Investigation of the Effect of Insulin upon Regional Brain Glucose Metabolism in the Rat in Vivo*

Abstract

The hypothesis that insulin might promote increased glucose metabolism in putative glucoreceptor areas of the brain was investigated in the rat. Using tritiated 2-deoxyglucose (2-DG), unanesthetized fasted rats were injected with 0.1 U insulin and studied 30 min later. The local uptake of 2-DG into discrete brain areas was examined in serial frozen 400-μm sections. Areas 1.1 mm in diameter were punched from the region of the ventral medial, ventral lateral, and dorsal hypothalamus and from a control area from the cerebral cortex. The punched tissue segments were analyzed for total radioactivity and protein content. The results showed that insulin failed to influence the pattern of 2-DG uptake into these discrete brain regions. When the data were analyzed with a simple kinetic model to determine the net fractional rate of uptake of 2-DG by the tissues, brain tissues displayed a 75% rate increase compared to saline-treated controls. Heart muscle collected from the same rats showed a 700% increase after insulin, while lung, an insulin insensitive tissue, displayed a 30% increase. Because the nonsteady state conditions of the model dictate a number of assumptions, the modest increase in the calculated rate of uptake in brain tissue must be verified by a steady state model before it can be accepted as representing a real effect of insulin upon the overall metabolism of glucose in the brain. Regardless of these reservations, it may be concluded from the pattern of response, that insulin does not selectively increase glucose uptake or metabolism in the putative glucoreceptor areas of the hypothalamus under the conditions of these experiments.