HYPOTHALAMIC GLUT-4 EXPRESSION - A GLUCOSE-SENSING AND INSULIN-SENSING MECHANISM

The insulin-regulatable glucose transporter, GLUT 4, is expressed prim arily in peripheral tissues (skeletal muscle and adipose tissue). In r esponse to insulin this transporter moves rapidly from an intracellula r storage site to the plasma membrane, thus accounting for the substan tial increase in glucose uptake by these tissues following insulin sti mulation. The recent finding that GLUT 4 is also expressed in the hypo thalamus suggests that this brain region, which is outside the blood-b rain barrier and therefore sensitive to circulating insulin, may exper ience stimulation of glucose uptake in response to insulin. We propose that this may allow regions of the hypothalamus to respond directly t o elevated blood glucose, constituting a form of metabolic regulation by allowing circulating glucose (and therefore insulin) in concert wit h other mechanisms to maintain blood glucose homeostasis. We consider the possible physiological role of such a mechanism and speculate that disturbances of this mechanism may occur in endocrine disease associa ted with insulin resistance.