An insulin-like modular basis for the evolution of glucose transporters (GLUT) with implications for diabetes.

ABSTRACT: Glucose transporters (GLUT) are twelve-transmembrane spanning proteins that contain two pores capable of transporting glucose and dehydroascorbate in and out of cells. The mechanism by which transport is effected is unknown. An evolutionarily-based hypothesis for the mechanism of glucose transport is presented here based on reports that insulin has multiple binding sites for glucose. It is proposed that insulin-like peptides were incorporated as modular elements into transmembrane proteins during evolution, resulting in glucose transporting capacity. Homology searching reveals that all GLUT contain multiple copies of insulin-like regions. These regions map onto a model of GLUT in positions that define the glucose transport cores. This observation provides a mechanism for glucose transport involving the diffusion of glucose from one insulin-like glucose-binding region to another. It also suggests a mechanism by which glucose disregulation may occur in both type 1 and type 2 diabetes: insulin rapidly self-glycates under hyperglycemic conditions. Insulin-like regions of GLUT may also self-glycate rapidly, thereby interfering with transport of glucose into cells and disabling GLUT sensing of blood glucose levels. All aspects of the hypothesis are experimentally testable.

SUBMITTER: Root-Bernstein R 

PROVIDER: S-EPMC2674801 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature