Hypothalamic GLUT 4 expression: a glucose- and insulin-sensing mechanism?

ABSTRACT

The insulin-regulatable glucose transporter, GLUT 4, is expressed primarily in peripheral tissues (skeletal muscle and adipose tissue). In response to insulin this transporter moves rapidly from an intracellular storage site to the plasma membrane, thus accounting for the substantial increase in glucose uptake by these tissues following insulin stimulation. The recent finding that GLUT 4 is also expressed in the hypothalamus suggests that this brain region, which is outside the blood-brain barrier and therefore sensitive to circulating insulin, may experience stimulation of glucose uptake in response to insulin. We propose that this may allow regions of the hypothalamus to respond directly to elevated blood glucose, constituting a form of metabolic regulation by allowing circulating glucose (and therefore insulin) in concert with 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 associated with insulin resistance.