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Effects of the Amino-Terminal Portion of Human Growth Hormone on Glucose Clearance and Metabolism in Normal, Diabetic, Hypophysectomized, and Diabetic-Hypophysectomized Rats^*

Lutcher Brown Department of Biochemistry, Whittier Institute for Diabetes and Endocrinology La Jolla, California 92037

Address all correspondence and requests for reprints to: Mohammed A. M. Salem, Ph.D., Whittier Institute for Diabetes and Endocrinology, 9894 Genesee Avenue, La Jolla, California 92037.

Abstract

A naturally occurring pituitary peptide, human (h) GH-(l-43) potentiates insulin action. The present study has compared the effects of acute (30–60 min) and chronic (3-6 days) injections of synthetic hGH-(l–43), hGH, and insulin in normal, diabetic, hypophysectomized, and diabetic-hypophysectomized rats. Male rats (150–250 g) received injections of saline, insulin (50–200 mU), hGH (200 µg), or hGH-(l–43) (200-400 ng) with or without insulin. Hormone and glucose were injected simultaneously for glucose tolerance tests. Basal and insulinstimulated [U-¹⁴C]glucose oxidation to ¹⁴CO₂ in adipose tissue were measured in vitro after in vivo treatments; insulin release by isolated pancreatic islets was determined in vitro. Acute injections of hGH-(l–43) with insulin dramatically increased glucose clearance in diabetic (P < 0.05) and hypophysectomized (P < 0.01) rats. In diabetic-hypophysectomized rats acute injections of hGH-(l–43) significantly lowered the elevated basal blood glucose level (P < 0.025) and stimulated [U-¹⁴C]glucose oxidation to ¹⁴CO₂ in adipose tissue (P < 0.05); it did not increase the glucose clearance rate during glucose administration. Chronic treatment of diabetic rats with hGH-(l–43) did not lower the elevated blood glucose level significantly, but it stimulated [U-¹⁴C]glucose oxidation to ¹⁴CO₂ in adipose tissue; the oxidation was further stimulated by treatment with insulin. Chronic injections of hGH-(l–43) slightly lowered blood glucose levels in hypophysectomized rats (P < 0.025) despite a diminished release in vitro of insulin from pancreatic islets (P < 0.05). Therefore, these experiments show hGH-(1–43) to be an insulin potentiator that increases insulin-stimulated glucose clearance and glucose oxidation without an increase in insulin secretion, and they suggest that the peptide may have a physiological role in regulating carbohydrate metabolism. (Endocrinology 123: 1565–1576, 1988)

Footnotes

^* This work was supported by NIH Biomedical Research Support Grant S07RR-05876 and the Scripps Memorial Hospital Foundation.

Received February 8, 1988.

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