides, Antisense/genetics , PPAR gamma/antagonists & inhibitors , PPAR gamma/genetics , Protein Kinases/genetics , Protein Serine-Threonine Kinases/antagonists & inhibitors , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Samples of 293 students of European heritage and 102 students of African heritage completed the Revised Death Anxiety Scale. Euro-Americans were more concerned with the uncertainty associated with death and with the loss of being, while African Americans expressed greater anxiety over the pain associated with dying, but there was no significant mean difference in total scores for the groups.
Subject(s)
Anxiety/diagnosis , Attitude to Death , Black or African American/psychology , Personality Inventory/statistics & numerical data , White People/psychology , Adolescent , Adult , Anxiety/psychology , Cross-Cultural Comparison , Female , Humans , Male , PsychometricsABSTRACT
Samples of 83 younger and 52 older African-American women completed a death anxiety scale; the younger women had significantly higher scores on the total scale, principally on items dealing with pain, loss of bodily integrity, and decomposition.
