The effect of polyethylene glycol recombinant human growth hormone on growth and glucose metabolism in hypophysectomized rats

ArticleinGrowth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 22(1):30-5 · February 2012with9 Reads
Impact Factor: 1.41 · DOI: 10.1016/j.ghir.2011.12.002 · Source: PubMed

To study the effect of polyethylene glycol recombinant human growth hormone on growth and glucose metabolism in hypophysectomized rats, and compare the effect of treatment between recombinant human growth hormone (rhGH) and polyethylene glycol rhGH (PEG-rhGH). Hypophysectomy was performed in juvenile rats to build the animal model of GH deficiency. The hypophysectomized animals were randomly assigned into three groups and treated with saline (negative control, n=20), rhGH (n=20) and PEG-rhGH (n=20). A sham operation was performed to set up the normal control (n=20). Body weight, body length and tail length were recorded every 2days for a 14-day treatment and bone growth was measured at the end of therapy. Glucose infusion rate (GIR) determined by euglycemic hyperinsulinemic clamp was used to evaluate insulin sensitivity after GH treatment. We also examined plasma glucose and serum insulin levels Compared with the negative control, the body weight, body length, tail length and bone growth increased significantly in hypophesectomized rats treated by GH (P<0.01). Although the weight gain in the first 10days was higher in the PEG-rhGH group than in the rhGH group (P<0.05), the growth promoting effect was similar between rhGH and PEG-rhGH (P>0.05). Neither rhGH nor PEG-rhGH impaired glucose tolerance of rats after hypophesectomy. Compared with negative controls, according to decreased serum insulin, reduced insulin expression in pancreatic cells and increased GIR in the clamp, both rhGH and PEG-rhGH groups had improved insulin sensitivity within 14 days (P<0.01). However, with prolonged treatment, the GIR in the rhGH-treated rats decreased significantly (P<0.05); while PEG-rhGH did not interfere with GIR, even after a doubled dose (P>0.05). PEG-rhGH had the same linear growth promoting efficacy as unmodified rhGH. The short-term GH replacement could improve insulin sensitivity in hypophysectomized rats, especially after PEGylation.

    • "Mono-PEGylation of bovine lactoferrin, an anticancer iron-binding glycoprotein, enhanced its resistance towards proteolytic degradation in the GI fluid and increased its oral absorption (10-folds) in comparison to unmodified lactoferrin [47] . A PEGylated version of human growth hormone represented similar activity, in terms of growth, as unmodified form but enhanced the sensitivity of insulin in hypophysectomized rats when tested with respect to glucose metabolism [48]. Youn et al. developed a Lys 18 -amine specific PEGylated derivative of salmon calcitonin for oral administration and results suggested that PEGylated protein has enhanced resistance against pancreatic peptidases and brush-border peptidases along with reduced systemic clearance. "
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    Full-text · Article · Oct 2014 · Journal of Controlled Release
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