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An Insulin-Like Modular Basis for the Evolution of Glucose Transporters (GLUT) with Implications for Diabetes
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 i...
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Formato: | Texto |
Lenguaje: | English |
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Libertas Academica
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674801/ https://www.ncbi.nlm.nih.gov/pubmed/19430606 |
Sumario: | 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. |
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