The effect of acute and chronic insulin administration on insulin-like growth factor-I expression in the pituitary-intact and hypophysectomised rat

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Abstract
Although growth hormone is known to be the main regulator of insulin-like growth factor-I, insulin has also been shown to play a role in regulating serum insulin-like growth factor I levels in diabetic animals. While this effect is thought to be due to correction of metabolic perturbations, some studies have suggest that insulin may have a direct effect on growth and/or insulin-like growth factor-I levels. We have examined the effects of acute and chronic insulin administration to non-diabetic, pituitary-intact and hypophysectomised rats. Rats were injected intraperitoneally with insulin as an acute bolus (10 U) or a chronic subcutanious infusion (low dose; 2.4 U/day, high dose; 12 U/day) over 5 days. Insulin-like growth factor-I mRNA was quantitated by Northern and slot blots of RNA from various tissues. A small (less than 2-fold) but significant increase (pp<0.05) in serum insulin-like growth factor-I levels was also observed 6 h after insulin injection. In contrast, in pituitary-intact rats which received high dose insulin infusion and were hypoglycaemic at the time of death, tissue levels of insulin-like growth factor-I mRNA were reduced compared to saline-treated control groups. Similarly in the hypophysectomised rats neither acute nor chronic insulin administration had any consistent effect on insulin-like growth factor-I mRNA abundance in any of the tissues examined. This data suggests that insulin has no direct effect in regulating insulin-like growth factor-I gene expression. The small effects demonstrable in pituitary-intact rats may result from a synergistic action of insulin with growth hormone or other pituitary factors.