Landscape mapping of functional proteins in insulin signal transduction and insulin resistance: a network-based protein-protein interaction analysis

Abstract

The type 2 diabetes has increased rapidly in recent years throughout the world. The insulin signal transduction mechanism gets disrupted sometimes and it's known as insulin-resistance. It is one of the primary causes associated with type-2 diabetes. The signaling mechanisms involved several proteins that include 7 major functional proteins such as INS, INSR, IRS1, IRS2, PIK3CA, Akt2, and GLUT4. Using these 7 principal proteins, multiple sequences alignment has been created. The scores between sequences also have been developed. We have constructed a phylogenetic tree and modified it with node and distance. Besides, we have generated sequence logos and ultimately developed the protein-protein interaction network. The small insulin signal transduction protein arrangement shows complex network between the functional proteins.

Figure 1. Insulin signal transduction pathway.

The damage of insulin signal transduction causes insulin resistance, which is one of the main causes for type 2 diabetes.

Figure 2. Alignment scores of protein sequences related to insulin resistance pathways.

(A) Alignment score between sequences (notation Seq (x:y) meaning alignment score between sequence x, and sequence y), (B) scatter distribution of scores, and (C) scores connected by smoothed line without marker.

Figure 3. Phylogenetic tree construction using ClustalW.

Figure 4. Distance of the phylogenetic tree of 12 nodes (developed by MATLAB 7.3).

Figure 5. Ribbon like structure of the main functional proteins associated with pathway.

Collected from Protein Data Bank.

Figure 6. Main proteins associated with insulin signaling pathway.

Using WebLogo.

Figure 7. Protein-protein network in insulin signal transduction pathway.