Evidence for sexual differences in the preoptic area regulation of blood glucose in rats

Abstract

The effect of noradrenaline (NA) injection (20 or 40 nmol) into the preoptic area (POA) on plasma glucose and insulin was studied in male and female rats. The rats were implanted with chronic jugular catheters for blood sampling and unilateral intracerebral cannulas placed just above the POA. Blood samples were taken before and at 5, 10, 15, 30 and 60 min after NA injection. As early as 5 min after NA injection, plasma glucose levels rose rapidly in both male and female rats, reaching a peak at 15 min poststimulus. NA injection into the POA caused a dose-dependent hyperglycemic response in both male and female rats, although the response was more intense and longer lasting in females than in males. However, NA injection into the POA induced an increase in plasma insulin concentration in male but not in female rats. In addition, the increase in plasma glucose induced by 40 nmol NA injection in males preceded that of insulin. Plasma levels of glucose after POA injection of NA were already significantly elevated (p<0.01) within the first experimental interval (5 min), whereas a plasma insulin increase were first detected 15 min post injection. We conclude that, when administered locally into the POA, NA can activate the sympathetic outflow expressed by a neurally mediated hyperglycemia which is more intense in females than in males. These data demonstrate that the POA has a sexually differentiated function in the regulation of glycemia.

Introduction

The preoptic area (POA) is a major integrative area for the maintenance of internal homeostasis 8, 23, 24, 30. In previous studies from this laboratory we obtained evidence for the existence of a center in the rat POA that can influence glycemia and free fatty acid mobilization probably by activating sympathetic fibers of adipose tissue. The POA control of glycemia and lipolysis can be activated in situations that require rapid mobilization of metabolic reserves, such as exposure to cold 6, 18and neuroglucopenia 4, 5. Although an increased release of noradrenaline (NA) into the POA has been shown to occur during neurocytoglucopenia [19], there are no experimental data showing that a direct stimulation of the adrenergic neurons in the POA can interfere with hepatic glucose production or induce a change in plasma glucose levels. On the other hand, the demonstration that dramatic alterations in the brain structure accompany sexual differentiation 11, 17suggests that new insights into the possible mechanisms of the neural control of blood glucose will be forthcoming. The functional significance of this morphological sex difference of the POA is still unclear. There is also electrophysiological evidence for sexual dimorphism [31]and studies on POA lesions have shown differences in hormone response [13]. In order to study the influence of POA noradrenergic afferents on plasma glucose levels and to determine whether sexual differences in the regulation of glycemia exist, we investigated the effect of NA injection into the POA of conscious and unrestrained male and female rats.