Growth hormone responses to growth hormone‐releasing hormone and clonidine in patients with type I diabetes and in normal controls: effect of age, body mass index and sex

Jacobs, M. L.; Nathoe, Hendrik M.; Blankestijn, P. J.; Stijnen, T.; Weber, R. F. A.

doi:10.1046/j.1365-2265.1996.713534.x

Cited by 9 publications

(6 citation statements)

References 39 publications

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“…Type 1 diabetic patients were shown to exhibit elevated GH levels and exaggerated GH response to GHRH (46,47), which in turn may contribute to dyslipidemia (48). Besides stimulating GH production in the pituitary gland, GHRH also exerts peripheral effects through full-length pituitary type receptors and splice variant 1 receptors that are expressed in various organs, including lung, heart, stomach, small intestine, colon, and kidney (22)(23)(24).…”

Section: Mia-602 Improves Vascular Function In T1dmentioning

confidence: 99%

Role of growth hormone-releasing hormone in dyslipidemia associated with experimental type 1 diabetes

Romero

Lucas

Dou

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Dyslipidemia associated with triglyceride-rich lipoproteins (TRLs) represents an important residual risk factor for cardiovascular and chronic kidney disease in patients with type 1 diabetes (T1D). Levels of growth hormone (GH) are elevated in T1D, which aggravates both hyperglycemia and dyslipidemia. The hypothalamic growth hormone-releasing hormone (GHRH) regulates the release of GH by the pituitary but also exerts separate actions on peripheral GHRH receptors, the functional role of which remains elusive in T1D. In a rat model of streptozotocin (STZ)-induced T1D, GHRH receptor expression was found to be up-regulated in the distal small intestine, a tissue involved in chylomicron synthesis. Treatment of T1D rats with a GHRH antagonist, MIA-602, at a dose that did not affect plasma GH levels, significantly reduced TRL, as well as markers of renal injury, and improved endothelial-dependent vasorelaxation. Glucagon-like peptide 1 (GLP-1) reduces hyperglucagonemia and postprandial TRL, the latter in part through a decreased synthesis of apolipoprotein B-48 (ApoB-48) by intestinal cells. Although plasma GLP-1 levels were elevated in diabetic animals, this was accompanied by increased rather than reduced glucagon levels, suggesting impaired GLP-1 signaling. Treatment with MIA-602 normalized GLP-1 and glucagon to control levels in T1D rats. MIA-602 also decreased secretion of ApoB-48 from rat intestinal epithelial cells in response to oleic acid stimulation in vitro, in part through a GLP-1-dependent mechanism. Our findings support the hypothesis that antagonizing the signaling of GHRH in T1D may improve GLP-1 function in the small intestine, which, in turn, diminishes TRL and reduces renal and vascular complications.yslipidemia frequently accompanies type 1 diabetes (T1D) and represents an important component of the disease, imposing cardiovascular risk and correlating with renal dysfunction (1, 2). Current clinical approaches directed toward diabetic dyslipidemia, including changes in lifestyle, stringent glycemic control, lipid lowering therapy, or combinations thereof, offer limited benefit, thus emphasizing the need for the development of novel therapies.Therapy with statins reduces major cardiovascular events largely through reduction of low-density lipoprotein (LDL) cholesterol (3). Still, an important residual cardiovascular risk, which is independent of LDL cholesterol levels, remains (4-8). Chylomicrons (CMs), chylomicron remnants (CMRs), and very low-density lipoproteins (VLDLs), cumulatively known as triglyceride-rich lipoproteins (TRLs), contribute significantly to postprandial lipemia (9). Increased TRL levels represent an important additional risk factor for atherosclerosis (10), particularly in subjects with diabetes or the metabolic syndrome (11).Glucagon-like peptide 1 (GLP-1), an incretin hormone secreted in the small intestine, promotes postprandial insulin release, thereby reducing blood glucose levels (12). Endogenous GLP-1 also reduces postprandial glucagon secretion through direct actions on p...

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Section: Mia-602 Improves Vascular Function In T1dmentioning

confidence: 99%

Role of growth hormone-releasing hormone in dyslipidemia associated with experimental type 1 diabetes

Romero

Lucas

Dou

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…glucose load. In insulin-dependent diabetes mellitus, however, this correlation is absent (16) and GHRHstimulated GH secretion is considered inappropriately high in view of the hyperglycaemia in these patients. The heterogeneity in the GH response to GHRH is greater in diabetes mellitus than in healthy individuals, and the response depends on the degree of metabolic alteration.…”

Section: Non-insulin-dependent Diabetes Mellirusmentioning

confidence: 99%

Growth hormone secretagogues in pathological states: diagnostic implications

Popović¹,

Micić²,

Damjanović³

et al. 1997

Acta Paediatrica

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Golubicic I, Nikitovic M, Mitrovic N, Dieguez C, Casanueva FF. Growth hormone secretagogues in pathological states: diagnostic implications. Acta Paediatr 1997; Suppl423:97-101. Stockholm.The identification and cloning of the receptor for synthetic growth hormone (GH) secretagogues, even before the endogenous ligand has been identified or its precise physiological role established, suggests that there is a novel target of action for this class of drug. In an attempt to select patients who will benefit from GH treatment, GH secretagogues are being evaluated for their usefulness in diagnosing GH deficiency. The effects of GH-releasing peptides (GHRPs) on GH release as a function of age and metabolic status, and in different neuroendocrine pathologies, are described, as are the different mechanisms of action, potency and reproducibility of the response to GHRPs compared with GH-releasing hormone (GHRH). GHRPs offer the advantage over GHRH in natural models of deranged GH secretion in that, in various metabolic states (e.g. obesity, anorexia nervosa and non-insulin-dependent diabetes mellitus), the GH response to GHRH is more impaired than it is to GHRPs. However, in some neuroendocrine pathologies, the reverse is true. Thus, both secretagogues provide separate information on the physiological status of somatotrophs. Growth hormone-releasing peptide-6, growth hormone-releasing hormone, hexarelin, metabolic derangements, neuroendocrine pathologies V Popovic, Institute of Endocrinology, University Clinical Centre, Belgrade, Yugoslavia ISSN 0803-5326Neuroendocrine control of the pulsatile pattern of growth hormone (GH) secretion is complex. The multicomponent nature of the neuronal network and the complex transcriptional machinery that regulates GH gene expression have been characterized (1). In addition to the specific hypothalamic regulatory' hormones -GHreleasing hormone (GHRH) and somatdstatinother substances can influence GH secretion, namely pituitary cyclic AMP, oestrogens, glucocorticoids, GH-releasing peptides (GHRPs) and their nonpeptide pharmacological analogues. Metabolic states, such as obesity and malnutrition, and even metabolites, such as glucose, amino acids and free fatty acids, also participate in the control of GH secretion (2-4).In an attempt to improve our understanding of the complicated regulation of GH secretion in humans, and its relevance to clinical practice, we have studied the effects of GHW-6 and hexarelin, which is an analogue of GHRP-6 containing a 2-methyl substitution of D-tryptophan. Such small synthetic hexapeptides have no sequence homology with GHRH and are characterized by their high potency and selectivity in the reIease of GH in different clinical conditions (metabolic and neuroendocrine) associated with altered or impaired GH secretion. The well-known GHRP-6 (5, 6) acts through a specific receptor. This has recently been cloned and supports the existence of a second route of GH regulation, although the endogenous ligand for this receptor has not yet been identified. The GHRP-6 ...

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“…It is unclear, however, whether this inhibition of GH secretion is caused by the blood glucose level itself or by the secondary rise in insulin levels. In patients with diabetes, GH levels are abnormally high and the response to GH stimuli is exaggerated, suggesting a central derangement caused by glucose levels, FFA, IGF‐1 or insulin 17–19 . In patients with diabetes, an elevated set point for the reactivity to blood glucose levels of the pituitary‐adrenal axis has been described either as a consequence or a cause of deranged carbohydrate metabolism or insulin insensitivity 20 …”

Section: Introductionmentioning

confidence: 99%

“…In patients with diabetes, GH levels are abnormally high and the response to GH stimuli is exaggerated, suggesting a central derangement caused by glucose levels, FFA, IGF-1 or insulin. [17][18][19] In patients with diabetes, an elevated set point for the reactivity to blood glucose levels of the pituitary-adrenal axis has been described either as a consequence or a cause of deranged carbohydrate metabolism or insulin insensitivity. 20 Whether the pituitary hormone release in normal subjects is related to blood glucose levels in a situation of normoglycaemia is not clear.…”

Section: Introductionmentioning

confidence: 99%

The impact of blood glucose levels on stimulated adrenocorticotropin hormone and growth hormone release in healthy subjects

Jakobsdottir

Twisk

Drent

2009

Clinical Endocrinology

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Growth hormone responses to growth hormone‐releasing hormone and clonidine in patients with type I diabetes and in normal controls: effect of age, body mass index and sex

Cited by 9 publications

References 39 publications

Role of growth hormone-releasing hormone in dyslipidemia associated with experimental type 1 diabetes

Role of growth hormone-releasing hormone in dyslipidemia associated with experimental type 1 diabetes

Growth hormone secretagogues in pathological states: diagnostic implications

The impact of blood glucose levels on stimulated adrenocorticotropin hormone and growth hormone release in healthy subjects

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