In poorly controlled insulin-dependent diabetes mellitus (IDDM), hyperglycemia fails to inhibit the pituitary response to growth hormone–releasing factor (GRF). To evaluate whether this derangement is reversed by a simultaneous elevation of circulating insulin, 0.3 μg/kg i.v. GRF 1–40 was administered to nine poorly controlled IDDM subjects (HbA1 > 11.1%) with and without concomitant infusion of insulin. In the absence of insulin, the poorly controlled IDDM subjects demonstrated a growth hormone response to GRF similar to that of nondiabetic subjects, despite marked hyperglycemia (∼ 16.8 mM). When insulin was infused into these same patients (insulin clamp) to produce combined hyperinsulinemia (528 ± 90 pM) and hyperglycemia (16.5 ± 1.98 mM), the GRF-induced growth hormone rise was markedly exaggerated (65 ± 11 vs. 20 ± 4 μg/L without insulin infusion, P < 0.001). This enhancement of GRF-stimulated growth hormone release by insulin was strikingly attenuated (22 ± 7 μg/L) in five well-controlled diabetic subjects studied under conditions of similar hyperinsulinemia (486 ± 84 pM) and hyperglycemia (16.41 ± 0.95 mM). In contrast, in nondiabetic subjects, acute hyperinsulinemia reduced the growth hormone response to GRF. We conclude that the failure of hyperglycemia to block the pituitary response to GRF in poorly controlled diabetes is not attributable to the lack of a coincident increase in circulating insulin. The paradoxical stimulatory effect of insulin on GRF-induced growth hormone release may contribute to the high spontaneous growth hormone levels characteristically seen in poorly controlled insulin-treated patients, and its attenuation after intensive insulin therapy may contribute to the reversal of growth hormone hypersecretion in well-controlled diabetic patients.
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Original Articles|
January 01 1992
Pituitary Response to Growth Hormone–Releasing Hormone in IDDM: Abnormal Responses to Insulin and Hyperglycemia
Martin Press;
Martin Press
Department of Medicine and Pediatrics and General Clinical Research Center, Yale University School of Medicine
New Haven, Connecticut
; the Department of Internal Medicine, University of Virginia School of Medicine
Charlottesville, Virginia
; and the Peptide Biology Laboratory, Salk Institute
San Diego, California
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Sonia Caprio;
Sonia Caprio
Department of Medicine and Pediatrics and General Clinical Research Center, Yale University School of Medicine
New Haven, Connecticut
; the Department of Internal Medicine, University of Virginia School of Medicine
Charlottesville, Virginia
; and the Peptide Biology Laboratory, Salk Institute
San Diego, California
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William V Tamborlane;
William V Tamborlane
Department of Medicine and Pediatrics and General Clinical Research Center, Yale University School of Medicine
New Haven, Connecticut
; the Department of Internal Medicine, University of Virginia School of Medicine
Charlottesville, Virginia
; and the Peptide Biology Laboratory, Salk Institute
San Diego, California
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Rhajat Bhushan;
Rhajat Bhushan
Department of Medicine and Pediatrics and General Clinical Research Center, Yale University School of Medicine
New Haven, Connecticut
; the Department of Internal Medicine, University of Virginia School of Medicine
Charlottesville, Virginia
; and the Peptide Biology Laboratory, Salk Institute
San Diego, California
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Michael Thorner;
Michael Thorner
Department of Medicine and Pediatrics and General Clinical Research Center, Yale University School of Medicine
New Haven, Connecticut
; the Department of Internal Medicine, University of Virginia School of Medicine
Charlottesville, Virginia
; and the Peptide Biology Laboratory, Salk Institute
San Diego, California
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Wylie Vale;
Wylie Vale
Department of Medicine and Pediatrics and General Clinical Research Center, Yale University School of Medicine
New Haven, Connecticut
; the Department of Internal Medicine, University of Virginia School of Medicine
Charlottesville, Virginia
; and the Peptide Biology Laboratory, Salk Institute
San Diego, California
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Jean Rivier;
Jean Rivier
Department of Medicine and Pediatrics and General Clinical Research Center, Yale University School of Medicine
New Haven, Connecticut
; the Department of Internal Medicine, University of Virginia School of Medicine
Charlottesville, Virginia
; and the Peptide Biology Laboratory, Salk Institute
San Diego, California
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Robert S Sherwin
Robert S Sherwin
Department of Medicine and Pediatrics and General Clinical Research Center, Yale University School of Medicine
New Haven, Connecticut
; the Department of Internal Medicine, University of Virginia School of Medicine
Charlottesville, Virginia
; and the Peptide Biology Laboratory, Salk Institute
San Diego, California
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Address correspondence and reprint requests to Dr. Robert S. Sherwin, Yale University School of Medicine, PO Box 3333, New Haven, CT 06510.
Diabetes 1992;41(1):17–21
Article history
Received:
December 14 1987
Revision Received:
September 27 1991
Accepted:
September 27 1991
PubMed:
1727733
Citation
Martin Press, Sonia Caprio, William V Tamborlane, Rhajat Bhushan, Michael Thorner, Wylie Vale, Jean Rivier, Robert S Sherwin; Pituitary Response to Growth Hormone–Releasing Hormone in IDDM: Abnormal Responses to Insulin and Hyperglycemia. Diabetes 1 January 1992; 41 (1): 17–21. https://doi.org/10.2337/diab.41.1.17
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