scholarly journals Polyethylene glycol-conjugated growth hormone-releasing hormone is long acting and stimulates GH in healthy young and elderly subjects

2005 ◽  
Vol 153 (2) ◽  
pp. 249-256 ◽  
Author(s):  
A Munafo ◽  
T X Q Nguyen ◽  
O Papasouliotis ◽  
H Lécuelle ◽  
A Priestley ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Polyethylene Glycol ◽  
Serum Insulin ◽  
Repeated Administration ◽  
The Elderly ◽  
Elderly Subjects ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Young Subjects ◽  
Long Acting

Objective: The clinical use of growth hormone-releasing hormone (GHRH) is limited by its short half-life. Polyethylene glycol-conjugated GHRH (PEG-GHRH) was developed to provide increased stability compared with the currently available GHRH(1–29). This study aimed to evaluate the safety, tolerability and pharmacodynamics of PEG-GHRH. Design: PEG-GHRH was administered by subcutaneous injection to young healthy men (n = 12) and elderly men and women (aged > 60 years; n = 20). Results: In both groups, administration of PEG-GHRH generated a clear increase in circulating GH compared with placebo. Following single-dose (0.25, 0.5, 2 or 4 mg) administration to young subjects, the effect persisted for 12 h, but a sustained increase was observed on repeated administration to the elderly. Serum insulin-like growth factor-I also increased in response to PEG-GHRH treatment. Injection-site reactions were more frequent with PEG-GHRH compared with placebo, but these were mild and transient; other adverse events were similar to those observed after placebo. Some impairment of glucose tolerance was observed in the elderly following repeated administration of PEG-GHRH. Antibodies to GHRH were not observed. Conclusions: PEG-GHRH offers the possibility of less frequent dosing compared with GHRH. This possibility deserves further clinical testing.

Reduced Efficacy of Growth Hormone-Releasing Hormone in Modulating Sleep Endocrine Activity in the Elderly

1997 ◽  
Vol 18 (5) ◽  
pp. 491-495 ◽  
Author(s):  
J Guldner ◽  
T Schier ◽  
E Friess ◽  
M Colla ◽  
F Holsboer ◽  
...  
Keyword(s):  
Growth Hormone ◽  
The Elderly ◽  
Growth Hormone Releasing Hormone ◽  
Endocrine Activity ◽  
Releasing Hormone

scholarly journals Beneficial effects of growth hormone-releasing hormone agonists on rat INS-1 cells and on streptozotocin-induced NOD/SCID mice

2015 ◽  
Vol 112 (44) ◽  
pp. 13651-13656 ◽  
Author(s):  
Xianyang Zhang ◽  
Tengjiao Cui ◽  
Jinlin He ◽  
Haibo Wang ◽  
Renzhi Cai ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cell Proliferation ◽  
Serum Insulin ◽  
Severe Combined Immunodeficiency ◽  
Scid Mice ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Rat Islets ◽  
Therapeutic Benefits ◽  
Glucose Challenge

Agonists of growth hormone-releasing hormone (GHRH) have been previously reported to promote growth, function, and engraftment of islet cells following transplantation. Here we evaluated recently synthesized GHRH agonists on the proliferation and biological functions of rat pancreatic β-cell line (INS-1) and islets. In vitro treatment of INS-1 cells with GHRH agonists increased cell proliferation, the expression of cellular insulin, insulin-like growth factor-1 (IGF1), and GHRH receptor, and also stimulated insulin secretion in response to glucose challenge. Exposure of INS-1 cells to GHRH agonists, MR-356 and MR-409, induced activation of ERK and AKT pathways. Agonist MR-409 also significantly increased the levels of cellular cAMP and the phosphorylation of cAMP response element binding protein (CREB) in INS-1 cells. Treatment of rat islets with agonist, MR-409 significantly increased cell proliferation, islet size, and the expression of insulin. In vivo daily s.c. administration of 10 μg MR-409 for 3 wk dramatically reduced the severity of streptozotocin (STZ)-induced diabetes in nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice. The maximal therapeutic benefits with respect to the efficiency of engraftment, ability to reach normoglycemia, gain in body weight, response to high glucose challenge, and induction of higher levels of serum insulin and IGF1 were observed when diabetic mice were transplanted with rat islets preconditioned with GHRH agonist, MR-409, and received additional treatment with MR-409 posttransplantation. This study provides an improved approach to the therapeutic use of GHRH agonists in the treatment of diabetes mellitus.

Sign in / Sign up

Export Citation Format

Share Document