Biological characterization of purified native 20-kDa human growth hormone

Because of the propensity of the 20-kDa variant of human growth human (GH) to aggregate with itself and with 22-kDa human GH, it has been difficult to prepare monomeric 20-kDa GH in highly purified form. This has been a major complicating factor in determining whether 20-kDa GH has a biological activity profile distinct from that of 22-kDa GH. In the present study, native 20-kDa GH was isolated from a human GH dimer concentrate and purified by a procedure that included column electrophoresis in agarose suspension as a final separation step. This procedure yielded highly purified monomeric 20-kDa GH, which was contaminated to an extent of less than 1% with 22-kDa GH, and which exhibited only a small degree of dimerization upon storage. The native 20-kDa Gh was quite active in stimulating growth in hypophysectomized rats, when growth was assessed by body weight gain, longitudinal bone growth, the stimulation of sulfation of cartilage, and the elevation of serum IGF-1 level. However, in all of these growth assays, the 20-kDa GH was somewhat less active than the native 22-kDa GH to which it was compared; e.g., in the body weight gain and longitudinal bone growth assays, it had an estimated potency of 0.6 relative to the 22-kDa GH. The 20-kDa GH exhibited substantial diabetogenic activity when tested for the ability to raise fasting blood glucose concentration and to impair glucose tolerance in ob/ob mice. Also, the native 20-kDa GH had significant in vitro insulin-like activity, although its potency was approximately 20% that of the native 22-kDa GH to which it was compared. Thus, the biological activity profile of native 20-kDa GH differs from that of 22-kDa GH primarily in that insulin-like activity is markedly attenuated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26576/1/0000115.pd

Nerve regeneration and serum levels of insulin-like growth factor-I in rats with streptozotocin-induced insulin deficiency

Peripheral nerve regeneration was studied in female Sprague-Dawley rats with streptozotocin-induced insulin deficiency. Nerve regeneration was provoked by a crush lesion on the sciatic nerve 21 days after the streptozotocin injection. The regeneration was assessed by a pinch test at different time-points after injury. The rate ofregeneration in insulin-deficient animals, 2.5 mm/day, was significantly lower than in control animals, 2.9 mm/day(P 0.01). The streptozotocin-treated rats were found to have a 39% reduction in the serum level of insulin-like 1 growth factor-I (IGF-I)_compared to control rats (0.33 ± 0.22 μg/ml and 0.54 ± ml respectively, (P < 0.001). Insulin treatment 1830 1732 during the regeneration period completely restored the IGF-I level back to normal

Insulin-like growth factor I does not inhibit insulin secretion in adult human pancreatic islets in tissue culture.

Insulin-like growth factor I (IGF-I) has been found to increase insulin sensitivity and suppress insulin secretion, thereby having a potential interest as a therapeutic agent for non-insulin-dependent diabetes mellitus (NIDDM). The aim of the present study was to investigate the direct actions of IGF-I (400 ng/ml) on human pancreatic islets, or on rat pancreatic islets, during a 48 h period in tissue culture. Insulin-like growth factor I did not affect medium insulin accumulation, DNA or insulin content or short-term glucose-induced insulin release of human islets. However, in rat islets the peptide induced a significant decrease in the insulin increase ratio in response to 16.7 mmol/l glucose. In conclusion, the present data suggest that IGF-I does not directly affect the function of human pancreatic beta-cells. If this in vitro data can be extrapolated to the in vivo situation, it suggests that the observed inhibitory effects of IGF-I on serum insulin levels may be secondary to peripheral effects of the peptide.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

A comparison of the effects of insulin-like growth factor-I, insulin and combined infusions of insulin and insulin-like growth factor-I on glucose metabolism in dogs.

The effect of infusions of recombinant insulin-like growth factor-I (IGF-I) (34, 103 or 688 pmol kg-1 min-1), insulin (3.4, 10.3 or 68.8 pmol kg-1 min-1) or combined infusions (34 pmol IGF-I + 3.4 pmol kg-1 min-1 insulin or 103 pmol IGF-I + 3.4 pmol kg-1 min-1 insulin) on glucose metabolism was investigated in dogs using a [3-3H]-glucose infusion and euglycaemic clamp. All insulin doses decreased glucose production rate (Ra) in a dose-dependent manner (P < 0.05). All IGF-I doses decreased glucose Ra (P < 0.05) but this decrease was not dose dependent. The decrease in glucose Ra with the combined infusion of 34 pmol kg-1 min-1 IGF-I + 3.4 pmol kg-1 min-1 insulin was greater than 34 pmol kg-1 min-1 IGF-I (P < 0.05) but not different from 3-4 pmol kg-1 min-1 insulin. All insulin and IGF-I doses increased glucose utilization rate (Rd) in a dose-dependent manner (P < 0.01). The increase in glucose utilization was greater following both combined infusions than with either component infused alone (P < 0.05). Although at the doses selected, insulin and IGF-I had similar effects on glucose utilization with additive effects when the two peptides were combined, IGF-I was less effective than insulin in suppressing glucose production

Changes in serum somatomedin and growth hormone concentrations after 3 weeks oestrogen substitution in post-menopausal women; a pilot study

Oestrogens have a preventive effect on bone loss in post-menopausal women; however, little is known about their mechanism of action. The aim of this study was to investigate the changes in somatomedins (SM) and growth hormone (GH) concentrations in serum in post-menopausal women after 3 weeks of substitution with 20 micrograms ethinyloestradiol. A significant decrease was observed in the mean serum levels of SM, measured by bioassay (0.66 +/- 0.07 vs 0.38 +/- 0.07, P less than 0.01), radioimmunoassay (0.62 +/- 0.08 vs 0.34 +/- 0.03, P less than 0.01) and radioreceptorassay (1.14 +/- 0.11 vs 0.90 +/- 0.09, P less than 0.01). The mean serum GH concentration increased (9.4 +/- 3.2 vs 16.5 +/- 4.6, P less than 0.01). A positive role of SM and GH in the changes of bone metabolism after oestrogen substitution in post-menopausal women is discusse