Knockdown of the gene encoding Drosophila tribbles homologue 3 (Trib3) improves insulin sensitivity through peroxisome proliferator-activated receptor-γ (PPAR-γ) activation in a rat model of insulin resistance.

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.

[Cytomegalovirus infection in neonate--report of two cases].

The cytomegalovirus (CMV) is an abiquitous agent that infects almost all human beings at some time during their lives. In developing area of the world, 90% or more of the population is infected during childhood. However, in developed countries the infection is acquired at a lower rate. In neonates, CMV infection can be divided into congenital and perinatal infection. Congenital CMV infection is the result of transplacental transmission, CMV can be transmitted to the fetus following reactivation as well as primary infection during pregnancy. The incidence of congenital infection is 0.2% to 2.2%. Symptomatic congenital CMV infection is more likely to be the result of primary as opposed to reactive CMV infection during pregnancy. The clinical manifestations of symptomatic CMV infection are hepatosplenomegaly, microcephaly, jaundice, petechiae, small for gestation age, periventricular calcification and chorioretinitis. Mortality may be as high as 30% among the most severely affected infants. In the survivors, about 90% will develop mild to severe handicaps. Perinatal CMV infection can be acquired from exposure to virus in the maternal genital tract at delivery, breast milk, or through blood transfusion. In premature infants who require prolonged and intensive medical care, blood transfusions are an important iatrogenic cause of CMV infection. Transfusion-acquired perinatal CMV infection can cause significant morbidity and mortality, particularly in premature infants with a birth weight of less than 1250 gm born to CMV-seronegative mothers. So CMV acquisition can be prevented either by providing these infants blood products from seronegative donors or by using frozen deglycerolized red blood cells. Two cases of neonatal CMV infection are reported, one with congenital infection, the other with perinatal infection.