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-micrometer 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.

The Effects of Differing Insulin Levels on the Hormonal and Metabolic Response to Equivalent Hypoglycemia in Normal Humans

“…We speculate that our results are most likely explained by a direct action on the brain by the higher insulin levels. This is a contentious issue with data both for and against such a construct (1,(38)(39)(40). However, in vivo data from the conscious dog strongly indicate that the brain directs the counterregulatory response (41), and increased insulin levels in the brain circulation can augment the catecholamine and cortisol hormone response to hypoglycemia (42).…”

Hyperinsulinemia Suppresses Glucose Utilization in Specific Brain Regions:In VivoStudies Using the Euglycemic Clamp in the Rat

“…One implicit assumption in studies performed during nonsteady state conditions (9,10,12) is the constancy, with the degree of glycemia, of the LC, a term describing the relative rates of phosphorylation of 2DG and glucose. However it has been shown that the LC increases markedly during hypoglycemia (31), an effect that makes it difficult to interpret results obtained during nonsteady state conditions (9,10,12). Only two studies (11,12) have reported results obtained during steady state conditions for glucose.…”

“…However, the effect of insulin on these parameters has been the subject of conflicting reports (7)(8)(9)(10)(11)(12). Difficulties of interpretation (8)(9)(10) have resulted largely from the lack of the major requirements of tracer study of blood-brain substrate transfer, namely the lack of metabolic steady state conditions and/or unidirectional transport (13). The aim of the present study was to examine whether insulin alters brain glucose metabolism independently of changes in blood glucose.…”

Insulin Response in Individual Tissues of Control and Gold Thioglucose-Obese Mice In Vivo With [1-14C]2-Deoxyglucose

“…Recently, however, methods have been developed for examining the insulin response of several tissues from one animal in vivo with the uptake and metabolism of the glucose analogue 2-deoxyglucose (2-DG) as a relative index of glucose metabolism (8,9). This in vivo method under steady-state (10) and non-steady-state (12) conditions has demonstrated the heterogeneity of tissue responses to insulin.…”