INJECTION WITH GOLD THIOGLUCOSE IMPAIRS SENSITIVITY TO GLUCOSE - EVIDENCE THAT GLUCOSE-RESPONSIVE NEURONS ARE IMPORTANT FOR LONG-TERM REGULATION OF BODY-WEIGHT

It has been proposed, but never demonstrated, that glucose-responsive neurons are essential for the long-term regulation af body weight, and that mice injected with gold-thio-glucose (GTG) become obese due to d estruction of glucose-responsive neurons. To assess these hypotheses, mice were injected with either saline (control) or a dose of GTG that produces obesity, and the effects on feeding of peripheral injection o f saline, glucose, 2-deoxyglucose (2-DG), or cholecystokinin (CCK) wer e measured. In control mice, 2-DG increased, whereas glucose and CCK d ecreased, food intake significantly. In contrast, in GTG-treated mice, 2-DG and glucose did not have a significant effect on food intake. Th e GTG-treated mice remained sensitive to the inhibitory effect of CCK on food intake. These data indicate that i.p. injection of GTG, which produces obesity, also destroys glucose-responsive neurons, consistent with the hypothesis that glucose-responsive neurons contribute to the long-term regulation of body weight.