Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of streptozotocin diabetes on the level of growth hormone, growth hormone releasing hormone, and somatostatin mRNA was measured in control rats, in diabetic rats maintained on insulin, and in diabetic rats in which insulin had been withheld for 3 days. Total cytoplasmic RNA samples were prepared from the pituitary and hypothalamic tissues of each animal and analyzed by dot blot or Northern blot hybridization. No significant difference was observed between control and insulin-treated groups with regard to body weight or plasma glucose concentration. The insulin withdrawal group had significantly higher plasma glucose concentrations and lower body weights, confirming diabetic status. There was no significant difference in the level of growth hormone, growth hormone releasing hormone, and somatostatin mRNA among any of the three groups however. We conclude that alterations in the regulation of circulating growth hormone in the streptozotocin-induced diabetic rat, removed from insulin treatment for 3 days, did not occur at the transcriptional or RNA processing level. This conclusion extends to hypothalamic growth hormone releasing hormone, and somatostatin gene expression as well. Regulatory changes in growth hormone level previously noted during insulin withdrawal in the streptozotocin-induced diabetic rat could be the result of post-transcriptional processes operating at the level of hormone synthesis or release.
 ...
PMID:Expression of growth hormone, growth hormone releasing hormone, and somatostatin genes is unperturbed in the streptozotocin-induced diabetic rat. 168 55

Following a standard mixed meal, plasma concentrations of growth hormone releasing hormone (GHRH), somatostatin (SMS) and growth hormone (GH) were measured every 30 min for 300 min in six young adults with type I insulin-dependent diabetes mellitus (IDDM) and five normal controls. Mean blood glucose concentrations were higher and mean free insulin levels lower in the diabetics compared with controls both in fasting specimens and at all times following the mixed meal. Basal concentrations (mean +/- SEM) of GHRH were similar in diabetic (12.7 +/- 1.8 pg/ml) and control subjects (11.8 +/- 1.1 pg/ml). Following ingestion of the mixed meal, a rise in GHRH was observed in the control subjects maximal between 30 and 240 min (P less than 0.025) but the response was blunted in the diabetics. Mean GHRH concentrations were greater in the controls than in the diabetic subjects at all stages during the test, the maximum difference being noted at 120 mins (P less than 0.04). Basal SMS concentrations and those observed after the mixed meal were similar in diabetic and control subjects. These results indicate that glucose and insulin may play a role in the regulation of GHRH release following a mixed meal but circulating levels of GHRH and SMS are unlikely to be relevant to the abnormal regulation of GH in IDDM.
 ...
PMID:The growth hormone releasing hormone (GHRH) response to a mixed meal is blunted in young adults with insulin-dependent diabetes mellitus whereas the somatostatin response is normal. 197 74

Growth hormone levels following an intravenous bolus injection of 1 micrograms/kg body weight growth hormone releasing hormone were measured in 21 non-obese and 26 obese patients with Type 2 (non-insulin-dependent) diabetes mellitus and in 13 control subjects. Growth hormone responses in non-obese Type 2 diabetic patients were not statistically different from control subjects. However, obese Type 2 diabetic patients had significantly decreased growth hormone responses to growth hormone releasing hormone when compared with non-obese Type 2 diabetic patients (p less than 0.02). In 9 Type 2 diabetic patients growth hormone releasing hormone tests were performed both during hyperglycaemia and after metabolic improvement by insulin treatment. Growth hormone responses before and after insulin treatment were not statistically different. Our data demonstrate that growth hormone responses to growth hormone releasing hormone in non-obese Type 2 diabetic patients do not differ significantly from control subjects; obesity blunts growth hormone responses to growth hormone releasing hormone in Type 2 diabetes mellitus; and growth hormone responses following growth hormone releasing hormone administration in Type 2 diabetes mellitus are not influenced by the state of metabolic control.
 ...
PMID:Effect of growth hormone releasing hormone on growth hormone secretion in type 2 (non-insulin-dependent) diabetes mellitus. 310 23

It is well established that the central alpha 2-adrenergic agonist clonidine can enhance growth hormone (GH) secretion in humans. This effect is most likely due to stimulation of hypothalamic growth hormone releasing hormone (GHRH) release. To determine the potency of the new I1-imidazoline receptor agonist moxonidine to release pituitary hormones, 12 normal volunteers received clonidine (0.3 mg), moxonidine (0.3 mg), or placebo orally according to a randomized, double-blind protocol. Blood was drawn prior and up to 180 min after drug administration for determination of GH, adrenocorticotropic hormone (ACTH), prolactin, thyrotropin (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), glucose, clonidine, and moxonidine concentrations. The results were compared to those obtained in a standard GHRH stimulation test (1 microgram/kg i.v.). Serum GH levels increased significantly in response to GHRH, clonidine, and moxonidine. However, the increase was less pronounced in response to clonidine and moxonidine as compared to GHRH (mean +/- SEM): after clonidine, GH increased from 0.2 +/- 0.1 to 5.4 +/- 1.5 ng/ml, p < 0.05; moxonidine increased GH levels from 0.1 +/- 0.04 to 4.8 +/- 1.9 ng/ml (p < 0.05); GHRH caused an increase from 0.01 +/- 0.05 to 14.8 +/- 2.5 ng/ml (p < 0.05). No significant change was observed in the concentration of any other pituitary hormone. We conclude that the new I1-imidazoline receptor agonist moxonidine stimulates GH release to a similar extent as clonidine.
Exp Clin Endocrinol Diabetes 1995
PMID:Growth hormone secretion in response to the new centrally acting antihypertensive agent moxonidine in normal human subjects: comparison to clonidine and GHRH. 758 24

The hypothalamo-pituitary-insulin-like growth factor I (IGF-I) axis was studied in 24 prepubertal children with insulin-dependent diabetes mellitus (IDDM) and 12 non-diabetic children. There were no significant differences between the diabetic and control subjects in basal concentrations of immunoreactive growth hormone releasing hormone (ir-GHRH), growth hormone (GH) or stimulated GH levels, but after exercise ir-GHRH concentrations were higher in the diabetic children. Peripheral IGF-I levels were significantly lower in the diabetic children, and even lower in those with poor metabolic control. A positive correlation was found between IGF-I levels and circulating free insulin concentrations in the diabetic subjects (r = 0.49, p < 0.05). These observations suggest that the GH response to physiological stimulation is normal in prepubertal diabetic children. Exercise-induced GH response may not be mediated by GHRH. IGF-I levels were reduced in prepubertal children with IDDM and even more so in subjects with poor metabolic control. This may be a consequence of transitory hypoinsulineamia, emphasizing the importance of adequate insulinization to facilitate optimal growth in children and adolescents with IDDM.
 ...
PMID:Normal stimulated growth hormone secretion but low peripheral levels of insulin-like growth factor I in prepubertal children with insulin-dependent diabetes mellitus. 767 Feb 47

In a previous paper we demonstrated a link between growth hormone releasing hormone (GHRH) and prostaglandin E2 (PGE2) in their action on growth hormone (GH) in normal subjects. However, in diabetes mellitus various disturbances of GH and PGE2 secretion have been reported. In the present study the response of GH, PGE2 and insulin to GHRH (1 microgram/kg b.w.) intravenously was investigated in 12 poorly controlled non-insulin-dependent diabetic patients (8 males and 4 females) and 10 normal volunteers (5 males and 5 females). After GHRH injection, GH increased in diabetic patients from 2.28 +/- 0.52 mU/l to 14.76 +/- 1.29 mU/l at 30 min (p < 0.001). This response was not statistically different compared to the control subjects. The basal values of plasma PGE2 were significantly lower in diabetic patients than in control subjects. GHRH induced a slight but significant increase of PGE2 in normal subjects (9.80 +/- 0.44 pg/ml at 0 min; 14.50 +/- 1.30 pg/ml at 90 min, p < 0.05) and did not have any effect on PGE2 in diabetic patients. Serum insulin decreased significantly after GHRH in both normal subjects and diabetic patients at 60 min. We conclude that GH response to GHRH is not significantly impaired in poorly controlled non-insulin-dependent diabetic patients. The lack of an effect of GHRH on PGE2 in diabetic subjects provides further evidence of abnormal PGE2 synthesis or metabolism in this disorder. The physiological significance of the GHRH suppressive effect on serum insulin remains to be explained.
 ...
PMID:Effect of growth hormone releasing hormone on growth hormone, prostaglandin E2 and insulin in non-insulin-dependent diabetic patients. 874 Feb 45

Patients with beta-thalassemia often present with abnormalities in growth and other endocrine functions. Growth hormone (GH) secretion is controlled via somatostatin and growth hormone releasing hormone (GHRH). Recently, Hexarelin, a new potent GH secretagogue (His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH2), was synthesized. Our study was designed to assess and compare its efficacy as a GH secretagogue to GHRH 1-29 in beta-thalassemia. Eighteen patients, regularly transfused and chelated, were studied; 11 were short statured. None had diabetes mellitus, hypothyroidism, hypopara-thyroidism or major organ failure. We measured GH at 0, 30, 60, 90, 120 min after GHRH 1-29 or Hexarelin administration. Hexarelin p.o. or i.v. evoked a brisk rise of serum GH which was significantly higher (p < 0.01) than that induced by GHRH 1-29 i.v. In conclusion, Hexarelin has greater GH releasing capacity than GHRH 1-29 at 1 microgram/kg i.v. and can thus be viewed as a potential therapeutic agent in GH deficient states.
 ...
PMID:Growth hormone release by the novel GH releasing peptide hexarelin in patients with homozygous beta-thalassemia. 936 40

1. Regulation of pulsatile secretion of growth hormone (GH) relies on hypothalamic neuronal loops, major transmitters involved in their operation are growth hormone releasing hormone (GHRH) synthetized mostly in arcuate nucleus (ARC) neurons, and somatostatin (SRIH), synthetized both in hypothalamus periventricular (PVe) and ARC neurons. 2. Neurons synthetizing both peptides can inhibit each other in a reciprocal manner. Other neuropeptides synthetized in ARC neurons, such as galanin, or in ARC interneurons, such as neuropeptide Y (NPY), are able to modulate synthesis and release of GHRH and SRIH into the hypothalamohypophyseal portal system. 3. In addition, the hitherto uncharacterized endogenous ligand of the recently cloned growth hormone releasing peptide receptor, expressed mostly in the ARC, triggers GH release, presumably by actions on ARC interneurons. 4. Thyroid, gonadal, and adrenal steroid hormones also affect the GHRH-SRIH balance; a differential distribution of sex steroid receptors in the ARC and the PVe is likely to account for the different pattern of GH secretion in male and female animals. 5. Growth hormone itself is able to inhibit the amplitude of GH secretory episodes and to increase their frequency, by entering the brain (presumably by receptor-mediated internalization at the level of the choroid plexus) and acting subsequently on ARC neurons. 6. At the pituitary level, major neurotransmitters regulating GH cells act on receptors of the VIP/PACAP/GHRH family and of the somatostatin family, in particular, sst2 and sst3. Those are coupled to accumulation of cAMP as a second messenger. 7. In addition, patch-clamp experiments and measurement of intracellular Ca2+ indicate that GH cells present characteristic, GHRH-dependent, but self-maintained Ca2+ spikes and [Ca2+]i transients, which reflect adaptive mechanisms to constraints of episodic release. 8. Recent data on transcription factors affecting GH gene expression and somatotrope differentiation are also summarized. 9. Regulation and differentiation of somatotropes also depend upon paracrine processes within the pituitary itself and involve growth factors and several neuropeptides, for instance, vasoactive intestinal peptide, angiotensin 2, endothelin, and activin. 10. Finally, characteristic changes occur in the GH secretory pattern under discrete, pathological conditions, such as abnormal growth and dwarfism, diabetes, and acromegaly, as well as during inflammatory processes.
 ...
PMID:Hypothalamic and hypophyseal regulation of growth hormone secretion. 952 32

The modern era of growth hormone research began in 1981 with the characterization and synthesis of the primary stimulator of GH synthesis and secretion, growth hormone releasing hormone. Discovery of this peptide and studies in human adults and children resulted in unraveling the complex nature of the regulation of GH secretion. Discovery of regulatory mechanisms has permitted a greater understanding of normal and abnormal growth hormone physiology. The use of growth hormone therapeutically as replacement in GH deficient adults is in its medical infancy, but preliminary studies indicate a beneficial effect on body composition, serum lipid concentrations, bone mineral density, muscle strength, and exercise endurance. These studies over the past decade resulted in Food and Drug Administration approval of GH for replacement in adults with hypothalamic or pituitary disease. It remains to be determined whether or not chronic GH replacement will have beneficial effects on morbidity and mortality. The use of growth hormone in other areas such as aging, catabolic illness, obesity, diabetes, and muscular disorders is under active investigation and risks and benefits remain to be determined.
 ...
PMID:The Gordon Wilson Lecture. Growth hormone replacement in adults and other uses. 960 Nov 30

This review focuses on experiments in humans examining the regulation of the hypothalamo-pituitary-adrenal (HPA) system during nocturnal sleep. The HPA system is a most important mediator of the organism's response to stress. The early phase of nocturnal sleep dominated by extended epochs of slow wave sleep (SWS), is the only time of day in which secretory activity of this axis is subject to a pronounced and persistent inhibition resulting in minimum concentrations of ACTH and cortisol. During late sleep predominated by rapid eye movement (REM) sleep. HPA secretory activity reaches a diurnal maximum. Comparison of the response to administration of exogenous secretagogues of ACTH in men during sleep and nocturnal wakefulness indicated that early sleep, and in particular SWS, is associated with an inhibition of pituitary-adrenocortical responsiveness, which is presumably due to hypothalamic secretion of an as yet unknown release inhibiting factor of ACTH. Pituitary-adrenocortical responsiveness during early sleep was disinhibited after canrenoate which is a selective blocker of mineralocorticoid receptors (MR) located primarily in limbic-hippocampal structures. Hippocampal neuronal networks are known to integrate corticosteroid feedback via both, the MR and the classical glucocorticoid receptor (GR). Prevailing MR related activity in this network seems to act as a trigger for the inhibition of the HPA system. During early sleep, the same hippocampal network appears to be concurrently involved in the formation of declarative memory. Activation of GR after administration of dexamethasone completely blocked the formation of declarative memory during early sleep, indicating that the inhibition of HPA secretory activity is a necessary prerequisite for this memory process. Dysfunction of the described neuro-endocrine mode of regulation during early sleep is present in patients with Cushing's disease, in patients with severe depression and in aged humans. All of these groups show insufficient inhibition of HPA secretory activity particular prominent during early sleep, and reduced SWS in concert with impairments of declarative memory function. First clinical trials suggest that this trias of symptoms may benefit from intranasal treatment with neuropeptides like vasopressin and growth hormone releasing hormone.
Exp Clin Endocrinol Diabetes 1998
PMID:Hypothalamus-pituitary-adrenal activity during human sleep: a coordinating role for the limbic hippocampal system. 971 Mar 53


1 2 Next >>