Pp

GLUr Vesic

GLUr Vesic

Figure 1 Proposed model for the development of insulin resistance and type 2 diabetes. It is proposed that elevations in insulin levels, as a result of genetic defects and excess carbohydrate and fat intake, lead to increased levels of nonesterified fatty acids (NEFA) and hyperlipidemia. These elevated levels of lipids result in impaired (3-cell function and induce insulin resistance through changes in glucose metabolism in skeletal muscle and in the liver. These changes in metabolism in insulin responsive tissues lead to hyperglycemia and the diabetic state ensues.

Figure 1 Proposed model for the development of insulin resistance and type 2 diabetes. It is proposed that elevations in insulin levels, as a result of genetic defects and excess carbohydrate and fat intake, lead to increased levels of nonesterified fatty acids (NEFA) and hyperlipidemia. These elevated levels of lipids result in impaired (3-cell function and induce insulin resistance through changes in glucose metabolism in skeletal muscle and in the liver. These changes in metabolism in insulin responsive tissues lead to hyperglycemia and the diabetic state ensues.

as protein kinase B, also referred to as Akt, has been shown to be activated by these phosphoinositides in vitro (8,9) and in response to insulin in vivo (10) and has been proposed to be a mediator of GLUT4 translocation (11,12)

Among the proteins involved in vesicle docking and fusion with the target plasma membrane are the vesicular proteins of the synaptobrevin family and the plasma membrane proteins syntaxin4 and SNAP23 (13-17). These proteins are isoforms of functional equivalents that participate in synaptic vesicle docking and fusion with the presynaptic plasma membrane of neurons. In contrast to this knowledge, little is known about how the glucose transporter-containing vesicles sense the insulin signal or travel to the plasma membrane.

It follows that the diminished response to insulin of glucose uptake into muscle and fat could result from any of the following possibilities: defects in

Genetic Defect

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