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The Hypoglycemia-Induced Rise in 1GFBP-1 Mediated by Glucocorticoids—Authors’ Response

Division of Endocrinology Children’s Hospital of Philadelphia Philadelphia, Pennsylvania 19104

We agree with Drs. Baxter and Yeoh that a rise in IGFBP-1 can occur independently of glucocorticoids. The literature supports the dominant role of insulin in the regulation of IGFBP-1. Certainly, a decline in insulin levels can result in a progressive rise in IGFBP-1 levels during fasting. We have previously demonstrated that a child with anterior pituitary insufficiency showed a rise in IGFBP-1 during fasting, although the magnitude of this rise was below the mean seen in control children (1). The data related to insulin-induced hypoglycemia is more difficult to interpret, although suppression of endogenous insulin secretion during hypoglycemia may account, in part, for the rise of IGFBP-1 that is observed. Fasting and insulin-induced hypoglycemia are different physiologic models, and thus, the factors regulating the IGFBP-1 response in these situations may not be comparable.

The above data do not preclude cortisol regulation of IGFBP-1. A recent paper suggests that IGFBP-1 is related to cortisol in human cord blood (2). The association between IGFBP-1 and cortisol that we observed throughout the entire course of fasting was statistically significant, despite the fact that cortisol levels displayed diurnal variation, while IGFBP-1 levels were steadily increasing. Thus, it is unlikely that these findings are merely coincidental. We found that the magnitude of the IGFBP-1 rise was highly variable from patient to patient, which may be related to the counterregulatory response to fasting and hypoglycemia. End-of-fast IGFBP-1 levels were strongly associated with cortisol but not with insulin, suggesting glucocorticoid regulation of IGFBP-1 during hypoinsulinemia, as has been previously demonstrated in humans (3). Under hypoinsulinemic conditions, the rise in cortisol in response to fasting and acute hypoglycemia may augment the rise in IGFBP-1, which occurs with the reduction of insulin secretion.

In adrenalectomized rats, the IGFBP-1 rise to insulin-induced hypoglycemia was found to be blunted, leading Lewitt et al. (4) to postulate the involvement of an adrenal factor. While our data support the role of cortisol in the regulation of IGFBP-1 levels during fasting hypoglycemia, the control of IGFBP-1 secretion is not yet fully defined. It is likely that additional regulators (possibly an as yet unidentified adrenal factor) together with insulin and cortisol also participate in the control of IGFBP-1 during fasting and hypoglycemia. Characterizing the regulators of IGFBP-1 secretion will further illuminate the role of this protein in the modulation of blood glucose levels.

Footnotes

Received March 22, 1999. Address correspondence to: Lorraine Levitt Katz, Division of Endocrinology, Children’s Hospital of Philadelphia, 34th Street & Civic Center Boulevard, Philadelphia, Pennsylvania 19104.

References

1. Katz LEL, Satin-Smith MS, Collett-Solberg P, et al. 1997 Insulin-like growth factor binding protein-1 levels in the diagnosis of hypoglycemia due to hyperinsulinism. J Pediatr. 131:193–199.[CrossRef][Medline]
2. Cianfarani S, Germani D, Rossi L, et al. 1998 IGF-I and IGF binding protein-1 are related to cortisol in human cord blood. Eur J Endocrinol. 138:524–529.[Abstract]
3. Conover C, Divertie GD, Lee PD. 1993 Cortisol increases plasma insulin-like growth factor binding protein-1 in humans. Acta Endocrinol. 128:140–143.
4. Lewitt MS, Saunders H, Baxter RC. 1992 Regulation of rat insulin-like growth factor binding protein-1: the effect of insulin induced hypoglycemia. Endocrinology. 131:2357–2364.[Abstract/Free Full Text]

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