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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 12 4426-4430
Copyright © 1998 by The Endocrine Society

From the Clinical Research Centers

Dual Regulation of Insulin-Like Growth Factor Binding Protein-1 Levels by Insulin and Cortisol during Fasting1

Lorraine E. Levitt Katz, M.D,, Marta S. Satin-Smith, Paulo Collett-Solberg, Lester Baker, Charles A. Stanley and Pinchas Cohen, M.D.

Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Address all correspondence to Lorraine Katz, M.D., Assistant Professor of Pediatrics, Children’s Hospital of Philadelphia, Division of Endocrinology, 34th Street and Civic Center Boulevard, Philadelphia, Pennsylvania 19104. E-mail: katzl{at}email.chop.edu


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) gene transcription is known to be inhibited by insulin in vivo and in vitro. Levels of IGFBP-1 typically rise during fasting but also rise after acute hypoglycemia, including that induced by insulin, through an unknown mechanism that may involve counterregulatory hormones such as cortisol. To study the regulation of IGFBP-1 secretion during fasting, we measured IGFBP-1, insulin, cortisol, GH, and glucose during the course of standardized fasting studies in a total of 21 children. The fasting studies lasted 13–32 h and were terminated for a whole-blood glucose concentration of less than 50 mg/dL (2.8 mmol). Of the children studied, 9 children had no disorder, 8 had ketotic hypoglycemia, 2 had isolated GH deficiency, and 2 had fatty acid oxidation disorders. During fasting, IGFBP-1 rose above the mean baseline levels of 28 ± 5 ng/mL to a mean level ± SEM of 336 ± 59 ng/mL at the time of hypoglycemia (P = 0.001). IGFBP-1 was strongly associated with serum insulin and cortisol levels over the entire course of fasting (P < 0.0001)). The interaction of the 2 hormones across time was also strongly significant (P < 0.0001). There was no statistically significant association between IGFBP-1 and GH or glucose. At the time of hypoglycemia, insulin levels were suppressed to 1.7 µU/mL or less, and there was no correlation between IGFBP-1 levels at the end of fasting and final insulin level. In contrast, cortisol levels correlated with IGFBP-1 in the final hypoglycemic sample (r = 0.56, P < 0.01). Partial correlation analysis revealed that the relationship between IGFBP-1 and cortisol was unchanged when the data was controlled for insulin levels. These data show that insulin and cortisol both regulate IGFBP-1 secretion during fasting; the effects of insulin and cortisol are strong during the course of fasting. Significant hypoglycemia stimulates a further rise in IGFBP-1, which seems to be regulated, in part, by cortisol. The cortisol-induced rise in IGFBP-1 during fasting and during hypoglycemia potentially serves to prevent the hypoglycemic effects of free IGFs.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
INSULIN-LIKE growth factor (IGF) binding protein-1 (IGFBP-1) is a 28-kDa protein that is produced by liver and decidua and is found mainly in serum and amniotic fluid. It binds the IGFs with high affinity and is able to either inhibit or enhance IGF action in vitro (1, 2, 3). Its secretion by the liver into serum is acutely suppressed by insulin, and that the inhibitory effects of insulin are mediated at the level of transcription (4, 5). IGFBP-1 levels typically rise during fasting and exercise and are increased in poorly controlled insulin-dependent diabetes mellitus, reflecting deficiency of insulin (6, 7, 8, 9, 10, 11). Under conditions associated with elevated insulin levels (including postprandial states, hyperinsulinemic clamps, and insulinomas), decreased IGFBP-1 levels are seen (11, 12). The inverse relationship between IGFBP-1 and insulin is maintained diurnally, in relation to meals, with IGFBP-1 being the only IGFBP whose serum levels fluctuate 10- to 20-fold during the course of a day (13). It has been hypothesized that IGFBP-1 serves to block the potential hypoglycemic actions of the IGFs (1, 2) and, therefore, is secreted at times of hypoglycemia, such as fasting.

It has also been reported that hypoglycemia, including that induced by insulin, stimulates a rise in IGFBP-1 levels 1–2 h after the glycemic nadir, in a pattern which resembles glucose counterregulatory hormones (14, 15, 16). Though this phenomenon is not well understood, it has been suggested that adrenal factors may be involved (16). At the molecular level, it has been demonstrated that IGFBP-1 gene transcription is inhibited by insulin via an insulin responsive element and is stimulated by cortisol via a cortisol-responsive element (17, 18). The rise in IGFBP-1 may serve to inhibit the metabolic actions of IGF-I during acute hypoglycemia, supporting a role for IGFBP-1 in glucose counterregulation (3). To study the regulation of IGFBP-1 during fasting, leading to hypoglycemia in children, we measured IGFBP-1 levels in combination with insulin and cortisol during the course of standardized fasting studies in children admitted to the Generalized Clinical Research Center.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Study design

The patient population consisted of 21 children (age, 1–7 yr) with known or suspected hypoglycemic disorders. Two of these children had previously been demonstrated to have isolated GH deficiency, by provocative testing, with an intact cortisol response to cortrosyn. Additionally, 3 patients who were undergoing fasts for a ketogenic diet protocol were studied. After the families gave informed consent, standardized fasting studies were conducted in the Clinical Research Center at Children’s Hospital of Philadelphia under an Institutional Review Board-approved protocol. A total of 21 patients were studied. The fasting studies lasted 13–32 h and were terminated for a whole-blood glucose concentration of less than 50 mg/dL (2.8 mmol). Children who were not able to fast for 24 h, but whose hormonal response to fasting was normal, in combination with appropriate generation of ketones and free fatty acids, were diagnosed with ketotic hypoglycemia. Patients with normal metabolic and hormonal profiles who became hypoglycemic after 24 h of fasting were considered to have no disorder. Of the total 21 patients studied, 9 were determined to have no disorder, 8 had ketotic hypoglycemia, 2 had isolated GH deficiency, and 2 had fatty acid oxidation disorders. Details of the patients are provided in Table 1Go. At regular intervals during the fasting and at the time of hypoglycemia, blood samples were drawn for IGFBP-1, insulin, GH, and cortisol. After the final blood draw, patients then were given either oral carbohydrate or iv glucose and were observed until they were back on a full oral diet and had stable blood glucose levels.


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  		Table 1. Population characteristics

 
Methods

IGFBP-1 levels were measured at Nichols Institute Diagnostics (San Juan Capistrano, CA) by a double-antibody RIA using rabbit anti-IGFBP-1 and 125IGFBP-1. The assay sensitivity was 0.4 ng/mL at 90% B/Bo. Insulin was measured by the IMx0 insulin microparticle immunoassay (Abbott Laboratories, Abbot Park, IL). This assay had a sensitivity <=1.0 µU/mL, with an intraassay variation of 3.1% and an interassay variation of 3.8%. Left censored data were assigned the value of 1 for the study analysis.

Cortisol was measured by the TDxFLx Fluorescence Polarization Immunoassay method (Abbott Laboratories). This assay has a sensitivity of 0.64 µg/dL.

GH was measured by the DELFIA fluoroimmunometric assay (Wallac, Inc. Turku, Finland). The sensitivity of this assay is 0.03 mU/L.

Statistical analysis. Measurements of IGFBP-1, insulin, cortisol, glucose, and GH were taken at different time points after the start of fasting condition. The effects of insulin, cortisol, glucose, and GH on IGFBP-1 across time were analyzed based on a longitudinal mixed-effects approach. This model extends the usual repeated-measures approach in ANOVA by enabling us to associate linearly the repeated-outcome variable with a continuous explanatory variable, such as time of measurement, and to include in the analysis all observed subjects, even when some subjects do not have a complete set of measurements. The BMDP5V statistical package was used for the analyses (19). Models were fit to IGFBP-1, to each of four potential predictors (insulin, cortisol, glucose, and GH) separately, to test for effects over time. Natural logarithm values were used. Time was measured as: time since the start of the fasting condition. Models explaining prospective relationships between changes in IGFBP and changes in the other parameters (insulin, cortisol, glucose, and GH) were fit. Those parameters with statistically significant main effects were included together in a full model, allowing for interaction terms.

Spearman correlation was performed to analyze the relationships between IGFBP-1 levels and several fasting parameters in the final hypoglycemic sample.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
IGFBP-1 levels rose during fasting, from mean (±SE) baseline levels of 28 ± 5 ng/mL to a mean level ± SEM of 336 ± 59 ng/mL at the time of hypoglycemia, which occurred after 13–32 h in all of the children studied. The rise in IGFBP-1 was statistically significant by paired t test (P = 0.001). However, there was no direct correlation between peak IGFBP-1 levels at the end of fasting and total length of fast. IGFBP-1 levels rose over time and were elevated in the final blood sample in all of the children studied. There were no significant differences between patients in the different diagnostic categories, with regard to their IGFBP-1 rise or hormonal variations during fasting. Over the course of fasting, mean insulin and C-peptide levels steadily declined, and cortisol levels varied according to a diurnal pattern. At the point of hypoglycemia, cortisol levels demonstrated a rise above baseline values at the start of fasting, to a mean of 22 ± 2.3 µg/dL. GH levels were highly variable and did not demonstrate a mean interval rise at the time of hypoglycemia. Table 2Go presents the select hormonal parameters at the time of hypoglycemia for the entire group.


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  		Table 2. Serum hormone levels at the time of hypoglycemia

 
The relationships between IGFBP-1 (across time) and insulin, cortisol, glucose, and GH are presented in Table 3Go. IGFBP-1 was strongly associated with serum insulin and cortisol levels over the entire course of fasting [Table 3Go (models 1 and 2), Figs. 1Go and 2Go]. There was no statistically significant association between IGFBP-1 and GH or glucose (Table 3Go, models 3 and 4). When the model was fit to IGFBP-1 with both insulin and cortisol as predictors, the effect of insulin drops out (P = 0.2734), whereas the effect of cortisol remains strong (P = 0.0000) (Table 3Go, model 5). Furthermore, when the model was fit to IGFBP-1 and the insulin/cortisol interaction, the interaction of the two hormones is statistically significant (Table 3Go, model 6).


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  		Table 3. Associations between IGFBP-1, hormonal parameters, and glucose during fasting

 


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  		Figure 1. Relationships between levels of IGFBP-1 and insulin, over the course of fasting. Closed triangles, ln(IGFBP-1) Rsq = 0.4486; closed circles, ln(insulin+1) Rsq = 0.3609.

 


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  		Figure 2. Relationships between levels of IGFBP-1 and cortisol, over the course of fasting. Closed triangles, ln(IGFBP-1) Rsq = 0.4486; closed squares, ln(cortisol) Rsq = 0.2055.

 
Correlation analysis of the final hypoglycemic sample is shown in Fig. 3Go. At the time of hypoglycemia, when insulin levels were suppressed to measure <=1.7 µU/mL, there was no direct correlation between peak IGFBP-1 levels at the end of fasting and final insulin level. In contrast to insulin, cortisol levels strongly correlated with IGFBP-1 in the final hypoglycemic sample (r = 0.56, P < 0.01) (Fig. 3Go). At the time of hypoglycemia, there was no correlation between glucose level with IGFBP-1 or with cortisol. Partial correlation analysis revealed that the relationship between IGFBP-1 and cortisol was unchanged when the data were controlled for insulin levels, indicating that the correlation of IGFBP-1, as a function of cortisol, was independent of its relationship to insulin.



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  		Figure 3. Relationship between plasma IGFBP-1 and cortisol at the time of hypoglycemia. The correlation between the two parameters is r = 0.56, P < 0.01 (y = 1033.448 · 100.018x).

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
It has previously been demonstrated that IGFBP-1 levels rise during fasting (6, 7), but most of the studies performed were not carried out to the point of hypoglycemia. Furthermore, before the present study, there was little data correlating IGFBP-1 levels with fasting parameters other than insulin and glucose. We have confirmed that IGFBP-1 levels rise with fasting and are elevated in the final blood sample of patients at the time of hypoglycemia, regardless of the etiology of hypoglycemia.

In all of the conditions that have been studied, IGFBP-1 levels are inversely correlated with plasma insulin levels (10, 11, 12, 20). Given the exquisite sensitivity of IGFBP-1 to insulin, it has remained a paradox that IGFBP-1 levels rise acutely in response to insulin-induced hypoglycemia. Some have postulated that glucose, not insulin, regulates IGFBP-1 during fasting and hypoglycemia. Other investigators postulated that suppression of insulin secretion into the hepatic portal circulation, as a result of hypoglycemia, may account for the acute rise in IGFBP-1 levels (21). Our data would suggest that during fasting hypoglycemia, a state of low endogenous insulin secretion, other factors (particularly cortisol) may play a role in the stimulation of IGFBP-1 secretion, as previously suggested by Lewitt et al. (16).

In vitro data have demonstrated a stimulatory role for glucocorticoids on IGFBP-1 gene transcription and IGFBP-1 secretion by liver cells ((17, 18, 22, 23, 24). In rat H4IIe hepatoma cells, insulin and glucocorticoids were shown to have opposite effects on IGFBP-1 secretion, with the effects of insulin dominating (25). In animals, the administration of glucocorticoids has been shown to increase IGFBP-1 (26, 27). The latter study examined the effects of glucocorticoid administration on adrenal intact and adrenalectomized diabetic rats. The diabetic animals demonstrated elevated IGFBP-1 levels, as would be predicted, because of their insulin deficiency; these effects were prevented by adrenalectomy, and restored by glucocorticoid administration, supporting a role for glucocorticoids on IGFBP-1 secretion in insulin-deficient states. The one human study that examined this phenomenon demonstrated that, under a hypoinsulinemic state induced by SRIF, an infusion of cortisol increased IGFBP-1 levels beyond the increase induced by hypoinsulinemia alone (28). Together, these studies support a role for IGFBP-1 in glucose counterregulation, and they suggest that glucocorticoid stimulation of IGFBP-1 predominates during low-insulin states.

One of the postulated roles of IGFBPs is the prevention of the potential hypoglycemia that could arise from high plasma levels of free IGFs (1, 2, 3). IGFBP-1 is thought to be the primary IGF binding protein involved in the acute regulation of serum glucose levels (29). The elevated IGFBP-1 levels seen in poorly controlled diabetes mellitus may contribute to hyperglycemia by the binding endogenous IGF-I and preventing its insulin-like effects (9). Conversely, the elevated IGFBP-1 levels seen under fasting conditions may prevent hypoglycemia in normal individuals by the same mechanism. During acute hypoglycemia, the rise in IGFBP-1 may also serve to inhibit the metabolic actions of IGF-I.

Our data, during fasting hypoglycemia, show that IGFBP-1 secretion is regulated by cortisol together with insulin. The effects of insulin and cortisol are both strong during the course of fasting. The development of significant hypoglycemia stimulates a rise in IGFBP-1 that is associated with serum cortisol concentration. A model of IGFBP-1 regulation is depicted in Fig. 4Go. The rise in IGFBP-1, during fasting and hypoglycemia, may be regulated, in part, by cortisol; and this potentially serves to prevent the additional hypoglycemic effects of free IGFs.



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  		Figure 4. Hypothetical model of IGFBP-1 regulation during nonfasting (A) and fasting states (B).

 


   Footnotes
 
1 Supported, in part, by NIH Grant GCRC-MO1-RR-00240, an NIH CAP Award (to L.K.), an NIH Child Health Research Center Award (to L.K.), and FDA Grant FD-R-001181–01 (to P.C.). Back

Presented, in part, at the 1996 International Congress of Endocrinology, San Francisco, California.

Received July 31, 1997.

Revised January 29, 1998.

Accepted September 2, 1998.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Katz LEL, Cohen P, Rosenfeld R. 1995 Clinical significance of IGF binding proteins. Endocrinologist. 5:36–43.
  2. Cohen P, Fielder P, Hasegawa Y, Frisch H, Guidice LC, Rosenfeld RG. 1991 Clinical aspects of insulin-like growth factor binding proteins. Acta Endocrinol (Copenh). 124:74–85.
  3. Lee PDK, Conover CA, Powell DR. 1993 Minireview. Regulation and function of insulin-like growth factor-binding protein-1. Proc Soc Exp Biol Med. 204:4–29.[CrossRef][Medline]
  4. Ooi GT, Tseng LY, Tran MQ, Rechler MM. 1992 Insulin rapidly decreases insulin-like growth factor binding protein-1 gene transcription in streptozotocin-diabetic rats. Mol Endocrinol. 6:2219–2228.[Abstract/Free Full Text]
  5. Powell DR, Suwanichkul A, Cubbage ML, DePaolis LA. 1991 Insulin inhibits transcription of the human gene for insulin-like growth factor binding protein-1. J Biol Chem. 266:18868–18876.[Abstract/Free Full Text]
  6. Cotterill AM, Holly JM, Wass JA. 1993 The regulation of insulin-like growth factor binding protein (IGFBP)-1 during prolonged fasting. Clin Endocrinol (Oxf). 39:357–362.[Medline]
  7. Busby WH, Snyder DK, Clemmons DR. 1988 Radioimmunoassay of a 26,000-dalton plasma insulin-like growth factor binding protein: control by nutritional variables. J Clin Endocrinol Metab. 67:1225–1230.[Abstract/Free Full Text]
  8. Suikkari AM, Sane T, Seppälä M, Yki-Järvinen H, Karonen SL, Koivisto VA. 1989 Prolonged exercise increases serum insulin-like growth factor concentrations. J Clin Endocrinol Metab. 68:141–144.[Abstract/Free Full Text]
  9. Batch JA, Baxter RC, Werther G. 1991 Abnormal regulation of IGFBPs in adolescents with IDDM. J Clin Endocrinol Metab. 73:964–968.[Abstract/Free Full Text]
  10. Brismar K, Gutniak M, Povoa G, Werner S, Hall K. 1988 Insulin regulates the 35 kDa IGF binding protein in patients with diabetes mellitus. J Endocrinol Invest. 11:599–602.[Medline]
  11. Suikkari AM, Koivisto VA, Rutanen EM, Yki-Järvinen H, Karonen SL, Seppälä M. 1988 Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein. J Clin Endocrinol Metab. 66:266–272.[Abstract/Free Full Text]
  12. Katz LEL, Satin-Smith MS, Collett-Solberg P, et al. 1997 Insulin-like growth factor binding protein-1 levels in the diagnosis of hypoglycemia caused by hyperinsulinism. J Pediatr. 131:193–199.[CrossRef][Medline]
  13. Baxter RC, Cowell CT. 1987 Diurnal rhythm of growth hormone independent binding protein for insulin-like growth factors in human plasma. J Clin Endocrinol Metab. 65:432–440.[Abstract/Free Full Text]
  14. Cotterill AM, Cowell CT, Baxter RC, McNeill D, Silinik M. 1988 Regulation of growth hormone-independent growth factor-binding protein in children. J Clin Endocrinol Metab. 67:882–887.[Abstract/Free Full Text]
  15. Yeoh SI, Baxter RC. 1988 Metabolic regulation of the growth hormone independent insulin-like growth factor binding protein in human plasma. Acta Endocrinol (Copenh). 119:465–473.[Abstract/Free Full Text]
  16. 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]
  17. Suh DS, Ooi GT, Rechler MM. 1994 Identification of cis-elements mediating the stimulation of the rat insulin-like growth factor-binding protein-1 promoter activity by dexamethasone, cyclic adenosine 3'5' monophosphate, and phorbol esters, and inhibition by insulin. Mol Endocrinol. 8:794–805.[Abstract/Free Full Text]
  18. Goswami R, Lacson R, Yang E, Sam R, Unterman T. 1994 Functional analysis of glucocorticoid, and insulin response sequences in the rat insulin-like growth factor-binding protein-1 promoter. Endocrinology. 134:736–743.[Abstract/Free Full Text]
  19. Dixon WJ, ed. 1992 BMDP statistical software manual, vol 2. Los Angeles, CA: University of California Press.
  20. Snyder DK, Clemmons DR. 1990 Insulin-dependent regulation of insulin-like growth factor-binding protein-1. J Clin Endocrinol Metab. 71:1632–1636.[Abstract/Free Full Text]
  21. Cotterill AM, Holly JMP, Amiel S, Wass JA. 1993 Suppression of endogenous insulin secretion regulates the rapid rise of insulin-like growth factor binding protein-1 levels following acute hypoglycemia. Clin Endocrinol (Oxf). 38:633–639.[Medline]
  22. Orlowski CC, Ooi GT, Rechler MM. 1990 Dexamethasone stimulates transcription of the insulin-like growth factor binding protein-1 gene gene expression in H4-II-E rat hepatoma cells. Mol Endocrinol. 4:1592–1599.[Abstract/Free Full Text]
  23. Powell D, Lee PD, DePaolis LA, Morris SL, Suwanichkul A. 1993 Dexamethasone stimulates expression of insulin-like growth factor binding protein-1 in HEP G2 human hepatoma cells. Growth Regul. 3:11–13.[Medline]
  24. Miura Y, Higashi Y, Kato H, Takahashi S, Nogchi T. 1992 Effects of dexamethasone on the production of insulin-like growth factor-I and insulin-like growth factor binding proteins in primary cultures of rat hepatocytes. Biosci Biotechnol Biochem. S6(9):1396–1400.
  25. Unterman TG, Oehler DT, Murphy LJ, Lacson RG. 1991 Multihormonal regulation of insulin-like growth factor-binding protein-1 in rat H4IIE hepatoma cells: the dominant role of insulin. Endocrinology. 128:2693–2701.[Abstract/Free Full Text]
  26. Luo J, Reld RE, Murphy LJ. 1990 Dexamethasone increases hepatic insulin-like growth factor binding protein-1 (IGFBP-1) mRNA and serum IGFBP-1 concentrations in the rat. Endocrinology. 127:1456–1462.[Abstract/Free Full Text]
  27. Unterman TG, Jentel JJ, Oehler DT, Lacson RG, Hofert JF. 1993 Effects of glucocorticoids on circulating levels and hepatic expression of insulin-like growth factor (IGF) binding proteins and IGF-I in the adrenalectomized streptozotocin diabetic rat. Endocrinology. 133:2531–2539.[Abstract/Free Full Text]
  28. Conover CA, Divertie GD, Lee PD. 1993 Cortisol increases plasma insulin-like growth factor binding protein-1 in humans. Acta Endocrinol (Copenh). 128:140–143.[Abstract/Free Full Text]
  29. Lewitt M, Denyer GS, Cooney GJ, Baxter RC. 1991 Insulin-like growth factor-binding protein-1 modulates blood glucose levels. Endocrinology. 129:2254–2256.[Abstract/Free Full Text]



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