Ventromedial hypothalamic lesions in rats suppress counterregulatory responses to hypoglycemia

The central nervous system has been implicated in the activation of counterregulatory hormone release during hypoglycemia. However, the precise loci involved are not established. To determine the role of the ventromedial hypoglycemia, we performed hypoglycemic clamp studies in conscious Sprague-Dawl...

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Bibliographic Details
Published in:The Journal of clinical investigation 1994-04, Vol.93 (4), p.1677-1682
Main Authors: BORG, W. P, DURING, M. J, SHERWIN, R. S, BORG, M. A, BRINES, M. L, SHULMAN, G. I
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carbohydrates
Epinephrine - blood
Fundamental and applied biological sciences. Psychology
Glucagon - blood
Hormones - blood
Hypoglycemia - blood
Insulin - blood
Male
Metabolisms and neurohumoral controls
Norepinephrine - blood
Rats
Rats, Sprague-Dawley
Ventromedial Hypothalamic Nucleus - physiology
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary:The central nervous system has been implicated in the activation of counterregulatory hormone release during hypoglycemia. However, the precise loci involved are not established. To determine the role of the ventromedial hypoglycemia, we performed hypoglycemic clamp studies in conscious Sprague-Dawley rats with bilateral VMH lesions produced by local ibotenic acid injection 2 wk earlier. Rats with lesions in the lateral hypothalamic area, frontal lobe, sham operated (stereotaxic needle placement into hypothalamus without injection), and naive animals served as control groups. The clamp study had two phases. For the first hour plasma glucose was fixed by a variable glucose infusion at euglycemia (approximately 5.9 mM). Thereafter, for an additional 90 min, glucose was either allowed to fall to (a) mild hypoglycemia (approximately 3.0 mM) or (b) more severe hypoglycemia (approximately 2.5 mM). Glucagon and catecholamine responses of lateral hypothalamic area-, frontal lobe-lesioned, sham operated, and naive animals were virtually identical at each hypoglycemic plateau. In contrast, glucagon, epinephrine, and norepinephrine responses in the VMH-lesioned rats were markedly inhibited; hormones were diminished by 50-60% during mild and by 75-80% during severe hypoglycemia as compared with the other groups. We conclude that the VMH plays a crucial role in triggering the release of glucagon and catecholamines during hypoglycemia.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI117150