The synthetic human growth hormone fragment (32–38) increases glucose uptake in the conscious dog

Abstract

Abstract. hGH32-38 was tested to determine if the peptide could affect hepatic glucose production in the conscious dog under basal conditions (euglycemia) or if it could enhance glucose uptake when hyperglycemia was induced. hGH32-38 (1.6 nmol · kg−1 · min−1) or vehicle was infused in a cross-over design study into each of 4 conscious 16 h-fasted dogs for 3 h (0–180 min) following a 40 min control period. At 90 min, plasma glucose was raised to and maintained at 9.4 mmol/l by glucose infusion for 3 h (until 270 min). Neither hGH32-38 nor vehicle infusion had a significant effect on insulin and glucagon levels or on tracer determined ([3-3H]glucose) glucose production. As a result, neither treatment changed plasma glucose (5.72 ± 0.17 to 5.78 ± 0.17 mmol/l with hGH32-38; 5.50 ± 0.22 to 5.50 ± 0.17 mmol/l with vehicle). Induction of hyperglycemia (9.4 mmol/l) caused glucagon concentrations to fall similarly to about 50 ng/l with and without hGH32-38. Insulin rose to similar levels in both protocols, yet more glucose was required to maintain the same hyperglycemia with hGH32-38 (135– 180 min) (74.9 ± 12.7 vs 43.7 ± 7.1 μmol · kg−1 · min−1, P < 0.05). In summary, hGH32-38 significantly increased glucose disposition during hyperglycemia and this effect may be attributed to enhanced insulin action or to an insulin independent action of the peptide.

Effects of Hypophysectomy and the Insulin-Like and Anti-Insulin Pituitary Peptides on Carbohydrate Metabolism in Yellow Avy/A (BALB/c x VY)F1 Hybrid Mice

“…More recent studies indicated that administration of hGH or hGH32-46 to obese yellow mice enhanced responses to insulin action (1 1, 15, 16). In addition, similar effects were shown by others with hGH31-44 in rats (47), with hGH32-46 in rats (12) and in dogs (9), and with hGH32-38 in dogs (10). Upon further experimentation, we not only confirmed their observations in mice but also found no statistically significant change in insulin receptor number (334 k 57 fmol/mg vs 250 & 45 fmol/ mg) nor binding affinity (.03 nM-' vs 0.5 nM-' by treatment with hGHI-43 when compared with that of saline-treated controls.…”

“…In the present study, we did not observe any change in insulin levels by treatment with hGH1-43 or hGH to lean agouti, obese yellow, and hypophysectomized yellow mice; only hGH 1-43 enhanced insulin actions in yellow mice. The suggestion by Stevenson et al (9,10) that these closely related peptides act through different mechanisms is doubtful. Our recent observation supports the work of Frigeri et al (11) which showed that the peptides alter tissue sensitivity to insulin either by affecting insulin binding or by another postreceptor mechanism.…”

“…The increased sensitivity to insulin could also have been due to the decrease in the high circulating levels of insulin in hypophysectomized yellow mice. Stevenson et al (9) indicated that insulin-like action (increased glucose uptake) of hGH32-46 in dogs could be explained by enhanced secretion of insulin, while hGH32-38 appeared to potentiate insulin action without changing insulin levels (10). In the present study, we did not observe any change in insulin levels by treatment with hGH1-43 or hGH to lean agouti, obese yellow, and hypophysectomized yellow mice; only hGH 1-43 enhanced insulin actions in yellow mice.…”

“…Some recent reports have indicated that the amino-terminal fragments of hGH showed an insulin-potentiating action (9)(10)(11)(12)(13)(14)(15)(16), while the carboxyl terminus was antagonistic to insulin action (17). Recent studies with an amino-terminal portion of hGH (hGH1-43) have shown that it enhances insulin action on adipose tissue from obese mice and diabetic rats and potentiates the action of insulin on glucose clearance (1 1, [13][14][15][16].…”

The use of multiple‐pin peptide synthesis in an analysis of the continuous epitopes recognised by various anti‐(recombinant bovine growth hormone) sera

“…Previously our laboratory has demonstrated that polyclonal antisera against rat growth hormone (rGH) immunoneutraliscs the biological activity of the hormone by inhibiting neonatal rat growth and decreasing circulating insulin-like growth factor 1 levels [13,14]. GH itselfhas a multiplicity of biological actions including stimulation of somatic growth, effects on body composition, insulin-like and diabetogenic effects (reviewed in [15]), and there is some evidence that these different biologically active domains reside in different parts of the hormone [16]. Therefore, we decided to scan the GH molecule to identify continuous epitopes within the protein with the intention of identifying populations of antibodies which may be useful for selectively manipulating the activity of the hormone.…”