Effects of the amino-terminal portion of human growth hormone on glucose clearance and metabolism in normal, diabetic, hypophysectomized, and diabetic-hypophysectomized rats.
A naturally occurring pituitary peptide, human (h) GH-(1-43) potentiates insulin action. The present study has compared the effects of acute (30-60 min) and chronic (3-6 days) injections of synthetic hGH-(1-43), 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 micrograms), or hGH-(1-43) (200-400 micrograms) with or without insulin. Hormone and glucose were injected simultaneously for glucose tolerance tests. Basal and insulin-stimulated [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-(1-43) with insulin dramatically increased glucose clearance in diabetic (P less than 0.05) and hypophysectomized (P less than 0.01) rats. In diabetic-hypophysectomized rats acute injections of hGH-(1-43) significantly lowered the elevated basal blood glucose level (P less than 0.025) and stimulated [U-14C]glucose oxidation to 14CO2 in adipose tissue (P less than 0.05); it did not increase the glucose clearance rate during glucose administration. Chronic treatment of diabetic rats with hGH-(1-43) 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-(1-43) slightly lowered blood glucose levels in hypophysectomized rats (P less than 0.025) despite a diminished release in vitro of insulin from pancreatic islets (P less than 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.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D005951:Glucose Tolerance Test; D006019:Glycolysis / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology*; D007016:Hypophysectomy; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; C056878:somatotropin (1-43); D013006:Growth Hormone