Patients afflicted with diabetes are at risk for a variety of pathologies resulting in many complications including foot ulceration and amputation. The multi-factorial etiology of diabetic foot ulcers is evidenced by the numerous pathophysiologic pathways that can potentially lead to this disorder. A multicenter study attributed 63 percent of diabetic foot ulcers to the critical triad of peripheral sensory neuropathy, deformity, and trauma (Reiber, et al., 1999). The following discusses the pathophysiology of each of the triad in limited detail.
Background: Glucose is liberated from dietary carbohydrate such as starch or sucrose by hydrolysis within the small intestine, and absorbed into the blood. GLUT-2 transporters carry glucose in to beta cells via insulin-independent facilitated diffusion. Through rapid glycolysis, intracellular glucose is immediately phosphorylated and therefore, cannot diffuse out (the transport protein is specific for glucose). Internal glucose (unphosphorylated) concentration remains low providing a large concentration gradient for entry into the cell. Aerobic metabolism leads to increased ATP/ADP ratios and ATP sensitive K+ channels close. Depolarization activates voltage gated Ca2+ channels and insulin exocytosis. Insulin binds to the insulin receptor and activates a tyrosine kinase second messenger system. Auto phosphorylation of the insulin receptor causes insulin-dependent GLUT transporters to be inserted into the cell membranes of insulin dependent cells like muscle cells. Glucose uptake and utilization promotes the use of glucose and the lowering of blood glucose levels.
Elevated concentrations of glucose in the blood stimulates release of insulin which stimulates increase in number of GLUT transporters at the membrane surface. This in turn increases the diffusion rate while the driving force (phosphorylation) remains the same. Low insulin levels, as in diabetes, decrease the number of glucose transporters at membrane...
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