Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/46187
Title: Elucidating the role of prolidase in impairment of insulin signaling via abnormalities in integrinβ1 signaling pathway.
Authors: Ng, Genevieve Gek Fong.
Keywords: DRNTU::Science::Biological sciences::Biochemistry
DRNTU::Science::Biological sciences::Human anatomy and physiology::Endocrinology
Issue Date: 2011
Abstract: 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.
URI: http://hdl.handle.net/10356/46187
Rights: Nanyang Technological University
Fulltext Permission: restricted
Fulltext Availability: With Fulltext
Appears in Collections:SBS Student Reports (FYP/IA/PA/PI)

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