ABSTRACT
PURPOSE: Gestational diabetes is associated with increased risk to the health of the mother and her offspring. In particular, the infants of diabetic mothers (IDMs) exhibit elevated levels of preterm birth, macrosomia, hypoglycemia, hypocalcemia, and cardiomyopathy. We have previously reported that IDMs showed abnormalities in cardiac Akt-related insulin signalling, and that these deficiencies in Akt-related signalling were attenuated by supplementing the maternal diet with fish-oil. Herein, we investigated whether the eicosapentaenoic acid (EPA) found in fish oil can be used to attenuate diabetes associated impairments in cardiomyocyte signalling. METHODS: Pregnant diabetic rats were administered streptozotocin before receiving EPA or water, and their infants were designated IDM/EPA, IDM/W. We assessed the potential molecular pathway for this effect in the primary cardiac cell from newborn rat hearts. RESULTS: Insulin resistance as determined by diminished GLUT4 translocation following insulin stimulation, the levels of advanced glycation end products (AGEs) and reactive oxygen species were elevated in the neonatal hearts of IDM/W compared with that seen in the offspring born from non-diabetic control animals. Similarly, the receptor of AGEs (RAGE) mRNA levels, reactive oxygen species and the amount of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) mRNA were higher in the hearts from the IDM/W when compared to that observed in the hearts of offspring born to non-diabetic animals. These deleterious effects of gestational diabetes were significantly decreased in the offspring of diabetic mothers receiving EPA supplementation. CONCLUSIONS: Taken together, our data suggest that the EPA in fish oil may improve the impaired signalling and the excessive protein glycation in the cardiac muscles of infants exposed to intrauterine hyperglycemia.
Subject(s)
Animals, Newborn , Diabetes Mellitus, Experimental/metabolism , Hyperglycemia/drug therapy , Myocardium/metabolism , Receptor for Advanced Glycation End Products/metabolism , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/drug therapy , Diabetes, Gestational/drug therapy , Eicosapentaenoic Acid/pharmacology , Female , Fish Oils/pharmacology , Glucose Transporter Type 4/genetics , Glucose Transporter Type 4/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Oxidative Stress/drug effects , Pregnancy , Rats , Reactive Oxygen Species/metabolism , Receptor for Advanced Glycation End Products/genetics , Signal Transduction , Triglycerides/blood , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
A novel phospholipase A(2) (PLA(2)) gene, named PfPLA 6, was found in a 6,328-bp NIS-1(5')-a segment in the Protobothrops flavoviridis (Habu, Crotalinae) genome. A comparison of the aligned nucleotide sequences of Viperidae (Viperinae and Crotalinae) venom PLA(2) genes, including PfPLA 6, revealed the deletion of a 12-bp segment called S1EX 1 and a 55-bp segment called S2EX 1 in exon 1 and the interposition of a 219-bp segment called SINT 2 (SINE) in intron 2. A classification of Viperidae PLA(2) genes based on these structural modes indicated that the A-type genes (without SINE), including PfPLA 6, are evolutionarily ancestral to the B-type (Viperinae) and C-type (Crotalinae) PLA(2) genes (both with SINE). Since PfPLA 6 is a pseudogene, an active prototype of PfPLA 6 can be assumed to be the ancestral PLA(2) gene. Putative evolutionary processes from this A-type prototype PLA(2) gene to descendent PLA(2) genes are discussed.
