Transcriptome meta-analysis of peripheral lymphomononuclear cells indicates that gestational diabetes is closer to type 1 diabetes than to type 2 diabetes mellitus.

We performed a meta-analysis of the transcription profiles of type 1, type 2 and gestational diabetes to evaluate similarities and dissimilarities among these diabetes types. cRNA samples obtained from peripheral blood lymphomononuclear cells (PBMC) of 56 diabetes mellitus patients (type 1 = 19; type 2 = 20; gestational = 17) were hybridized to the same whole human genome oligomicroarray platform, encompassing 44,000 transcripts. The GeneSpring software was used to perform analysis and hierarchical clustering, and the DAVID database was used for gene ontology. The gene expression profiles showed more similarity between gestational and type 1 diabetes rather than between type 2 and gestational diabetes, a finding that was not influenced by patient gender and age. The meta-analysis of the three types of diabetes disclosed 3,747 differentially and significantly expressed genes. A total of 486 genes were characteristic of gestational diabetes, 202 genes of type 1, and 651 genes of type 2 diabetes. 19 known genes were shared by type 1, type 2 and gestational diabetes, highlighting EGF, FAM46C, HBEGF, ID1, SH3BGRL2, VEPH1, and TMEM158 genes. The meta-analysis of PBMC transcription profiles characterized each type of diabetes revealing that gestational and type 1 diabetes were transcriptionally related.

Effects of angiotensin II, atrial natriuretic peptide and endothelin-1 on proliferation and steroidogenic output of bovine granulosa cells cultured in a chemically defined system.

The role of local factors in the modulation of granulosa cell (GC) proliferation and differentiation is well described in the literature. The present work used a long-term bovine GC culture, in chemically defined medium without gonadotropins, to study the effects of angiotensin II (Ang II), atrial natriuretic peptide (ANP) and endothelin-1 (EDN1) on the steroidogenesis and cellular proliferation. Small follicles (3-5mm in diameter) from ovaries obtained in the slaughterhouse were selected according to their vascularization and follicular fluid color in order to isolate GC. Granulosa cells were plated at a density of 5×10(4)cells/well in supplemented alpha-MEM containing 3 levels (0, 10(-8)M and 10(-7)M) of Ang II, ANP, and EDN1 for up to 96h. Proliferation was evaluated by tritiated thymidine incorporation. The results showed that Ang II, ANP, and EDN1 modulate the steroidogenic output and proliferation index of GCs depending on the dose and time of culture. The selected vasoactive peptides increased androstenedione (A4) consumption in parallel with increased estradiol (E2). Although the peptides also promoted a significant increase in pregnenolone (P5) and progesterone (P4) production, the E2:P4 ratio was maintained at a high at most of the tested doses. Taken together, our in vitro data suggest that these vasoactive factors may have a direct effect on physiological follicular deviation, favoring dominance of the selected follicle.