Effect of pyridostigmine on the growth hormone response to growth hormone-releasing hormone in lean and obese type II diabetic patients

Giustina, Andrea; Bresciani, Enrico; Tassi, Carla; Girelli, Angela; Valentini, Umberto

doi:10.1016/0026-0495(94)90273-9

Cited by 24 publications

(10 citation statements)

References 33 publications

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“…The low IGF-1 availability contributes to sustain the relative GH hypersecretion due to the lack of the feedback negative signal at the hypothalamuspituitary axis [93]. In type 2 diabetes, chronic hyperglycemia in the presence of normal or increased insulin causes an increase in hypothalamic somatostatin tone with consequent impairment of GH secretion [94]. In this clinical context, IGF-1 values are variable in relationship with different degrees of insulin resistance and pancreatic beta cell dysfunction which reduce the ability of insulin to suppress IGFBP-1 synthesis by the liver [95].…”

Section: Gh/igf-1 Axis In Diabetes Mellitusmentioning

confidence: 99%

Insulin and GH–IGF-I axis: endocrine pacer or endocrine disruptor?

et al. 2014

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Growth hormone/insulin-like growth factor (IGF) axis may play a role in maintaining glucose homeostasis in synergism with insulin. IGF-1 can directly stimulate glucose transport into the muscle through either IGF-1 or insulin/IGF-1 hybrid receptors. In severely decompensated diabetes including diabetic ketoacidosis, plasma levels of IGF-1 are low and insulin delivery into the portal system is required to normalize IGF-1 synthesis and bioavailability. Normalization of serum IGF-1 correlated with the improvement of glucose homeostasis during insulin therapy providing evidence for the use of IGF-1 as biomarker of metabolic control in diabetes. Taking apart the inherent mitogenic discussion, diabetes treatment using insulins with high affinity for the IGF-1 receptor may act as an endocrine pacer exerting a cardioprotective effect by restoring the right level of IGF-1 in bloodstream and target tissues, whereas insulins with low affinity for the IGF-1 receptor may lack this positive effect. An excessive and indirect stimulation of IGF-1 receptor due to sustained and chronic hyperinsulinemia over the therapeutic level required to overtake acute/chronic insulin resistance may act as endocrine disruptor as it may possibly increase the cardiovascular risk in the short and medium term and mitogenic/proliferative action in the long term. In conclusion, normal IGF-1 may be hypothesized to be a good marker of appropriate insulin treatment of the subject with diabetes and may integrate and make more robust the message coming from HbA1c in terms of prediction of cardiovascular risk.

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Section: Gh/igf-1 Axis In Diabetes Mellitusmentioning

confidence: 99%

Insulin and GH–IGF-I axis: endocrine pacer or endocrine disruptor?

et al. 2014

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“…Spontaneous GH secretion as well as GHRH stimulated GH may be increased, normal or decreased [3]. One of the main determinants of these differences was obesity where obese T2D patients display significantly reduced GH responses to GHRH compared to lean individuals and to non-obese diabetic patients [29, 30]. …”

Section: Gh Response To Oral Glucose and To Chronic Hyperglycemiamentioning

confidence: 99%

Growth Hormone Response to Oral Glucose Load: From Normal to Pathological Conditions

Hage

Kamenický

Chanson³

2019

Neuroendocrinology

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The exact physiological basis of acute growth hormone (GH) suppression by oral glucose is not fully understood. Glucose-mediated increase in hypothalamic somatostatin seems to be the most plausible explanation. Attempts to better understand its underlying mechanisms are compromised by species disparities in the response of GH to glucose load. While in humans, glucose inhibits GH release, the acute elevation of circulating glucose levels in rats has either no effect on GH secretion or may be stimulatory. Likewise, chronic hyperglycemia alters GH release in both humans and rats nonetheless in opposite directions. Several factors influence nadir GH concentrations including, age, gender, body mass index, pubertal age, and the type of assay used. Besides the classical suppressive effects of glucose on GH release, a paradoxical GH increase to oral glucose may be observed in around one third of patients with acromegaly as well as in various other disorders. Though its pathophysiology is poorly characterized, an altered interplay between somatostatin and GH-releasing hormone has been suggested and a link with pituitary ectopic expression of glucose-dependent insulinotropic polypeptide receptor has been recently demonstrated. A better understanding of the dynamics mediating GH response to glucose may allow a more optimal use of the OGTT as a diagnostic tool in various conditions, especially acromegaly.

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“…In one study, GH levels were higher both in the fasting state and in response to glucose load in lean women carrying the Fat Mass and Obesity-Associated (FTO) haplotype and this increase in GH was accompanied with increased glucose, insulin and C-peptide levels (358). On the contrary, another study has found that obese diabetic subjects had slightly decreased GH responses to GHRH and pyridostigmine (an anticholinesterase suppress SST) compared with obese non-diabetic subjects whereas Lean T2DM showed a blunted GH release after GHRH and pyridostigmine compared with normal-weight healthy subjects (96). Thus, it was hypothesized that impaired GH secretion in both lean and obese T2DM…”

Section: Discussionmentioning

confidence: 96%

“…Moreover, it resulted in a decline in fat mass and an increase in lean mass, but showed a reversible decrease in insulin sensitivity (105). Another study has found that both obese and lean diabetic subjects had decreased GH responses to GHRH and pyridostigmine (an acetylcholinesterase inhibitor, stimulates GH release), compared with obese and normal-weight healthy subjects respectively (96). In this study, it was hypothesized that impaired GH secretion in both lean and obese T2DM could be related to the hyperglycaemia and hyperinsulinaemia that affect SST tone independent of BW.…”

Section: Acknowledgementsmentioning

confidence: 99%

Evaluation of Pharmacological Modification of Growth Hormone Secretagogue Receptor in a Mouse Model of Non-Obese Type 2 Diabetes Mellitus

Mosa¹,

Mofeed²

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While it appears that obesity is associated with the higher incidence of type 2 diabetes mellitus (T2DM), recent findings that T2DM affects non-obese people are becoming more noticeable. Many of those who are not obese by traditional weight measurements have an increased percentage of body fat distributed predominately in the abdominal and visceral regions. Disorders of lipid metabolism play a major role in the pathogenesis of this nonobese diabetic phenotype. For examples, lipodystrophic patients develop insulin resistance due to insufficient adipose tissue and aged lean people with diabetes have defects in mitochondrial lipid oxidative mechanisms. Such non-obese diabetic patients are at increased risk of developing cardiovascular (CVD) complications. The management of non-obese T2DM should focus not only on life style modifications or blood glucose control but also strategies for correction of lipid metabolic aberrations. Growth hormone (GH) exerts powerful influences on growth and body composition. In obese animal models and human, GH is known to correlate inversely with insulin concentrations. Some studies suggest that insulin may have a direct inhibitory effect on GH secretion, whereas others showed that insulin inhibits GH secretion via suppression of growth hormone releasing hormone (GHRH) or stimulation of somatostatin (SST). Although GH-insulin relationship is well documented in obesity, studies of this GH-insulin relationship in non-obese diabetes are sparse and contradictory. Thus, this study aimed to investigate the pulsatile GH profile and its regulatory factors in MKR mice which are non-obese diabetic mice generated by igf-1 receptor mutation in skeletal muscle. Our observations demonstrated that unlike obese mice, MKR mice had normal to higher pulsatile GH secretion at different age groups. Nevertheless, there were no detectable changes in gene expressions of hypothalamic GHRH and SST. Interestingly, hypothalamic orexigenic NPY gene expression was increased that might affect GH secretion. These findings suggest that the relationship between GH and insulin was altered in MKR mice, leading to higher GH concentrations despite hyperinsulinaemia. Given that MKR mice exhibited postnatal growth retardation, we anticipated that endogenous GH levels would increase to facilitate rapid linear growth and promote muscle development that assist nutrient uptake and utilization.Therapy using growth hormone secretagogues (GHS) that increase endogenous GH secretion through binding to the ghrelin receptor (GHS-R1a) might have beneficial effects on lipid metabolism with less adverse effects on glucose metabolism than exogenous GH administration. Recent studies have provided some interesting avenues for further exploration on how Hexarelin, one of synthetic peptide GHS, enhanced fat metabolism of white adipose tissue (WAT) via CD36 activation independently of GHS-R1a. To address the effects of Hexarelin in non-obese diabetes, MKR were received daily intraperitoneal (I.P.) injection of Hexarelin (200ug/kg body ...

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Effect of pyridostigmine on the growth hormone response to growth hormone-releasing hormone in lean and obese type II diabetic patients

Cited by 24 publications

References 33 publications

Insulin and GH–IGF-I axis: endocrine pacer or endocrine disruptor?

Insulin and GH–IGF-I axis: endocrine pacer or endocrine disruptor?

Growth Hormone Response to Oral Glucose Load: From Normal to Pathological Conditions

Evaluation of Pharmacological Modification of Growth Hormone Secretagogue Receptor in a Mouse Model of Non-Obese Type 2 Diabetes Mellitus

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