Novel methodologies for the treatment of type 1 diabetes mellitus usingin silicotools

Epidemiologic studies reveal that the fight against diabetes is being lost, so to overcome this serious health problem every strategy should be taken seriously. Usingin silicodata we discuss the therapeutic potential for Diabetes Mellitus type 1 of two possible unstudied strategies; (I) ifINSULINparalog,INSULIN-INSULIN GROWTH FACTOR 2can be a regulator of glucose in humans, and (II) if extrapancreatic expression ofINSULINandINSULIN- INSULIN GROWTH FACTOR 2has any relevance in glucose regulation. To address this hypothesis, we access to the collection of protein sequences and gene expression from INSULIN and paralogues in EGB, NCBI and EBI. Phylogenetic and molecular evolutionary analyses were conducted using MEGA software, conserved protein motifs were compared using algorithm MUSCLE and presenting it graphically using CLC Genomics Workbench, transcripts and gene expression from transcriptome and microarray data from different experiments of insulin and paralogues were extracted and graphicaly presented using CIRCOS. Phylogenetic analysis revealed that humans, like most of all mammals, haveINSULINandINSULIN-INSULIN GROWTH FACTOR 2with the exception of murinae among mammals that shareInsulin 1andInsulin 2. BothInsulin 1 and 2can regulate glucose since both proteins are highly similar and with a redundant function, as confirmed byin vivoexperiments showing that both knockoutInsulin 1or2are normoglycemic. Human INSULIN- INSULIN GROWTH FACTOR 2 lacks motif 3 of the INSULIN signature, and part of the predicted protein structure does not present any known domain, making the prediction of a possible function for this gene inconclusive. Extrapancreatic expression of insulin has been observed in diabetic mice with contradictory effects, but available gene expression data in repository data banks also suggests that extrapancreatic expression of insulin occurs in human, mouse and zebrafish under basal condition. Gene expression DataSets demonstrate that extrapancreatic expression of INSULIN occurs under basal condition. Further investigation should be made, to understand if extrapancreatic expression of insulin can have a role in glucose homeostasis, as this could represent a complementary strategy in diabetes treatment.