The cardiovascular phenotype of a mouse model of acromegaly

Izzard, Ashley S.; Emerson, Michael; Prehar, Sukhpal; Neyses, Ludwig; Trainer, Peter J; List, Edward O.; Kopchick, John J.; Heagerty, AM

doi:10.1016/j.ghir.2008.12.006

Cited by 19 publications

(16 citation statements)

References 39 publications

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“…It has been demonstrated that impaired glucose tolerance is significantly correlated with the severity of acromegalic cardiomyopathy (Colao et al, 2000). Although cardiac hypertrophy is a consistent finding in various animal models of GH overexpression (Bollano et al, 2000; Izzard et al, 2009; Palmer et al, 2009), data on deterioration of cardiac function in these GH-Tg mice models is not as compelling. Recently, Izzard et al (2009) reported that despite cardiac enlargement and an increase in systolic blood pressure in bGH mice, cardiac vasculature and vascular contractile function was normal.…”

Section: Discussionmentioning

confidence: 99%

“…Although cardiac hypertrophy is a consistent finding in various animal models of GH overexpression (Bollano et al, 2000; Izzard et al, 2009; Palmer et al, 2009), data on deterioration of cardiac function in these GH-Tg mice models is not as compelling. Recently, Izzard et al (2009) reported that despite cardiac enlargement and an increase in systolic blood pressure in bGH mice, cardiac vasculature and vascular contractile function was normal. This encourages us to speculate that cardiovascular disease might not be a major factor in the accelerated aging phenotype of these transgenic mice, thereby also preventing any deterioration of glucose homeostasis in these GH-Tg mice.…”

Section: Discussionmentioning

confidence: 99%

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Glucose homeostasis and insulin sensitivity in growth hormone-transgenic mice: a cross-sectional analysis

Boparai

Arum²,

Khardori³

et al. 2010

Biological Chemistry

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In contrast to its stimulatory effects on musculature, bone, and organ development, and its lipolytic effects, growth hormone (GH) opposes insulin effects on glucose metabolism. Chronic GH overexposure is thought to result in insulin insensitivity and decreased blood glucose homeostatic control. Yet, despite the importance of this concept for basic biology, as well as human conditions of GH excess or deficiency, no systematic assessment of the impact of GH overexpression on glucose homeostasis and insulin sensitivity has been conducted. We report that male and female adult GH transgenic mice have enhanced glucose tolerance compared to littermate controls and this effect is not dependent on age or on the particular heterologous GH transgene used. Furthermore, increased glucose-stimulated insulin secretion, augmented insulin sensitivity, and muted gluconeogenesis were also observed in bovine GH overexpressing mice. These results show that markedly increased systemic GH concentration in GH-transgenic mice exerts unexpected beneficial effects on glucose homeostasis, presumably via a compensatory increase in insulin release. The counterintuitive nature of these results challenges previously held presumptions of the physiology of these mice and other states of GH overexpression or suppression. In addition, they pose intriguing queries about the relationships between GH, endocrine control of metabolism, and aging.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Glucose homeostasis and insulin sensitivity in growth hormone-transgenic mice: a cross-sectional analysis

Boparai

Arum²,

Khardori³

et al. 2010

Biological Chemistry

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“…However, based on cross-sectional analyses of various tissues, there are a number of specific pathological organ changes, including severe glomerulosclerosis and lipid accumulation in the kidney, fibrosis in the heart, and enhanced senescence in adipose tissue, as well as enlargement of most GH-sensitive tissues, with the liver and spleen experiencing the greatest disproportionate increase in size [17,18,19,20,21,22,23,24,25,26]. There is also evidence of impaired cardiac and vascular function [18,27,28,29,30], notable kidney damage [31,32], and a greater incidence and earlier onset of liver and mammary tumors [33,34]. We speculate that all of these pathologies likely contribute to the dramatically reduced lifespan at varying levels.…”

Section: Lessons From Gh Transgenic Micementioning

confidence: 99%

Glucose and Fat Metabolism in Acromegaly: From Mice Models to Patient Care

Dal¹,

List²,

Jørgensen³

et al. 2015

Neuroendocrinology

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Patients with active acromegaly are frequently insulin resistant, glucose intolerant, and at risk for developing overt type 2 diabetes. At the same time, these patients have a relatively lean phenotype associated with mobilization and oxidation of free fatty acids. These features are reversed by curative surgical removal of the growth hormone (GH)-producing adenoma. Mouse models of acromegaly share many of these characteristics, including a lean phenotype and proneness to type 2 diabetes. There are, however, also species differences with respect to oxidation rates of glucose and fat as well as the specific mechanisms underlying GH-induced insulin resistance. The impact of acromegaly treatment on insulin sensitivity and glucose tolerance depends on the treatment modality (e.g. somatostatin analogs also suppress insulin secretion, whereas the GH antagonist restores insulin sensitivity). The interplay between animal research and clinical studies has proven useful in the field of acromegaly and should be continued in order to understand the metabolic actions of GH.

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“…Interestingly, the hyperinsulinemia and impaired glucose tolerance that has been reported in young adult life, presumably due to the well-documented insulin-antagonizing effect of GH, appears to be somewhat attenuated in later life [99,100]. This may be an adaptation to the chronic high levels of GH and/or a consequence of disease progression and the end organ damage reported in these mice [101,106]. The cause of the premature death is likely multifactorial although increased neoplastic lesions are at least, in part, responsible as will be discussed in the later sections.…”

Section: Mice With Excess Gh Actionmentioning

confidence: 69%

Living Large: What Mouse Models Reveal about Growth Hormone and Obesity

Berryman

Householder

Lesende

et al. 2015

Energy Balance and Cancer

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Growth hormone (GH) regulates a broad spectrum of biological processes in addition to promoting longitudinal growth. As such, GH influences most organ and cellular systems in the body with adipose tissue being one of its wellestablished targets. This chapter will describe mouse lines with specific alteration in GH action. Mice with increased, decreased, and absence of GH action have a unique phenotype for which clinical equivalents exist (acromegaly, GH deficiency, and Laron syndrome, respectively). Interestingly, these mouse lines demonstrate adiposity profiles that are counterintuitive to health and longevity. That is, mice with excess GH action are lean but insulin resistant, prone to cancer, and short-lived (or "unhealthy lean"). On the other hand, mice with no GH action are obese but insulin sensitive, resistant to cancer, and long-lived (or "healthy obesity"). These extremes in GH action provide fascinating mouse strains with which to study the features of fat that are responsible for metabolic dysfunction and to explore traits that are obligatory for cancer or lifespan.

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The cardiovascular phenotype of a mouse model of acromegaly

Cited by 19 publications

References 39 publications

Glucose homeostasis and insulin sensitivity in growth hormone-transgenic mice: a cross-sectional analysis

Glucose homeostasis and insulin sensitivity in growth hormone-transgenic mice: a cross-sectional analysis

Glucose and Fat Metabolism in Acromegaly: From Mice Models to Patient Care

Living Large: What Mouse Models Reveal about Growth Hormone and Obesity

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