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Objective: There is evidence that monocytes of patients with type 1 diabetes show proinflammatory activation and disturbed migration/adhesion, but the evidence is inconsistent. Our hypothesis is that monocytes are distinctly activated/disturbed in different subforms of autoimmune diabetes., Research Design and Methods: We studied patterns of inflammatory gene expression in monocytes of patients with type 1 diabetes (juvenile onset, n = 30; adult onset, n = 30) and latent autoimmune diabetes of the adult (LADA) (n = 30) (controls subjects, n = 49; type 2 diabetic patients, n = 30) using quantitative PCR. We tested 25 selected genes: 12 genes detected in a prestudy via whole-genome analyses plus an additional 13 genes identified as part of a monocyte inflammatory signature previously reported., Results: We identified two distinct monocyte gene expression clusters in autoimmune diabetes. One cluster (comprising 12 proinflammatory cytokine/compound genes with a putative key gene PDE4B) was detected in 60% of LADA and 28% of adult-onset type 1 diabetic patients but in only 10% of juvenile-onset type 1 diabetic patients. A second cluster (comprising 10 chemotaxis, adhesion, motility, and metabolism genes) was detected in 43% of juvenile-onset type 1 diabetic and 33% of LADA patients but in only 9% of adult-onset type 1 diabetic patients., Conclusions: Subgroups of type 1 diabetic patients show an abnormal monocyte gene expression with two profiles, supporting a concept of heterogeneity in the pathogenesis of autoimmune diabetes only partly overlapping with the presently known diagnostic categories.

Background: In cardiomyocytes and cardiac fibroblasts, stretch induces a growth response., Methods: To investigate which signal transduction pathways are involved in the stretch-induced growth response of cardiomyocytes and cardiac fibroblasts, we used a model of mechanical stress in which cells are submitted to biaxial cyclic stretch., Results: In stretched cardiomyocytes major bands of tyrosine-phosphorylated (P-Tyr) proteins of 58, 49, and 27 kDa were detected and minor bands of 65 and 40 kDa. Furthermore, major bands of serine/threonine phosphorylated (P-Ser/Thr) proteins of 46, 42, and 21 kDa were detected. Phosphorylation of the 40 kDa P-Tyr protein increased significantly upon stretch. In cardiac fibroblasts major bands of P-Tyr proteins of 63, 53, and 23 kDa were detected and minor bands of 72 and 39 kDa. In addition, major bands of P-Ser/Thr proteins of 51, 47, and 23 kDa were detected and minor bands of 54 and 33 kDa. Phosphorylation of the 54 and 33 kDa P-Ser/Thr proteins increased significantly upon stretch. Phosphorylated JNK 1 and JNK 2 activities were not detected in fibroblasts. In cardiomyocytes levels of phosphorylated JNK 1 and 2 were very low, but tend to increase upon stretch. Phosphorylated p38 MAPK could not be identified in both cell types. The intensity of phosphorylation of paxillin increased upon stretch in both cell types, although the increases were only significantly different in stretched fibroblasts. Finally, stretch increased PLC activity in cardiomyocytes as well as in fibroblasts., Conclusion: Our findings are in favour of mechanotransduction of the stretch signal via integrins and focal adhesion components such as FAK, Src kinase, PLC and paxillin. The activation of the last two focal adhesion components by stretch of cardiomyocytes and fibroblasts is demonstrated in this article.