Biomedical subjects

S Grottoli

Publications and source records attributed to S Grottoli.

At least 55 records · Page 3Linked to original sources

PubMed1999

Effects of alprazolam, a benzodiazepine, on the ACTH-, GH- and PRL-releasing activity of hexarelin, a synthetic peptidyl GH secretagogue (GHS), in patients with simple obesity and in patients with Cushing's disease.

GH secretagogues (GHS) possess potent GH-releasing activity but also stimulate PRL, ACTH and cortisol (F) secretion. To further clarify the endocrine activities of GHS, in 9 obese patients, 9 patients with Cushing's disease and 14 controls we studied the ACTH, F, GH and PRL responses to hexarelin (HEX, 2.0 micrograms/kg i.v.), a peptidyl GHS, alone and preceeded by alprazolam (ALP, 0.02 mg/kg p.o.), a benzodiazepine. The HEX-induced ACTH response in controls was similar to that in obese patients (delta peak: 9.9 +/- 1.9 and 24.7 +/- 7.6 ng/L, respectively) and both were lower (p < 0.002) than that in Cushing's patients (peak: 210.7 +/- 58.4 ng/L). The GH response to HEX in controls (peak: 58.1 +/- 10.3 x g/L) was higher (p < 0.001) than those in obese and Cushing's patients (18.2 +/- 3.8 and 12.6 +/- 5.4 x g/L, respectively) which, in turn, were similar. The PRL responses to HEX in controls, obese and Cushing's patients (peak: 11.9 +/- 1.6, 18.0 +/- 4.5 and 12.4 +/- 1.4 x g/L, respectively) were similar. In controls the HEX-induced ACTH response was abolished by ALP (peak: 8.6 +/- 2.4 vs 28.0 +/- 6.7 ng/L, p < 0.03) which, on the other hand, only blunted that in obese (peak: 12.7 +/- 2.1 vs 42.4 +/- 8.4 ng/L, p < 0.02) and did not modify that in Cushing's patients (205.6 +/- 55.4 vs 175.9 +/- 47.6 ng/L). ALP blunted the GH response to HEX in controls (peak: 31.0 +/- 7.1 x g/L, p < 0.03) while did not modify those in obese and in Cushing's patients (14.5 +/- 5.3 and 13.3 +/- 11.1 x g/L, respectively). ALP did not modify the HEX-induced PRL response in controls, obese and Cushing's patients (peak: 13.8 +/- 0.9, 16.3 +/- 2.4 and 19.2 +/- 1.1 x g/L, respectively). In conclusion, alprazolam inhibits the ACTH response to hexarelin in normal and obese subjects while fails to modify the exaggerated ACTH response in Cushing's Disease suggesting that GHS activate the HPA axis via the hypothalamus in normal and obese subjects but not in patients with Cushing's disease. Alprazolam is also able to blunt the GH-releasing activity of hexarelin in normal subjects but not the low GH response to the hexapeptide in obese and Cushing's patients. The PRL-releasing activity of hexarelin in controls, obese and hypercortisolemic patients is similar and is not modified by alprazolam pretreatment.

Adrenocorticotropic Hormone↗

PubMed1999

Relationships between IGF-I and age, gender, body mass, fat distribution, metabolic and hormonal variables in obese patients.

OBJECTIVE: To compare insulin-like growth factor-I (IGF-I) concentrations in obese and normal subjects, and evaluate the possible relationships between IGF-I concentrations and demographic, anthropometric, metabolic and hormonal variables in obese patients. SUBJECTS AND METHODS: 286 obese outpatients (OB, 234 female and 52 male; age 18-71 y, body mass index (BMI) > 27 kg/m2) were recruited. MEASUREMENTS: BMI, waist-to-hip ratio (WHR), serum basal and oral glucose tolerance test (OGTT)-stimulated glucose and insulin concentrations, IGF-I, basal growth hormone (GH), prolactin (PRL), androgens, thyrotropin (TSH), free triiodothyronine (fT3), free thyroxine (fT4), free fatty acids (FFA), triglycerides, total and high density lipoprotein (HDL)-cholesterol, 24h-urinary cortisol levels and blood pressure (BP) values were measured. IGF-I concentrations were also evaluated in a large population of 326 age-matched controls (controls, 228 women, 98 men; age 20-86 y, BMI < 25 kg/m2). RESULTS: IGF-I concentrations were lower in OB than in controls (age-adjusted mean: 21.6 vs 23.6 nmol/L, P < 0.03). However, individual IGF-I concentrations in OB were within the age-adjusted normal range. In both groups, IGF-I concentrations were gender-independent, and showed a simple negative correlation with age (r = -0.47). In OB, univariate analysis also shows that IGF-I concentrations were negatively correlated with BMI (r = -0.33), but not WHR, with both basal (r = -0.16) and OGTT-stimulated glucose levels (r = -0.17), as well as FFA levels (r = -0.19), and with both diastolic and systolic BP (both r = -0.17). In OB women, IGF-I concentrations positively correlated with PRL (r = 0.31), testosterone (r = 0.30), androstenedione (r = 0.30), and dehydroepiandrosterone-sulfate (DHEAS) concentrations (r = 0.41). No correlation was found with other variables. The multiple regression analysis showed that IGF-I concentrations were inversely and independently related to age and BMI only. CONCLUSIONS: In obesity, IGF-I concentrations are slightly reduced, but generally within the age-adjusted normal range. IGF-I concentrations in obesity show independent and negative relationships with age and BMI, but are not associated with fat distribution, insulin secretion, glucose tolerance, BP or risk indices for cardiovascular disease (CVD).

Adipose Tissue↗

PubMed1999

Relationships between dehydroepiandrosterone-sulphate and anthropometric, metabolic and hormonal variables in a large cohort of obese women.

OBJECTIVE: The aim of the present study was to measure dehydroepiandrosterone-sulphate (DHEA-S) levels in obesity and assess the relationships between DHEA-S and anthropometric, metabolic and hormonal variables. SUBJECTS AND METHODS: We evaluated the serum DHEA-S levels in 217 obese but otherwise normal female subjects (age (mean +/- SEM): 39.4 +/- 0.9, range 18-67 years, body mass index (BMI) = 36.1 +/- 0.4, range 27.1-57.1 kg/m2). RESULTS: DHEA-S levels showed an age-dependent fall similar to that observed in normal women (n = 156, age 46.2 +/- 1.2, range 22-69 years, BMI < 25 kg/m2). Adjusting for age, obese women had mean DHEA-S levels higher than the control group (P < 0.02). In obese patients, DHEA-S levels were directly associated with serum testosterone, androstendione, IGF-I, fT3 levels and 24 h-urinary cortisol. On the other hand, DHEA-S levels were negatively associated with age, total cholesterol, triglycerides levels and systolic blood pressure. No correlation was found with BMI, waist:hip ratio, basal and post-OGTT insulin and glucose, free fatty acids, GH, PRL, fT4, TSH, SHBG levels or diastolic blood pressure. Multiple regression analysis indicated that in obese women, DHEA-S levels were associated negatively to age and positively to testosterone, androstendione and IGF-I levels and daily urinary cortisol. In a subgroup of 20 obese women, DHEA-S levels significantly (P < 0.001) fell after OGTT without any correlation with the insulin response. CONCLUSIONS: The present results show that dehydroepiandrosterone-sulphate levels are not reduced in obesity, being slightly increased, particularly in young adulthood. Dehydroepiandrosterone-sulphate levels are positively and independently associated with androgen, 24-h urinary cortisol and IGF-I levels but do not seem associated with insulin levels or cardiovascular risk indices.

Adolescent↗

PubMed1999

IGF-1 levels in different conditions of low somatotrope secretion in adulthood: obesity in comparison with GH deficiency.

BACKGROUND: It is widely accepted that IGF-I synthesis and release depend on GH secretion as well as on the nutritional status and vary with age. Based on these premises, after the definition of normal IGF-I levels during lifespan, in a large population of normal subjects of both sexes, our aim was to verify IGF-I levels in large groups of adult patients with GH deficiency or obesity, a condition in which a reduced somatotrope secretion is well known. METHODS: To this goal, IGF-I levels were assayed after acid-ethanol extraction, in 326 normal subjects (NS, 98 men and 228 women, age 20-80 yrs, BMI 17.9-26.1 kg/m2), 54 patients with GH deficiency (GHD, 24 men and 30 women, age 20-80 yrs, BMI 18.2-27.1 kg/m2), and 195 patients with obesity (OB, 33 men and 162 women, age 17-71 yrs, BMI 27.7-64.9 kg/m2). In NS, IGF-I levels were similar in both sexes and showed a progressive decrease with age. No correlation was present between IGF-I and BMI in NS. Median IGF-I levels and the 3rd centile in NS when considered per decade were: III) 230 and 108.6; IV) 220 and 129.8; V) 150.5 and 72.4; VI) 163.0 and 62.4; VII) 110 and 41.6; VIII) 82 and 24.7 micrograms/l. In GHD, IGF-I levels were independent on sex and did not show reduction during lifespan. Mean IGF-I levels in GHD were lower than that in NS (64.5 +/- 5.9 vs 171.3 +/- 4.8 micrograms/l, p < 0.01) and did not correlate with age or BMI. Analyzing individual IGF-I levels, in GHD, in the III and IV decade 21/24 patients had IGF-I levels lower than 3rd centile while, up to the VIII decade, only 10/30 had IGF-I levels below normal limits. In OB, IGF-I levels were independent on sex but, like in NS, showed a progressive decrease with age and were independently, negatively correlated with BMI but not with WHR. Analyzing individual IGF-I levels, in OB, IGF-I levels were below 3rd centile in 10/77 patients in the III and IV decade and in only 8/108 patients up to the VIII decade. Mean IGF-I levels in the whole OB population (179.6 +/- 5.9 micrograms/l) were higher (p < 0.01) than those in GHD (64.5 +/- 5.9 micrograms/l) while only in the IV decade IGF-I levels in OB group were lower (p < 0.02) than those in NS (184.7 +/- 12.6 micrograms/l vs 224.0 +/- 9.2 micrograms/l). CONCLUSIONS: In conclusion, present data confirm that IGF-I levels depends on GH secretion as well as on nutritional status, being negatively and independently correlated with age and BMI. IGF-I assay is not a reliable test for the diagnosis of GH deficiency in adulthood though it gives good discrimination between GHD and normal subjects up to 40 yrs of age. In spite of low GH secretion, IGF-I levels are only slightly reduced in obesity, probably as consequence of hyperinsulinism.

Adult↗

PubMed1998

Effects of 3-month nifedipine treatment on endocrine-metabolic parameters in patients with abdominal obesity and mild hypertension.

It is widely accepted that abdominal obesity presents with exaggerated insulin secretion, insulin resistance and a trend toward glucose intolerance. Hypertension is frequently associated to abdominal obesity, and hyperinsulinism could play a role in its pathogenesis. Some studies reported that Ca-antagonists positively influence insulin sensitivity and glucose tolerance in obese patients with normal or elevated blood pressure. However, other studies reported worsening of metabolic balance during treatment with Ca-antagonists in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) patients and in normal subjects. We studied 19 patients with abdominal obesity, mild hypertension and insulin resistance on balanced, mild hypocaloric diet (1400 Kcal), to verify the effects of the Ca-antagonist nifedipine on both basal and oral glucose tolerance test (OGTT)-induced glucose and insulin levels as well as on IGF-I basal and DHEA-S levels and fat mass (FM). To achieve this goal, 10 hypertensive obese subjects (HOB-NIFE, 3 males, 7 females, mean age +/- SD 44.6 +/- 1.7 yr; body mass index (BMI) 37.1 +/- 2.5 Kg/m2, WHR 0.95 +/- 0.02) received 3-month treatment with nifedipine (Adalat Crono 30 Bayer, 1 tab daily) while other 9 hypertensive obese (HOB, 3 males, 6 females, 42 +/- 2.4 yr, BMI 35.8 +/- 1.8 Kg/m2, WHR 0.91 +/- 0.03) were studied during diet only. The same parameters were studied also in 8 normotensive obese patients (OB: 3 males, 5 females, 48.1 +/- 2.1 yr, BMI 35.8 +/- 2.4 Kg/m2, WHR 0.90 +/- 0.03) on the same balanced hypocaloric diet. Basal systolic (SBP) and diastolic (DBP) blood pressure levels in HOB-NIFE and HOB were similar. At baseline, all groups had similar basal and OGTT-induced glucose, insulin and glucose insulin ratio (GIR) levels as well as IGF-I and DHEA-S levels. After 3 months BMI fell to the same extent in all groups (p < 0.05 vs baseline) while WHR and FFM/FM ratio did not change. SBP and DBP decreased HOB-NIFE (p < 0.02) but also during diet alone in both HOB and OB, though to a lesser extent (p < 0.05). Both basal and OGTT-stimulated glucose and insulin levels as well as IGF-I and DHEA-S levels were not modified in HOB-NIFE as well as in HOB and OB. In conclusion, our data indicate that nifedipine treatment does not modify glucose tolerance as well as insulin secretion and sensitivity, IGF-I and DHEA-S levels in hypertensive abdominal obese patients. Thus, nifedipine treatment has no detrimental effects on endocrine-metabolic balance in hypertensive obese patients.

Adult↗

PubMed1998

GH response to GHRH combined with pyridostigmine or arginine in different conditions of low somatotrope secretion in adulthood: obesity and Cushing's syndrome in comparison with hypopituitarism.

BACKGROUND: Diagnosing GH deficiency in adults is difficult due to the age-related variations of GH/IGF-I axis and the influence of nutrition. Nowadays, GH replacement is allowed for patients with GH peak to provocative stimuli < 3 micrograms/L. Somatotrope insufficiency is present in hypopituitarism but also in obesity and hypercortisolism. However, to evaluate GH insufficiency in adults is difficult due to variations of GH and IGF-I levels as function of age and nutrition status. METHODS: We aimed to verify the GH response to GHRH (1 microgram/kg i.v.) combined with pyridostigmine (PD, 120 mg p.o.) or arginine (ARG, 0.5 g/kg i.v.), in 26 hypopituitaric patients (GHD), in 11 obese women (OB), in 8 women with Cushing's syndrome (CS), and in 72 control subjects (NS). RESULTS: IGF-l levels in GHD were lower than those in OB (p < 0.01) and in CS (p < 0.01) which, in turn, were lower to those in NS (p < 0.02). In NS, the GH peak responses to GHRH + PD and GHRH + ARG were similar and the minimum normal GH peak was 16.5 micrograms/L. GHD had GH responses similar, lower than those in NS (p < 0.01) and always below the normal limit. However, only 12/20 and 8/14 had peaks < 3 micrograms/L; conventionally, below this limit severe GH deficiency is shown and rhGH replacement is allowed. In OB, the GH responses to GHRH + PD and GHRH + ARG were similar, lower (p < 0.01) and higher (p < 0.01) than those in NS and GHD, respectively. Six out of 11 OB had GH peaks below the normal limits but nobody < 3 micrograms/L. In CS the GH response to GHRH + PD was lower than that to GHRH + ARG (p < 0.01); both these responses were lower than those in NS (p < 0.01) and even in OB (p < 0.01) but higher than those in GHD (p < 0.01). All and 7/8 CS had GH peaks lower than normal limits after PD + GHRH and ARG + GHRH, respectively while 6/8 showed GH peak < 3 micrograms/L after PD + GHRH but only 1 after ARG + GHRH. CONCLUSIONS: Present data demonstrate that the maximal somatotrope secretory capacity is reduced in OB and even more in CS. From a diagnostic point of view, PD + GHRH and ARG + GHRH tests distinguish OB from severe GHD. As hypercortisolism impairs the activity of cholinesterase inhibitors, only ARG + GHRH, but not PD + GHRH is a reliable test to explore the maximal somatotrope secretory capacity in CS. Notably, even with the ARG + GHRH test, in CS the maximal somatotrope secretory capacity is sometimes so reduced as to overlap with that of severe GHD.

Adult↗

PubMed1998

IGF-I levels in different conditions of low somatotrope secretion in adulthood: obesity in comparison with GH deficiency.

BACKGROUND: It is widely accepted that IGF-I synthesis and release depend on GH secretion as well as on the nutritional status and vary with age. Based on these premises, after the definition of normal IGF-I levels during lifespan, in a large population of normal subjects of both sexes, our aim was to verify IGF-I levels in large groups of adult patients with GH deficiency or obesity, a condition in which a reduced somatotrope secretion is well known. METHODS: To this goal, IGF-I levels were assayed after acidethanol extraction, in 326 normal subjects (NS, 98 men and 228 women, age 20-80 yrs, BMI 17.9-26.1 kg/m2), 54 patients with GH deficiency (GHD), 24 men and 30 women, age 20-80 yrs, BMI 18.2-27.1 kg/m2), and 195 patients with obesity (OB, 33 men and 162 women, age 17-71 yrs, BMI 27.7-64.9 kg/m2). In NS, IGF-I levels were similar in both sexes and showed a progressive decrease with age. No correlation was present between IGF-I and BMI in NS. Median IGF-I levels and the 3rd centile in NS when considered per decade were: III) 230 and 108.6; IV) 220 and 129.8; V) 150.5 and 72.4; VI) 163.0 and 62.4; VII) 110 and 41.6; VIII) 82 and 24.7 microgram/l. In GHD, IGF-I levels were independent on sex and did not show reduction during lifespan. Mean IGF-I levels in GHD were lower than that in NS (64 +/- 5.9 vs 171.3 +/- 4.8 microgram/l, p < 0.01) and did not correlate with age or BMI. Analyzing individual IGF-I levels, in GHD, in the III and IV decade 21/24 patients had IGF-I levels lower than 3rd centile while, up to the VIII decade, only 10/30 had IGF-I levels below normal limits. In OB, IGF-I levels were independent on sex but, like in NS, showed a progressive decrease with age and were independently, negatively correlated with BMI but not with WHR. Analyzing individual IGF-I levels, in OB, IGF-I levels were below 3rd centile in 10/77 patients in the III and IV decade and in only 8/108 patients up to the VIII decade. Mean IGF-I levels in the whole OB population (179.6 +/- 5.9 microgram/l) were higher (p < 0.01) than those in GHD (64.5 +/- 5.9 microgram/l) while only in the IV decade IGF-I levels in OB group were lower (p < 0.02) than those in NS (184.7 +/- 12.6 microgram/l vs 224.0 +/- 9.2 microgram/l). CONCLUSIONS: In conclusion, present data confirm that IGF-I levels depends on GH secretion as well as on nutritional status, being negatively and independently correlated with age and BMI. IGF-I assay is not a reliable test for the diagnosis of GH deficiency in adulthood though it gives good discrimination between GHD and normal subjects up to 40 yrs of age. In spite of low GH secretion, IGF-I levels are only slightly reduced in obesity, probably as consequence of hyperinsulinism.

Adolescent↗

PubMed1997

Reduction of the somatotrope responsiveness to GHRH and Hexarelin but not to arginine plus GHRH in hyperprolactinemic patients.

Aim of the present study was to verify the maximal secretory capacity of somatotrope cells in patients with pathological hyperprolactinemia (HPRL) comparing it with that in normal age-matched women (NW). To this goal in 12 HPRL normal weight patients (age 28.6 +/- 2.6 yr, BMI 23.1 +/- 1.1 kg/m2) and 8 NW (27.2 +/- 0.8 yr, 22.8 +/- 0.8 kg/m2) we studied the GH response to GHRH (1 microgram/kg i.v.), GHRH plus arginine (ARG, 0.5 g/kg i.v.), an amino acid probably acting at the hypothalamic level inhibiting somatostatin release, and Hexarelin (HEX, 2 micrograms/kg i.v.), a synthetic hexapeptide belonging to GHRP family, which acts concomitantly at the pituitary and the hypothalamic level. IGF-I levels in HPRL were similar to those in NW (179.2 +/- 16.5 micrograms/l and 218.5 +/- 30.8 micrograms/l). In NW the GH response to GHRH (AUC: 1299.5 +/- 186.9 micrograms 90 min/l) was lower (p < 0.02) than those to GHRH + ARG (5252.7 +/- 846.3 micrograms 90 min/l) and HEX 3216.6 +/- 462.3 micrograms 90 min/l) which, in turn, were similar. In HPRL the GH response to GHRH (894.7 +/- 242.4 micrograms 90 min/l) was lower (p < 0.03) than that to HEX (1586.5 +/- 251.3 micrograms 90 min/l) and both were lower (p < 0.03) than that to GHRH + ARG (4468.8 +/- 941.7 micrograms 90 min/l). In HPRL the GH responses to GHRH and HEX were lower than those that in NW (p < 0.03) while that to GHRH + ARG was similar in both groups. These results demonstrate that the somatotrope responsiveness to GHRH and HEX is clearly reduced in patients with pathological hyperprolactinemia. On the other hand, in this condition the GH response to GHRH + ARG is normal. As arginine likely acts via inhibition of hypothalamic somatostatin release, these findings show that the maximal secretory capacity of somatotrope cells in hyperprolactinemia is preserved and indicate that partial refractoriness of somatotrope cells to GHRH and HEX could be due to somatostatinergic hyperactivity.

Adenoma↗

PubMed1997

The inhibitory effect of glucose on growth hormone secretion is lost in obesity but not in hypertension.

In obesity there is a clear reduction of both spontaneous and stimulated GH secretion. Furthermore, in obese patients the somatotrope responsiveness to provocative stimulation is selectively refractory to the inhibitory effect of glucose load. It has been hypothesized that hyperinsulinism of obese patients could play a role in the pathogenesis of these alterations. Aim of the present study was to verify the GH response to GHRH and the ability of glucose load to inhibit it in patients with essential hypertension in whom hyperinsulinism and insulin resistance are frequently present. To this goal, 7 patients with essential hypertension (HP, age, mean +/- SE: 29.6 +/- 2.4 yr, 3 females and 4 males, BMI: 21.7 +/- 1.2 kg/m2), 7 obese (OB, 4 females and 3 males, 31.9 +/- 4.1 yr, 35.6 +/- 2.0 kg/m2) and 7 normal subjects (NS, 4 females and 3 males, 28.3 +/- 3.9 yr, 21.0 +/- 1.6 kg/m2) underwent the following tests: GHRH (1 microgram/kg i.v. at time 0) alone and preceded by oral glucose load (OGTT, 100 g po at -45 min). Basal insulin levels were similar in HP and OB (11.3 +/- 0.5 and 12.7 +/- 2.2 microU/ml, respectively); these, in turn, were higher (p < 0.005) than those in NS (6.8 +/- 0.8 microU/ml). Basal plasma glucose levels in HP were similar to those in OB and NS (80.3 +/- 3.6, 86.9 +/- 6.7 and 84.4 +/- 1.7 mg/dl, respectively). In HP and OB and NS basal GH (1.0 +/- 0.5, 1.0 +/- 0.6 and 0.3 +/- 0.1 micrograms/l, respectively) and IGF-I levels (132.6 +/- 14.8, 137.3 +/- 13.2 and 138.8 +/- 12.2 micrograms/l, respectively) were similar. In HP the GH response to GHRH (AUC: 1058.8 +/- 347.8 micrograms/l/min) was similar to that observed in NS (959.0 +/- 167.8 micrograms/l/min) and higher than that in OB (344.8 +/- 67.2 micrograms/l/min, p < 0.01). OGTT clearly blunted (p < 0.01) the GHRH-induced GH response in HP as well as in NS (401.8 +/- 104.4 and 521.6 +/- 76.6 (g/l/min, respectively) but not in OB (387.4 +/- 78.8 (g/l/min). The OGTT-induced insulin levels in HP did not differ from those of OB, both being higher (p < 0.05) than those recorded in NS. Glucose levels after OGTT were similar in the three groups. In conclusion, this study demonstrates that, like in normal subjects but differently from in obese patients the GH response to GHRH is normal in patients with essential hypertension and it is normally inhibited by oral glucose load even when these patients show high insulin levels. Thus, it is unlikely that the low somatotrope secretion and its refractoriness to inhibition by glucose load in obesity is due to hyperinsulinism.

Adult↗

PubMed1997

Effects of cholinergic blockade by pirenzepine on insulin and glucose response to oral and intravenous glucose and to arginine load in obesity.

Parasympathetic nervous system is known to affect insulin secretion in animal and man and there is evidence that it is involved in the outcome of spontaneous and stimulated insulin hypersecretion observed in animal obesity. In human obesity, there are contradictory data. We studied the effect of 150 mg orally administered pirenzepine (PNZ), a muscarinic receptor antagonist, on the insulin response to glucose (75 g p.o. or 0.33 g/kg i.b.w. i.v.) or arginine (0.5 g/kg infused in 30 min) in 18 obese subjects normotolerant to glucose. PNZ did not modify basal serum insulin and the hormone response to either intravenous glucose (AUC: 5221.6 +/- 1177:6 vs 5309.8 +/- 1534.8 mU/L.min) or arginine load (4257.9 +/- 832.7 vs 3952.8 +/- 549.3 mU/L.min). Calculated as AUC the insulin response to oral glucose load was unaffected by PNZ (6601.5 +/- 1218.6 vs 8614.3 +/- 1095.2 mU/L.min). Actually, the insulin rises at +30 min after oral glucose load was significantly blunted by PNZ (37.0 +/- 3.4 vs 81.6 +/- 16.9 mU/L; p < 0.03). However, after statistical evaluation by ANCOVA assuming basal insulin and +30 min glucose levels as covariates, this significant disappeared. Our present data do not agree with the hypothesis that the cholinergic system plays a role in the exaggerated insulin secretion of obesity. Nevertheless, these findings confirm that acetylcholine positively influences insulin secretion in humans, likely via indirect mechanisms.

Adult↗

PubMed1997

Comparison among the effects of arginine, a nitric oxide precursor, isosorbide dinitrate and molsidomine, two nitric oxide donors, on hormonal secretions and blood pressure in man.

Arginine has well-known stimulatory effects on GH, PRL and insulin secretion in man but the mechanisms underlying these effects are still unclear. More recently, it has been demonstrated that arginine is the precursor of nitric oxide (NO) which mediates its vasodilatatory effect. Thus, it has been hypothesized that NO could also mediate the hormonal effects of arginine. To clarify this point, in seven normal young volunteers (7 normal male subjects, age 26-35 yr) we compared the effects of arginine hydrochloride (ARG, 0.5 g/kg iv over 30 min) on GH, PRL, insulin and glucose levels as well as on blood pressure, with those of isosorbide dinitrate (ISDN, 5 mg po) and molsidomine (MOLS, 4 mg po), two NO donors which possess well-known vasodilatatory effects. ARG infusion elicited a clear-cut GH increase (peak vs baseline 17.6 +/- 4.7 vs 2.7 +/- 0.8 (g/L, p < 0.01), PRL (20.6 +/- 2.8 vs 6.9 +/- 0.5 (g/L, p < 0.01) and insulin levels (31.4 +/- 5.7 vs 4.5 +/- 2.1 (U/L, p < 0.01) while induced a biphasic variation of plasma glucose levels with early increase (p < 0.01), followed by late decrease below basal values (p < 0.01). On the other hand, blood pressure was decreased by ARG (nadir vs baseline; systolic: 103 +/- 6 vs 112 +/- 3, p < 0.02 and diastolic 61 +/- 4 vs 72 +/- 2 mmHg, p < 0.02, respectively). ISDN and MOLS did not modify basal GH, PRL and insulin as well as glucose levels while induced a clear reduction in blood pressure (ISDN: nadir vs baseline; systolic: 94 +/- 4 vs 112 +/- 2, p < 0.02; diastolic 69 +/- 3 vs 80 +/- 2, p < 0.02; MOLS: systolic: 94 +/- 3 vs 113 +/- 2 p < 0.02; diastolic 63 +/- 4 vs 72 +/- 2, p < 0.02). The lowering effect of both ISDN and MOLS on both systolic and diastolic blood pressure levels was higher than that induced by ARG. The effect of the latter was, in turn, significantly different from that of placebo on diastolic levels only. In conclusion, our present date are against the hypothesis that NO mediates the stimulatory effects of arginine on GH, PRL and insulin secretion. On the other hand, our findings agree with the hypothesis that ARG has NO-mediated vasodilatatory effect able to decrease blood pressure in man.

Adult↗

PubMed1997

Long-term treatment with cabergoline, a new long-lasting ergoline derivate, in idiopathic or tumorous hyperprolactinaemia and outcome of drug-induced pregnancy.

Cabergoline (CAB), a new long-acting ergoline derivative, was shown to be very effective in reducing PRL levels in normal volunteers and in hyperprolactinemic patients. We evaluated the hormonal changes after discontinuation of long-term therapy with CAB as well as the safety of drug exposure during pregnancy both for mothers and babies. We therefore studied 48 patients (47 females and one male) with pathological hyperprolactinaemia (mean +/- SE, 117.2 +/- 15.2: median 73.2 micrograms/l), treated for 1-82 months (mean +/- SE, 28.3 +/- 3; median 18). After long-term treatment, CAB was withdrawn in 11 patients and PRL levels were persistently normal for almost 15 days and significantly lower (p < 0.05) than basal at 30, 45, 60, 90, 120 days. Three patients had normal PRL levels still at 45 days after treatment discontinuation. Nine patients became pregnant after 1-37 months (mean 12.4) of therapy. In two patients the pregnancy was interrupted spontaneously in one case and voluntarily in the other. In all but one patients after delivery or three-month breast feeding, PRL levels trended towards reduction. In two cases (one with microadenoma and one with idiopathic hyperprolactinaemia) PRL remained in the normal levels for 1-3 years after delivery. In conclusion CAB is able to inhibit plasma PRL levels for long time (up to 120 days) after withdrawal in patients with pathological hyperprolactinaemia treated with long-term therapy.

Adenoma↗

PubMed1997

Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency.

OBJECTIVE: To evaluate the maximal secretory capacity of somatotrope cells in obesity and to compare it with that in hypopituitaric patients with GH deficiency. DESIGN: Stimulation with GHRH. (1 microgram/kg i.v.), combined with arginine (ARG, 0.5 g/kg i.v.), which strongly potentiates the GH response to the neurohormone, likely inhibiting hypothalamic somatostatin. The reproducibility of the GH response to GHRH + ARG was evaluated in a second session. SUBJECTS: Forty-five patients with simple obesity (OB 11 male and 34 female, age 40.5 +/- 1.8 y, BMI 38.8 +/- 1.1 kg/m2), 49 patients with hypopituitarism (GHD, 23 male and 26 female, 43.6 +/- 2.4 y, 24.7 +/- 0.7 kg/m2) and 44 normal young volunteers (NS, 25 male and 19 female, 33.8 +/- 1.0 y, 21.6 +/- 0.3 kg/m2) were studied. MEASUREMENTS: GH levels were assayed by IRMA method, basally at -60 and 0 min, and than every 15 min up to +120 min. Basal IGF-I levels were assayed by RIA method, after acid-ethanol extraction. RESULTS: IGF-I levels in OB were lower (P < 0.005) than those in NS but higher (P < 0.005) than those in GHD. Mean peak GH response to GHRH + ARG in OB was clearly lower than that in NS (P < 0.005) and higher (P < 0.005) than that in GHD. Sixty-percent OB and 100% GHD showed peak GH responses lower than the minimum normal limit in NS (16.5 micrograms/l) while 4% OB and only 53% GHD with GH responses lower than 3 micrograms/l, the limit under which GH replacement therapy of severe deficiency is allowed. Good intraindividual reproducibility of the GH response to GHRH + arginine test was present in all groups (OB: r = 0.78, P < 0.0001; GHD: r = 0.57, P < 0.003; NS: r = 0.74, P < 0.0001;. CONCLUSIONS: The maximal secretory capacity of somatotrope cells is clearly less than normal in the obese but still more than is seen in GHD subjects. However, in about 50% of obese patients, the pituitary GH releasable pool overlaps with that of hypopituitaric patients with GH deficiency. Thus, even when the maximal secretory capacity of somatotrope cells is evaluated by a potent and reproducible provocative tests such as GHRH + arginine, overweight has to be taken in a great account as the cause of severely impaired GH response in patients with suspected GH deficiency.

Adult↗

PubMed1997

Cholinergic enhancement by pyridostigmine increases the insulin response to glucose load in obese patients but not in normal subjects.

OBJECTIVE: To further investigate the role, if any, of acetylcholine and the parasympathetic nervous system in modulating beta-cell secretion in man. DESIGN: Oral glucose load (OGTT, 100 g p.o. at 0 min) alone and preceded by pyridostigmine (PD, 120 mg p.o., 60 min before OGTT), a cholinesterase inhibitor, were administered on two different occasions, in random order, two or three days apart. SUBJECTS: Ten women with central obesity (OB, body mass index (BMI): 34.2 +/- 2.1 kg/m2, waist to hip ratio (WHR): 0.83 +/- 0.01, aged 39.0 +/- 5.3y) and six normal women (NS, BMI: 22.7 +/- 1.9 kg/m2, WHR: 0.74 +/- 0.01, aged 37.1 +/- 4.8y) were studied. MEASUREMENTS: Serum insulin, plasma glucose and plasma noradrenaline (NA) were measured at -60, -15 and 0 min, and then every 15 min up to +120 min. Insulin concentrations were measured in duplicate by immunoradiometric assay, glucose by glucose oxidase colorimetric method and NA was assayed after extraction with alumina using high performance liquid chromatography with electrochemical detection. Pulse rate (PR), systolic (SBP) and diastolic blood pressure (DBP) were also measured every 15 min during the tests by an automated cuff device. RESULTS: OGTT raised glucose concentrations in OB and NS (incremental area: 420 +/- 44 vs 288 +/- 70 mmol/l. 2 h, respectively) without significant differences between groups (F = 0.6, P = ns). On the other hand, OB showed an insulin response to OGTT higher than NS (10,120 +/- 1074 vs 6692 +/- 1962 microU ml-1 2 h, respectively P < 0.01). After OGTT alone NA concentrations increased to the same extent in NS (peak vs basal: 1.40 +/- 0.16 vs 1.07 +/- 0.10 nmol/l, P < 0.05) and in OB (peak vs basal: 1.50 +/- 0.14 vs 1.04 +/- 0.18 nmol/l P < 0.05). Both in NS and in OB, PD administration failed to modify basal glucose and insulin (P = ns for both) as well as basal NA concentrations. In NS, the combined administration of PD and OGTT did not modify glucose and insulin responses compared to OGTT alone 335 +/- 65.4 mmol/l. 2h and 6348 +/- 1348 microU ml-1 2h, respectively) while in OB, PD significantly increased the insulin response to OGTT (14640 +/- 3030 microU ml-1 2h, P < 0.03), while the glucose response was not significantly different from OGTT alone (478 +/- 45 mmol/l. 2h). PD administration did not modify the NA response to OGTT, in NS or OB (P = ns). In both groups, pyridostigmine administration did not affect systolic or diastolic blood pressures, but decreased pulse rate to the same extent in NS (74 +/- 2 vs 66 +/- 2 beats/min, P < 0.05) and in OB (72 +/- 1 vs 67 +/- 2 beats/min, P < 0.05). CONCLUSIONS: Our present data indicate that in man, as in animals, acetylcholine has a stimulatory influence on insulin secretion.

Abdomen↗

PubMed1997

In obesity, glucose load loses its early inhibitory, but maintains its late stimulatory, effect on somatotrope secretion.

Glucose load has a biphasic effect on GH secretion. In fact, in normal subjects, glucose load has a prompt inhibitory and a late stimulatory effect on both spontaneous and GHRH-induced GH levels. The mechanism underlying the inhibitory effect is probably mediated by the increase in hypothalamic somatostatin, whereas that underlying the stimulatory effect is unclear. On the other hand, in obesity, a reduced somatotrope responsiveness to all GH secretagogues is well known, whereas recently, we found that glucose load, but not pirenzepine and somatostatin, fails to inhibit the GHRH-induced GH rise. Thus, the inhibitory effect of hyperglycemia on GH secretion is selectively lacking in obesity. The aim of the present study was to verify whether in obesity the late stimulatory effect of glucose on GH secretion is preserved. We studied 15 female obese patients (OB; age, 33.9 +/- 2.6 yr; body mass index, 36.4 +/- 1.5 kg/m2; waist/hip ratio, 0.9 +/- 0.1) and 12 normal female subjects (NS; 26.5 +/- 1.0 yr; 21.4 +/- 0.3 kg/m2) as controls. Two studies were performed. In study A (six OB and six NS) we evaluated the somatotrope response to GHRH (1 microgram/kg, i.v., at 0 min) alone or preceded by oral glucose (OGTT; 100 g, orally, at -45 min). In study B (nine OB and six NS) we studied the somatotrope response to OGTT (100 g, orally, at 0 min), saline plus GHRH (1 microgram/kg, iv, at 150 min), and OGTT plus GHRH. In study A, the GHRH-induced GH rise in NS was higher (P < 0.01) than that in OB. OGTT blunted the GHRH-induced GH rise in NS (0-90 min area under the curve, 318.9 +/- 39.1 vs. 696.3 +/- 110.8 micrograms/min-L; P < 0.05), but failed to modify it in OB (289.1 +/- 51.7 vs. 283.9 +/- 44.0 micrograms/min-L). In study B, the GHRH-induced GH rise in NS was higher (P < 0.01) than that in OB. OGTT induced a late GH increase in both NS (150-240 min area under the curve, 249.6 +/- 45.2 micrograms/min-L) and OB (103.2 +/- 31.4 micrograms/min-L). Moreover, OGTT enhanced the GHRH-induced GH rise in NS as well as in OB [1433.0 +/- 202.0 vs. 967.9 +/- 116.3 micrograms/min-L (P < 0.03) and 763.8 +/- 131.0 vs. 278.1 +/- 52.3 micrograms/min-L (P < 0.01), respectively]. The GH responses to OGTT alone and combined with GHRH in OB were lower (P < 0.03) than those in NS. Our data show that in human obesity, the oral glucose load loses its precocious inhibitory effect on the GHRH-induced GH rise but maintains its late stimulatory effect on somatotrope secretion. These findings suggest that the inhibitory and stimulatory effects of glucose load on GH secretion are unlikely to be due to biphasic modulation of hypothalamic somatostatin release, which seems selectively refractory to stimulation by hyperglycemia in obesity.

Adult↗

PubMed1997

[Growth hormone and lipids].

Growth hormone (GH), Insulin Growth Factor-I (IGF-I) and lipids are linked by important reciprocal influences. Their knowledge allowed relevant pathophysiological and clinical acquisitions more and more interesting in scientific research and in medical practice. In this survey the influence of (GH) on lipid metabolism, particularly on free fatty acids (FFA) and lypoprotein metabolism has been analysed. Attention has been given to the disorders of the lipid-metabolism in GH hypo- and hyper-secretory states. On the other hand the role of lipids in the control of GH secretion has been extensively considered with particular attention to the role of exaggerated FFA levels in the pathogenesis of GH insufficiency in obesity.

English Abstract↗

PubMed1996

Galanin positively modulates prolactin secretion in normal women.

It is widely accepted that, in man, galanin, a neuropeptide, has a clear GH-releasing effect while its stimulatory influence on PRL secretion is matter of debate. To clarify this point, in 6 normal young women (23-35 yr) in their early follicular phase, we studied the effect of galanin (pGAL, 80 pmol/kg. min infused i.v. over 60 min) on both basal and arginine (ARG, 0.5 g/kg i.v. in 30 min), TRH (400 micrograms i.v. as a bolus at 0 min) or metoclopramide (MCP, 10 mg i.v. as a bolus at 0 min)-stimulated PRL secretion. GAL infusion failed to significantly increase basal PRL levels (peak vs baseline: 12.2 +/- 3.6 vs 8.7 +/- 1.2 micrograms/L) but counteracted the spontaneous PRL decrease observed during saline infusion (AUC: 1216.6 +/- 282.1 vs 672.0 +/- 94.5 micrograms.min/L; p < 0.05). GAL infusion clearly enhanced the PRL response to TRH (AUC: 5806.3 +/- 743.0 vs 3952.1 +/- 423.9 micrograms.min/L, p < 0.05) and ARG (AUC: 3676.8 +/- 382.6 vs 2638.9 +/- 287.0 micrograms.min/L, p < 0.05), respectively. On the other hand, GAL failed to modify the MCP-induced PRL response (AUC: 15409.5 +/- 2085.3 vs 14,787.9 +/- 2045.5 micrograms.min/L). The PRL response to MCP was higher than that to TRH (p < 0.01) which, in turn, was higher than that to ARG (p < 0.01). During GAL infusion, the PRL response to TRH or ARG remained lower (p < 0.01) than that after MCP administration. Thus, in conclusion, present data demonstrate that in normal women galanin enhances the PRL response to ARG and TRH but fails to modify that induced by dopamine receptor blockade with metoclopramide. Based on evidence that the inhibition of central dopaminergic activity inhibits the lactotrope responsiveness to dopaminergic antagonists or TRH, it is unlikely that galanin influences PRL secretion via inhibition of dopaminergic tone.

Adult↗

PubMed1996

Effect of bromocriptine on insulin, growth hormone and prolactin responses to arginine in obesity.

Dopaminergic system seems to influence the regulation of insulin secretion, although in man conflicting data are reported. Furthermore, bromocriptine (BRC), a dopaminergic agonist, has been recently found to inhibit the seasonally occurring hyperinsulinemia and the increase in body weight in the hamster. On this basis, we investigated the effect of BRC on spontaneous and stimulated insulin secretion in human obesity. Six obese (BMI: 33.2 +/- 1.6 Kg/m2) underwent the administration of: 1) arginine (ARG, 0.5 g/Kg iv in 30 min), 2) BRC (2.5 mg po), 3) ARG+BRC. In each test plasma glucose and serum insulin, growth hormone (GH) and prolactin levels were determined. BRC did not significantly reduce spontaneous and ARG-induced insulin release. Baseline and stimulated glucose levels were also unchanged. BRC determined an increase in GH levels (3.7 +/- 1.3 vs 0.5 +/- 0.3 microgram/l, p < 0.05), but failed to modify the somatotrope responsiveness to ARG. On the other hand, both spontaneous and stimulated PRL secretion were reduced by BRC (2.5 +/- 0.4 vs 6.7 +/- 1.1 micrograms/l, p < 0.05 and 0.8 +/- 1.9 vs 11.0 +/- 2.1 micrograms/l, p < 0.05, respectively). Our results show that in obese patients the acute activation of dopaminergic receptors by bromocriptine fails to modify both basal and ARG-induced insulin release, while inhibits spontaneous and stimulated PRL secretion. Our data also show that the low GH response to arginine in obesity is not improved by the coadministration of bromocriptine, in agreement with the hypothesis that both substances act by the same mechanism, i.e. inhibition of endogenous somatostatin release.

Adolescent↗