SYNDROME X-LIKE ALTERATIONS IN ADULT FEMALE RATS DUE TO NEONATAL INSULIN-TREATMENT

Hypothalamic structures are decisively involved in the regulation of b ody weight and metabolism. In syndrome X, complex metabolic alteration s are present, which in women are found to be associated with disturba nces of reproductive function and altered androgen levels. In previous experiments in rats, it was shown that a temporary intrahypothalamic hyperinsulinism during early life predisposes to overweight and diabet ogenic disturbances later in life, associated with disorganization of hypothalamic regulatory centers. To investigate the possible long-term consequences of elevated peripheral insulin levels during ontogenesis , the following experiment was performed, Newborn female Wistar rats w ere treated during neonatal life with daily subcutaneous injections of long-acting insulin ([IRI group] 0.3 IU on days 8 and 9 of life and 0 .1 IU on days 10 and 11 of life), whereas control animals (CO) receive d daily NaCl injections. This temporary exposure to increased insulin levels during a critical developmental period resulted in an increased body weight gain including juvenile life and adulthood (P < .01), acc ompanied by hyperinsulinemia (P < .01), impaired glucose tolerance (P < .05), and increased systolic blood pressure in adulthood (P < .025). No significant alterations were detected either in cyclicity and fert ility or in the levels of testosterone, androstenedione, or dehydroepi androsterone (DHEA) in IRI rats. Morphometric evaluation of hypothalam ic nuclei showed a reduced numerical density of neurons (P < .025) and a decreased neuronal volume density (P < .025) within the ventromedia l hypothalamic nucleus (VMN) of the IRI rats, whereas the antagonistic lateral hypothalamic area (LHA) was morphometrically unchanged. Newbo rn offspring of IRI rats (F1 generation) were overweight (P < .05) and had an increased pancreatic insulin concentration (P < .02). In concl usion, perinatal hyperinsulinism seems to predispose to the later deve lopment of syndrome X-like changes in female rats, possibly due to imp aired organization of hypothalamic regulators of body weight and metab olism. Copyright (C) 1998 by W.B. Saunders Company.