Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with type 1 diabetes mellitus (IDDM) show augmented GH secretion, which is implicated in the pathogenesis of microvascular complications. On the other hand, it is well known that beta-adrenergic receptors have inhibitory influence on GH secretion, likely via stimulation of hypothalamic somatostatin. Since the possibility of pharmacological suppression of GH secretion would be of value in IDDM, we investigated the effect of salbutamol (SAL, 4 mg orally at -60 min) on the GH response to GHRH (1 micrograms/kg iv at 0 min) in 6 well-controlled (mean HbA1c +/- SEM: 7.3 +/- 0.5%) patients with IDDM. Salbutamol was able to inhibit basal GH levels (p < 0.05) as well as to abolish the GHRH-induced GH rise. After SAL administration, a significant (p < 0.05) reduction of glucagon levels was also found. Our data show that the enhancement of beta 2 adrenergic activity by oral therapeutical doses of SAL inhibits basal and GHRH-stimulated GH secretion in patients with IDDM.
 ...
PMID:Inhibition by salbutamol of GHRH-induced GH release in type 1 diabetes mellitus. 133 41

Conflicting data are found in the literature concerning the growth hormone response to growth hormone-releasing hormone and the insulin-like growth factor I level in Type I diabetes mellitus. The GH response to GHRH and the serum IGF-I level were studied in 29 moderately to well regulated male diabetic patients and 20 age-matched controls. The mean fasting glucose and HbA1c (normal less than 6.5%) levels were, respectively: 10.2 +/- 0.8 mmol/l and 7.1 +/- 0.2%, and 4.1 +/- 0.1 mmol/l and 5.4 +/- 0.1% (mean +/- SEM). The GH response to GHRH was higher in the diabetic patients at 15, 30 and 45 min (p less than 0.05), and also delta peak GH was higher compared with controls: 34.8 +/- 5.6 vs 18.0 +/- 2.4 micrograms/l (p less than 0.02). The serum IGF-I level was lower in the diabetic patients: 460 +/- 30 vs 700 +/- 60 U/l (p less than 0.01). No correlations could be demonstrated between delta peak GH, serum IGF-I or HbA1c level. When only patients with a mean fasting glucose less than or equal to 7.0 mmol/l and normal HbA1c (5.8 +/- 0.3%) were analysed, delta peak GH was also elevated compared with controls: 47.0 +/- 16.3 vs 18.0 +/- 2.4 micrograms/l (p less than 0.02). No difference was observed in GH response or serum IGF-I level in 5 patients with (pre)proliferative retinopathy compared with patients without this complication. It is concluded that in Type I diabetes the GH response to GHRH is increased, even in well regulated patients, and that the serum IGF-I level is depressed.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Growth hormone in type I diabetic and healthy man. 211 Apr 12

It is well known that muscarinic cholinergic blockade either reduces or abolishes stimulated GH release in normal subjects. In this study we have investigated whether cholinergic muscarinic blockade could reduce the GH responses to GRF 1-29 and TRH in acromegalic subjects. Eight acromegalic subjects underwent two GRF tests (GRF 1-29, 1 microgram/kg i.v.) with and without pirenzepine (0.6 mg/kg, i.v.). A further four of these patients received TRH (200 micrograms/kg, i.v.) on separate occasions with and without pirenzepine (0.6 mg/kg, i.v.). Cholinergic muscarinic blockade did not alter the GH responses to GRF and TRH in patients with acromegaly. These findings are in contrast with previous data reported on the effects of cholinergic blockade on stimulated GH levels in normal subjects and in patients with type I diabetes mellitus and are compatible with the view that somatotroph adenomas are functionally disconnected from hypothalamic control mechanisms.
 ...
PMID:Lack of effect of muscarinic cholinergic blockade on the GH responses to GRF 1-29 and TRH in acromegalic subjects. 287 6

In 10 patients with type I diabetes mellitus, 9 acromegalic patients, and 8 normal subjects, serum GH levels after an iv injection of 1 microgram/kg BW human GH-releasing hormone-(1-44) (GHRH) with and without cholinergic muscarinic receptor blockade (1 mg atropine, im, 15 min before GHRH) were measured. The GH increase after GHRH treatment in type I diabetic patients did not differ significantly from that in normal subjects. Pretreatment with atropine almost completely blocked the GH response to GHRH in patients with type I diabetes and normal subjects, but did not suppress the GH response to GHRH in acromegalic patients. These data indicate that cholinergic muscarinic receptors modulate GH secretion in normal man as well as in patients with type I diabetes mellitus, whereas acromegalic patients have a defect of cholinergic control of GH secretion.
 ...
PMID:Effect of cholinergic muscarinic receptor blockade on human growth hormone (GH)-releasing hormone-(1-44)-induced GH secretion in acromegaly and type I diabetes mellitus. 308 23

Large doses of pirenzepine given at bedtime suppress nocturnal GH secretion and abolish dawn phenomenon. As GH suppression may be beneficial in diabetic subjects we have investigated the effect of routine doses of pirenzepine on GH secretion in 9 type 1 diabetics. In the acute study pirenzepine 20 mg i.v. administered 15 min before GHRH 80 micrograms i.v. completely inhibited GHRH-induced GH response and the peak GH values were reduced from 66.3 to 9.2 ng/ml, P < 0.005. In the chronic study pirenzepine was given in a daily dose of 75 or 150 mg for 4 days and GH was measured hourly during 24-h study before and on the fourth day of pirenzepine administration. GH secretion calculated as area under curve (AUC) was not affected by pirenzepine and the values of AUC were: 139 ng/ml per h (the control 24-h study) and 123 ng/ml per h (pirenzepine 75 mg) and 303 ng/ml per h (pirenzepine 150 mg). Mean plasma glucose was not changed by pirenzepine. GH secretion calculated as AUC and mean 24-h GH level did not correlate with metabolic control of diabetes assessed by HbA1. It is concluded that routine doses of pirenzepine do not suppress GH hypersecretion in type 1 diabetic subjects and therefore this agent does not seem suitable for the purpose of 24-h GH suppression in type 1 diabetes mellitus.
 ...
PMID:Short term pirenzepine treatment is ineffective in suppressing 24-h growth hormone secretion in type 1 diabetes mellitus. 831 19

GH hypersecretion in insulin-dependent diabetes (IDDM) is well documented. Although it has recently been shown that residual insulin secretion determines the magnitude of this GH hypersecretion, the underlying mechanisms of the disorder have not yet been clarified. The 24-h GH and blood glucose profiles, insulin-like growth factor I (IGF-I) concentrations and GH responses to GRF were analyzed in 21 insulin-dependent diabetics and 4 healthy subjects before and after 7 days treatment with recombinant human GH (rhGH) (4 IU given sc at 0800 h). According to C-peptide response to glucagon IDDM patients were subdivided into C-peptide negative (CpN, n = 12) patients without endogenous pancreatic beta-cell activity and C-peptide positive (CpP, (n = 9) patients with endogenous insulin secretion. No significant difference could be observed between the mean 24-h blood glucose profile before and after rhGH treatment in any treated group. Before and on rhGH treatment the highest 24-h GH values were observed in CpN patients when compared to CpP and controls. The rhGH treatment induced a similar increase in the mean 24-h GH concentrations in all groups studied which was statistically significant only in CpP diabetics. Mean pretreatment serum IGF-I concentrations were not significantly different between CpN, CpP patients and controls. The net increase in IGF-I concentrations after rhGH treatment was however, significantly lower in CpN patients than in CpP and control subjects. GRF-induced GH response before and after rhGH treatment was significantly greater in diabetics than in controls. The response of GH to GRF in CpN diabetics was however, almost unchanged after treatment whereas it became lower in CpP diabetics and controls. The dose of 4 IU of rhGH increased significantly GH levels in diabetics with preserved beta-cell function with consequent increase in IGF-I levels and attenuation of GRF induced GH response. In contrast, the same dose of rhGH failed to induce significant increase in GH levels in diabetics without residual beta-cell activity, most probably due to already high pretreatment levels. In addition, neither increase in IGF-I levels nor suppression of GH response to GRF on rhGH treatment was observed in CpN diabetics. The results are in keeping with an important role of portal insulin in GH-induced hepatic IGF-I secretion.
 ...
PMID:The effect of recombinant human growth hormone on regulation of growth hormone secretion and blood glucose in insulin-dependent diabetes. 832 51

Enhanced GH secretion and hyperglycemia are suggested to play a role in the pathogenesis of glomerular hyperfiltration in insulin dependent diabetes mellitus. In this study we measured the GH response to GHRH (1 microgram/kg body weight), metabolic control, and renal function in 44 patients in order to explore a possible association between these parameters. Hyperfiltration [glomerular filtration rate (GFR) > 130 ml/min/1.73 m2] was present in 21 patients and normofiltration in 23. The duration of diabetes, plasma concentrations of renin, catecholamines, insulin-like growth factor-1 and blood glucose during renal function measurements were not different. GH response was significantly higher in patients with hyperfiltration. There was a positive relation between GH response and GFR (r = 0.51, P < 0.001) and effective renal plasma flow (r = 0.39, P < 0.01). GFR was correlated with insulin dose (r = 0.48, P < 0.001). There was no difference in glycosylated hemoglobin between the two groups. Patients with hyperfiltration used more insulin, had more frequent blood glucose values below the threshold level for activation of GH secretion, and had greater glycemic excursions than patients with normofiltration. The results suggest that GH hypersecretion and glomerular hyperfiltration are related and they support the possibility of a linkage between GH hypersecretion and glucose variability.
 ...
PMID:Glomerular hyperfiltration in insulin-dependent diabetes mellitus is correlated with enhanced growth hormone secretion. 834 58

In insulin dependent diabetes mellitus (IDDM) either elevated growth hormone (GH) levels or abnormal responses to specific as well as unspecific stimuli have been reported. As hyperglycemia is known to blunt GH response to various stimuli, a normal GH response to GHRH in presence of hyperglycemia should also be considered inappropriate. To investigate the mechanism underlying this inappropriate GH response, in 9 patients with IDDM, selected for normal GH response to GHRH, we studied the GH response to two consecutive GHRH boluses (1 microgram/kg), the second of which preceded 30 min before by pyridostigmine (120 mg p.o.). Seven age matched normal volunteers were evaluated as control group. Basal plasma glucose and serum GH levels were significantly higher in patients with IDDM than in normal subjects (184.4 +/- 9.6 vs 86.2 +/- 4.4 mg/dl, p < 0.01 and 2.4 +/- 1.0 vs 1.0 +/- 0.4 microgram/l, p < 0.01 respectively). Both in normal subjects and in patients with IDDM the GH response to the second consecutive GHRH administration was lower than that of the first GHRH bolus (delta AUC: 82.5 +/- 28.3 vs 401.1 +/- 131.2 micrograms/l/h, p < 0.05 and 77.2 +/- 30.4 vs 336.8 +/- 60.0 p < 0.02, respectively). Pyridostigmine was able to restore the blunted GH responsiveness to the second GHRH administration in both groups, but this response was found higher in normal than in diabetic subjects (delta AUC: 1250.8 +/- 136.2 vs 527.5 +/- 147.6, p < 0.01). Since the GH-releasing effect of PD is likely to be mediated by the inhibition of hypothalamic somatostatin release, our results suggest that there is also an impaired somatostatin tone in hyperglycemic type 1 diabetic patients with normal GH response to GHRH.
 ...
PMID:Repeated administration of growth hormone-releasing hormone with or without previous administration of pyridostigmine in insulin-dependent diabetes mellitus. 917 28

In type 1 diabetes mellitus (DM 1), high GH basal levels and exaggerated GH responses to several stimuli, including GHRH, have been described. GH-releasing peptide-6 (GHRP-6) is a synthetic hexapeptide that specifically stimulates GH release, both in vitro and in vivo. The aim of this study was to evaluate the effects of GHRP-6 alone or in combination with GHRH on GH secretion in DM 1. Six type 1 diabetic males and six age-, sex-, and body mass index-matched control volunteers were studied. Each subject received GHRH (100 microg iv), GHRP-6 (90 microg iv), and GHRH plus GHRP-6 on three separate days. GH peak values were higher in DM 1 patients than in control volunteers, after GHRH (52.2+/-9.8 vs. 19.3+/-6.0 microg/L; P = 0.016), GHRP-6 (66.2+/-9.6 vs. 39.9+/-6.3 microg/L; P = 0.05), and GHRH plus GHRP-6 (81.8+/-4.4 vs. 53.7+/-8.2 microg/L; P = 0.01). An additive GH response to combined administration of these two peptides was observed in diabetic patients. Serum insulin-like growth factor (IGF)-1 levels were diminished in DM 1, with respect to normal subjects (145.2+/-21.5 vs. 269.7+/-42.0 microg/L; P = 0.01), whereas IGF-binding protein-3 levels were not significantly different between DM-1 and controls. In summary, GHRP-6 is a potent stimulus for GH secretion in DM 1. The combined administration of GHRP-6 plus GHRH constitutes the most powerful stimulus for GH secretion in DM 1. These patients exhibit a greater GH secretory capacity than normal subjects, probably caused by a diminished tone in the IGF-1 sustained negative feedback control exerted upon somatotroph responsiveness.
 ...
PMID:Growth hormone (GH) response to GH-releasing peptide-6 in type 1 diabetic patients with exaggerated GH-releasing hormone-stimulated GH secretion. 976 81

In vitro data have recently suggested that sulfonylureas (SUs) enhance GH secretion by modulating the effects of GHRH and somatostatin in pituitary cells. The present study was undertaken to explore in more detail a possible influence of a single dose of SU (glibenclamide) and a non-SU (repaglinide) insulin secretagogue on circulating GH dynamics. Ten C-peptide-negative type 1 diabetic individuals were examined on three occasions in random order. Either glibenclamide (10.5 mg), repaglinide (8 mg), or placebo was administered after overnight normalization of plasma glucose by iv insulin infusion. Subsequently, GH concentrations were measured regularly after stimulation with GHRH (bolus 0.1 micro g/kg) alone and during concomitant infusion with somatostatin (7 ng.kg(-1).min(-1)). Insulin was replaced at baseline levels (0.25 mU.kg(-1).min(-1)) and plasma glucose clamped at 5-6 mmol/liter. Overall, there were no significant statistical differences in GH responses determined as either GH peak concentrations, integrated levels of GH, or secretory burst mass of GH during the experimental protocol. In contrast, plasma glucagon concentrations were significantly increased during glibenclamide and repaglinide exposure. The present experimental design does not support the hypothesis that acute administration of pharmacological doses of the oral antihyperglycemic agents glibenclamide and repaglinide per se enhance GH release in humans. Additionally, this study shows that these potassium channel inhibitors seem to stimulate glucagon secretion in people who have severe intraislet insulin deficiency (e.g. type 1 diabetes). However, extrapolation of our findings to type 2 diabetic individuals should be done with some caution.
 ...
PMID:The insulin secretagogues glibenclamide and repaglinide do not influence growth hormone secretion in humans but stimulate glucagon secretion during profound insulin deficiency. 1471 64


1 2 Next >>