Increased Jejunal Absorption of Glucose in Rats Submitted to Blockade of GABAA Receptors in the Hypothalamic Paraventricular Nucleus

ABSTRACT

In this study we investigated the status of jejunal absorption and peripheral metabolism of glucose following disinhibition of paraventricular nucleus (PVN) induced by the GABA_A antagonist bicuculline methiodide (BMI). Adult male Wistar rats (270-300g) were anesthetized to implant unilateral guide cannula targeted to PVN for later microinjection of BMI (10 pmol/100 nl, n=6) or vehicle (NaCl 0.9 % /100 nl, n=5). The jejunal loop was isolated and perfused (0.5 mL/min) with Tyrode solution containing twice the normal concentrations of glucose, sodium, and potassium. After microinjections into PVN, perfusate and blood samples were taken every 10 min over a 40 min period. In comparison with vehicle, BMI into PVN increased glucose absorption at 30 min (1.2 ± 0.1 vs. 1.8 ± 0.1 µmol/min; *P<0.05) and at 40 min (1.3 ± 0.2 vs. 2.4 ± 0.3 µmol/min; *P<0.05), whereas plasma insulin was significantly reduced (0.5 ± 0.04 vs. 0.3 ± 0.04 ng/ml, *P<0.01). At the end of the experiment, samples from the liver and gastrocnemius muscle were taken to measure levels of glycogen, intermediate metabolites of the glycolytic pathway and ATP. Compared to control, muscle glucose-6- phosphate (0.380 ± 0.063 vs. 0.253 ± 0.020 µmol/g; P<0.05) and ATP (0.166 ± 0.065 vs. 0.038 ± 0.013 µmol/g; *P<0.05) were reduced in the group microinjected with BMI into PVN. We conclude that PVN disinhibition changes the absorption and peripheral glucose metabolism.

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