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Combination therapy with acipimox enhances the effect of growth hormone treatment on linear body growth in the normal and small-for-gestational-age rat

Combination therapy with acipimox enhances the effect of growth hormone treatment on linear body growth in the normal and small-for-gestational-age rat
Combination therapy with acipimox enhances the effect of growth hormone treatment on linear body growth in the normal and small-for-gestational-age rat
Growth hormone (GH) therapy is often associated with adverse side effects, including impaired insulin sensitivity. GH treatment of children with idiopathic short stature does not lead to an optimized final adult height. It has been demonstrated that FFA reduction induced by pharmacological antilipolysis can stimulate GH secretion per se in both normal subjects and those with GH deficiency. However, to date, no investigation has been undertaken to establish efficacy of combination treatment with GH and FFA regulators on linear body growth. Using a model of maternal undernutrition in the rat to induce growth-restricted offspring, we investigated the hypothesis that combination treatment with GH and FFA regulators can enhance linear body growth above that of GH alone. At postnatal day 28, male offspring of normally nourished mothers (controls) and offspring born with low birth weight [small for gestational age (SGA)] were treated with saline, GH, or GH (5 mg.kg(-1).day(-1)) in combination with acipimox (GH + acipimox, 20 mg.kg(-1).day(-1)) or fenofibrate (GH + fenofibrate, 30 mg.kg(-1).day(-1)) for 40 days. GH plus acipimox treatment significantly enhanced linear body growth in the control and SGA animals above that of GH, as quantified by tibial and total body length. Treatment with GH significantly increased fasting plasma insulin, insulin-to-glucose ratio, and plasma volumes in control and SGA animals but was not significantly different between saline and GH-plus-acipimox-treated animals. GH-induced lipolysis was blocked by GH plus acipimox treatment in both control and SGA animals, concomitant with a significant reduction in fasting plasma FFA and insulin concentrations. This is the first study to show that GH plus acipimox combination therapy, via pharmacological blocking of lipolysis during GH exposure, can significantly enhance the efficacy of GH in linear growth promotion and ameliorate unwanted metabolic side effects
growth hormone, acipimox, insulin, free fatty acids
0193-1849
E1212-E1219
Vickers, M.H.
0fa7133b-53c7-4b48-9863-1b55e53baa5e
Hofman, P.L.
c8936c79-0cc8-4de9-8b73-db6e6933ceb3
Gluckman, P.D.
492295c0-ef71-4871-ad5a-771c98e1059a
Lobie, P.E.
d1d009de-75f1-4460-8478-e46b6104515f
Cutfield, W.S.
6b21b06f-1f06-4601-b5e9-91b2c6336770
Vickers, M.H.
0fa7133b-53c7-4b48-9863-1b55e53baa5e
Hofman, P.L.
c8936c79-0cc8-4de9-8b73-db6e6933ceb3
Gluckman, P.D.
492295c0-ef71-4871-ad5a-771c98e1059a
Lobie, P.E.
d1d009de-75f1-4460-8478-e46b6104515f
Cutfield, W.S.
6b21b06f-1f06-4601-b5e9-91b2c6336770

Vickers, M.H., Hofman, P.L., Gluckman, P.D., Lobie, P.E. and Cutfield, W.S. (2006) Combination therapy with acipimox enhances the effect of growth hormone treatment on linear body growth in the normal and small-for-gestational-age rat. American Journal of Physiology: Endocrinology and Metabolism, 291 (6), E1212-E1219. (doi:10.1152/ajpendo.00614.2005).

Record type: Article

Abstract

Growth hormone (GH) therapy is often associated with adverse side effects, including impaired insulin sensitivity. GH treatment of children with idiopathic short stature does not lead to an optimized final adult height. It has been demonstrated that FFA reduction induced by pharmacological antilipolysis can stimulate GH secretion per se in both normal subjects and those with GH deficiency. However, to date, no investigation has been undertaken to establish efficacy of combination treatment with GH and FFA regulators on linear body growth. Using a model of maternal undernutrition in the rat to induce growth-restricted offspring, we investigated the hypothesis that combination treatment with GH and FFA regulators can enhance linear body growth above that of GH alone. At postnatal day 28, male offspring of normally nourished mothers (controls) and offspring born with low birth weight [small for gestational age (SGA)] were treated with saline, GH, or GH (5 mg.kg(-1).day(-1)) in combination with acipimox (GH + acipimox, 20 mg.kg(-1).day(-1)) or fenofibrate (GH + fenofibrate, 30 mg.kg(-1).day(-1)) for 40 days. GH plus acipimox treatment significantly enhanced linear body growth in the control and SGA animals above that of GH, as quantified by tibial and total body length. Treatment with GH significantly increased fasting plasma insulin, insulin-to-glucose ratio, and plasma volumes in control and SGA animals but was not significantly different between saline and GH-plus-acipimox-treated animals. GH-induced lipolysis was blocked by GH plus acipimox treatment in both control and SGA animals, concomitant with a significant reduction in fasting plasma FFA and insulin concentrations. This is the first study to show that GH plus acipimox combination therapy, via pharmacological blocking of lipolysis during GH exposure, can significantly enhance the efficacy of GH in linear growth promotion and ameliorate unwanted metabolic side effects

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More information

Published date: December 2006
Keywords: growth hormone, acipimox, insulin, free fatty acids

Identifiers

Local EPrints ID: 61584
URI: http://eprints.soton.ac.uk/id/eprint/61584
ISSN: 0193-1849
PURE UUID: 51cc56a7-a92b-4685-aed2-ccd089061778

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Date deposited: 10 Sep 2008
Last modified: 15 Mar 2024 11:27

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Contributors

Author: M.H. Vickers
Author: P.L. Hofman
Author: P.D. Gluckman
Author: P.E. Lobie
Author: W.S. Cutfield

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