Altered plasma insulin and glucose after obesity-producing bipiperidyl brain lesions

H. R. Berthoud and T. L. Powley A single systemic injection of bipiperidyl mustard (BPM) in the adult rat produces brain lesions and associated obesity without hyperphagia. To characterize some endocrine-metabolic aspects of the BPM preparation we measured plasma insulin and glucose dynamics as well as glucoprivic feeding. BPM-treated animals with verified lesions of the medial portion of the solitary tract nucleus (NTS) and the medial pole of the dorsal motor nucleus of the vagus (DMNX), as well as small lesions affecting the arcuate nucleus and basomedial portion of the ventromedial nucleus of the hypothalamus, showed the following characteristics: normal basal glycemia and insulinemia, exaggerated plasma insulin responses to oral or intravenous glucose and to oral saccharin, increased plasma glucose levels after oral glucose, unimpaired feeding to 2-deoxy-D-glucose challenge, decreased short-term intake of highly palatable food, and 36% more body fat at the end of the experiment. None of these changes occurred in rats that failed to develop lesions after BPM administration. These results suggest that BPM lesions (which appear to overlap distributions of central insulin binding sites) both affect a central mechanism controlling the pancreatic beta-cells and possibly influence gastric emptying and/or intestinal glucose absorption.