| الملخص: | In this research project, novel gene PEPD encoding for prolidase enzyme was found
to be linked to Type 2 Diabetes Mellitus. We investigated the 1) differences in PEPD
mRNA and protein expression in insulin-sensitive versus insulin-resistant muscle
samples; and if 2) associated prolidase, integrinβ1, PKB and GLUT4 expression
levels are altered. Western blots demonstrated increased PEPD expression in
insulin-resistant subjects with no visble change in associated integrinβ1 receptor
expression. Likewise, collagen staining done on myocytes illustrated higher collagen
concentration in insulin-resistant samples. Fibronectin was used as a positive
marker to verify that increased collagen resynthesis led to alterations in cytoskeletal density. This supports the hypothesis that PEPD upregulation is at least partially responsible for the modification of cytoskeletal components. As networks within a cell system are interconnected, the tensegrity of cytoskeleton is thought to influence the state of signalling components and impact cellular signalling mechanisms and pathways. We next studied the involvement of integrinβ1-receptor-associated
signalling pathways, particularly the PKC and PKB/Akt pathway, in the cytoskeleton
of IR subjects. There we established a decrease in PKCtheta/zeta expression and an
upregulation of Ser-Thr-PKB/Akt activity in IR subjects, both of which are signalling
pathways that can mediate impairment of glucose-transport in skeletal muscle.
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