AJP - Endocrinology and Metabolism, Vol 250, Issue 6 662-E668, Copyright © 1986 by American Physiological Society
In vivo metabolic changes as studied longitudinally after ventromedial hypothalamic lesions
L. Penicaud, F. Rohner-Jeanrenaud and B. Jeanrenaud
Ventromedial hypothalamic (VMH)-lesioned rats were tested 1 and 6 wk after
the lesions to determine, by euglycemic-hyperinsulinemic clamps, their
tissue response to insulin. One week after the lesions, total glucose
metabolism was more sensitive and responsive to insulin than in age-matched
controls. In the two groups, hepatic glucose production was suppressed at
almost identical insulin concentrations (approximately 550 microU/ml). Six
weeks after the VMH lesions, the increased insulin responsiveness of total
glucose metabolism disappeared and glucose metabolism became less insulin
sensitive (right, shifted dose-response curve) than that of control
animals. Furthermore, hepatic glucose production of VMH-lesioned rats was
now inhibited by 45% at most and at the supraphysiological insulin
concentration of 16,000 microU/ml, while it was totally suppressed by 550
microU/ml of the hormone in age-matched controls. This defect was
accompanied by a lack of decrease in plasma glucagon levels during the
clamps carried out at maximal insulin concentration. In summary, in a first
phase after VMH lesion, rats are hypersensitive and hyperresponsive to
insulin; and in a later phase, when obesity is well established,
VMH-lesioned rats become insulin resistant and are characterized by a
decreased in vivo sensitivity and responsiveness of liver and muscles to
the hormone.
