RESUMEN
BACKGROUND: The physiological inhibitory control of glucagon-like Peptide 1 (GLP-1) on gastric emptying and the contribution of this peptide in the regulation of food intake as a satiety factor suggest that impaired secretion and/or activity of GLP-1 may be involved in the pathogenesis of obesity. We investigated food-mediated GLP-1 secretion as well as plasma activity of dipeptidyl-peptidase IV (DPP-IV), the enzyme responsible for rapid inactivation of the circulating peptide, in morbidly obese patients, before and after weight loss resulting from biliopancreatic diversion. METHODS: Twenty-two morbidly obese non-diabetic patients (BMI = 47.5 +/- 1.8) and 9 age-matched healthy volunteers were studied. A mixed meal (700 kcal) was administered to all subjects and blood samples were collected at 0, 15, 30, 60, 120 min for the determination of circulating glucose, insulin, GLP-1 (7 - 36 amide) concentrations and plasma DPP-IV activity. The patients repeated the test meal after 50 % overweight reduction resulting from surgical treatment (BMI = 33.8 +/- 1.1). RESULTS: While nutrient ingestion significantly increased plasma GLP-1 levels in the control group (30', 60': p < 0.01), the test-meal failed to modify basal peptide values in the obese patients, and an overall reduction in circulating GLP-1 occurred during the observation period (p < 0.001). Plasma DPP-IV activity in the same patients resulted as being significantly higher than controls, both at fasting and in response to the meal (p < 0.05). With respect to preoperative values, an overall increase in circulating GLP-1 levels occurred in all patients following biliopancreatic diversion (p < 0.001). Plasma DPP-IV activity, on the other hand, continued to be abnormally increased, even after considerable weight loss (p < 0.05 vs. controls). CONCLUSIONS: First: In morbid obesity, the accelerated inactivation of circulating GLP-1 could at least partially account for plasma peptide levels lower than normal, the defective availability of such a satiety factor possibly contributing to eating behaviour abnormalities; Second: plasma DPP-IV hyperactivity in the obese did not seem to be affected by the overweight degree, the increase in postoperative GLP-1 levels mainly resulting from hyperstimulation of GLP-1 secretory cells due to surgical manipulation of gastrointestinal tract. If the abnormally accelerated degradation of GLP-1 in obesity is confirmed, selective DPP-IV inhibitors could actually represent an ideal approach to obesity management.
Asunto(s)
Desviación Biliopancreática , Dipeptidil Peptidasa 4/sangre , Glucagón/metabolismo , Obesidad Mórbida/metabolismo , Obesidad Mórbida/cirugía , Fragmentos de Péptidos/metabolismo , Precursores de Proteínas/metabolismo , Adulto , Ingestión de Alimentos , Femenino , Péptido 1 Similar al Glucagón , Humanos , Masculino , Obesidad Mórbida/sangre , Obesidad Mórbida/fisiopatología , Periodo Posoperatorio , Pérdida de PesoRESUMEN
UNLABELLED: To investigate a possible role of an enteroinsular axis involvement in the pathogenesis of type 2 diabetes, plasma glucagon-like peptide 1 (GLP-1) 7-36 amide response to nutrient ingestion was evaluated in type 2 diabetics affected by different degrees of beta-cell dysfunction. METHODS: 14 patients on oral hypoglycaemic treatment (group A: HbA1C = 8.1 +/- 1.8 %) and 11 age-matched diabetic patients on diet only (group B: HbA1C = 6.4 +/- 0.9) participated in the study. 10 healthy volunteers were studied as controls. In the postabsorptive state, a mixed meal (700 kCal) was administered to all subjects, and blood samples were regularly collected up to 180' for plasma glucose, insulin, glucagon, and GLP-1 determination. RESULTS: In the control group, the test meal induced a significant increase in plasma GLP-1 at 30' and 60' (p < 0.01); the peptide concentrations then returning toward basal levels. beta-cell function estimation by HOMA score confirmed a more advanced involvement in group A than in group B (p < 0.01). In contrast, the insulin resistance degree showed a similar result in the two groups (HOMA-R). In group A, first-phase postprandial insulin secretion (0 - 60') resulted, as expected, in being significantly reduced compared to healthy subjects (p < 0.001). In the same patients the mean fasting GLP-1 value was similar to controls, but the meal failed to increase plasma peptide levels, which even tended to decrease during the test (p < 0.01). In group B, food-mediated early insulin secretion was higher than in group A (p < 0.001), although significantly reduced when compared to controls (p < 0.01). Like group A, no GLP-1 response to food ingestion occurred in group B patients in spite of maintained basal peptide secretion. Whereas the test-meal did not significantly modify plasma glucagon levels in the control group, glucagon concentrations increased at 30' and 60' in both diabetic groups (p < 0.01). CONCLUSIONS: 1) The functional integrity of GLP-1 cells results as being seriously impaired even in the condition of mild diabetes; 2) the early peptide failure could contribute to the development of beta-cell deterioration which characterizes overt type 2 diabetes.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Glucagón/farmacología , Insulina/sangre , Fragmentos de Péptidos/farmacología , Precursores de Proteínas/farmacología , Anciano , Glucemia/metabolismo , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Progresión de la Enfermedad , Ingestión de Alimentos/fisiología , Femenino , Glucagón/sangre , Péptido 1 Similar al Glucagón , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Precursores de Proteínas/sangreRESUMEN
The urinary excretion of insulinotropic glucagon-like peptide 1 (GLP-1) was investigated as an indicator of renal tubular integrity in 10 healthy subjects and in 3 groups of type 2 diabetic patients with different degrees of urinary albumin excretion rate. No significant difference emerged between the groups with respect to age of the patients, known duration of diabetes, metabolic control, BMI, or residual beta-cell pancreatic function. Endogenous creatinine clearance was significantly reduced under conditions of overt diabetic nephropathy, compared with normo and microalbuminuric patients (p < 0.01). Urinary excretion of GLP-1 was significantly higher in normoalbuminuric patients compared to controls (490.4 +/- 211.5 vs. 275.5 +/- 132.1 pg/min; p < 0.05), with further increase under incipient diabetic nephropathy conditions (648.6 +/- 305 pg/min; p < 0.01). No significant difference resulted, in contrast, between macroproteinuric patients and non-diabetic subjects. Taking all patients examined into account, a significant positive relationship emerged between urinary GLP-1 and creatinine clearance (p = 0.004). In conclusion, an early tubular impairment in type 2 diabetes would occur before the onset of glomerular permeability alterations. The tubular dysfunction seems to evolve with the development of persistent microalbuminuria. Finally, the advanced tubular involvement, in terms of urinary GLP1 excretion, under overt diabetic nephropathy conditions would be masked by severe concomitant glomerular damage with the coexistence of both alterations resulting in a peptide excretion similar to control subjects.
Asunto(s)
Diabetes Mellitus Tipo 2/orina , Fragmentos de Péptidos/orina , Anciano , Albuminuria/orina , Índice de Masa Corporal , Péptido C/sangre , Creatinina/sangre , Creatinina/orina , Nefropatías Diabéticas/orina , Femenino , Glucagón , Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Hemoglobina Glucada/análisis , Humanos , Masculino , Tasa de Depuración Metabólica , Persona de Mediana EdadRESUMEN
Exogenous glucagon-like peptide 1(GLP-1) bioactivity is preserved in type 2 diabetic patients, resulting the peptide administration in a near-normalization of plasma glucose mainly through its insulinotropic effect. GLP-1 also reduces meal-related insulin requirement in type 1 diabetic patients, suggesting an impairment of the entero-insular axis in both diabetic conditions. To investigate this metabolic dysfunction, we evaluated endogenous GLP-1 concentrations, both at fasting and in response to nutrient ingestion, in 16 type 1 diabetic patients (age = 40.5 +/- 14yr, HbA1C = 7.8 +/- 1.5%), 14 type 2 diabetics (age = 56.5 +/- 13yr, HbA1C = 8.1 +/- 1.8%), and 10 matched controls. In postabsorptive state, a mixed breakfast (230 KCal) was administered to all subjects and blood samples were collected for plasma glucose, insulin, C-peptide and GLP-1 determination during the following 3 hours. In normal subjects, the test meal induced a significant increase of GLP-1 (30', 60': p < 0.01), returning the peptide values towards basal concentrations. In type 2 diabetic patients, fasting plasma GLP-1 was similar to controls (102.1 +/- 1.9 vs. 97.3 +/- 4.01 pg/ml), but nutrient ingestion failed to increase plasma peptide levels, which even decreased during the test (p < 0.01). Similarly, no increase in postprandial GLP-1 occurred in type 1 diabetics, in spite of maintained basal peptide secretion (106.5 +/- 1.5 pg/ml). With respect to controls, the test meal induced in both diabetic groups a significant increase in plasma glucagon levels at 60' (p < 0.01). In conclusion, either in condition of insulin resistance or insulin deficiency chronic hyperglycemia, which is a common feature of both metabolic disorders, could induce a progressive desensitization of intestinal L-cells with consequent peptide failure response to specific stimulation.
Asunto(s)
Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ingestión de Alimentos/fisiología , Hormonas Gastrointestinales/metabolismo , Glucagón/metabolismo , Fragmentos de Péptidos/metabolismo , Adulto , Glucemia/metabolismo , Femenino , Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , RadioinmunoensayoAsunto(s)
Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 2/complicaciones , Glucemia/análisis , Automonitorización de la Glucosa Sanguínea , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/epidemiología , Ayuno/sangre , Femenino , Hemoglobina Glucada/análisis , Humanos , Insulina/sangre , Masculino , Factores de Riesgo , Factores SexualesRESUMEN
The existence of a linkage between retinal and renal microvascular complications in type 2 diabetes has been so far little investigated. For this purpose we evaluated the presence and degree of renal dysfunction in the most serious clinical conditions of diabetic retinopathy. On the basis of the alterations evidenced by fluorescein angiography 73 type 2 diabetic patients were recruited and divided into the following groups: 19 patients were affected by "clinically significant" Macular Edema (ME), 25 subjects had Preproliferative Retinopathy (PrePR) and 29 patients showed Proliferative Retinopathy (PR). Mean values (M +/- SD) of glycosylated hemoglobin, plasma basal C-peptide, lipid profile, blood pressure, glomerular filtration rate, body mass index, age and known duration of diabetes were similar between the groups. Urinary albumin excretion rate (UAE) was determined for each patient on three consecutive overnight collections (pg/min). Even though the distribution of normo (UAE < 20 micrograms/min), micro (UAE:20-200) and macroalbuminuric (UAE > 200) patients did not significantly differ between the groups, mean values of UAE increased significantly in PrePR (371.1 +/- 532.2) and PR (300.7 +/- 717.3) with respect to ME (35.4 +/- 73.1; p < 0.05). The evaluation of all patients recruited for the study, independently of the kind of retinal alteration, showed that 56.8% of them had no sign of even incipient renal dysfunction, in spite of the advanced retinal damage. When considering those patients affected by both retinal and renal complications (43.2%) the prevalence of renal involvement resulted different in the three conditions investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/fisiopatología , Retinopatía Diabética/fisiopatología , Albuminuria/etiología , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/etiología , Retinopatía Diabética/etiología , HumanosAsunto(s)
Péptido C/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Riñón/metabolismo , Adolescente , Adulto , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/fisiopatología , Femenino , Tasa de Filtración Glomerular , Hemoglobina Glucada/análisis , Humanos , Insulina/uso terapéutico , Riñón/fisiología , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Valores de Referencia , Circulación RenalRESUMEN
The effect of somatostatin (SRIH) on the release of oxytocin (OT) in response to hypoglycemia during insulin tolerance test (ITT) was studied in seven normal men. Subjects were injected intravenously with 0.15 U/kg insulin alone (control test) or together with SRIH (4.1 micrograms/min x 90 min), naloxone (10 mg in an IV bolus), or the combination of the two substances. Plasma OT concentrations rose significantly during ITT; the OT response was significantly reduced by the treatment with SRIH and increased in the presence of naloxone. When both SRIH and naloxone were given, the OT response to hypoglycemia did not differ from that observed in the control test. These findings provide evidence that the effect of hypoglycemia on plasma OT levels is sensitive to the inhibition by SRIH and by naloxone-sensitive endogenous opioids. Because naloxone reversed the inhibiting effects of SRIH, an involvement of opioid peptides in SRIH action might be supposed. Alternatively, SRIH and naloxone-sensitive opioids might produce their inhibiting effects on OT rise in response to hypoglycemia through independent pathways.
Asunto(s)
Hipoglucemia/sangre , Insulina , Naloxona/farmacología , Oxitocina/metabolismo , Somatostatina/farmacología , Adulto , Interacciones Farmacológicas , Humanos , Cinética , Masculino , Oxitocina/sangreRESUMEN
The effect of an iv infusion of somatostatin (SRIH) (4.1 micrograms/min x 90 min) on the basal secretion of arginine-vasopressin (AVP) and on the AVP response to insulin (0.15 IU/Kg) - induced hypoglycemia was studied in 6 normal men. Basal AVP secretion was not modified by SRIH administration. The blood glucose decrements induced by insulin were similar in the control insulin-tolerance test (ITT) and in the ITT + SRIH test, whereas the AVP response to hypoglycemia was significantly lower in the presence of SRIH. The mean peak AVP increase was three times higher than the basal value in the control ITT, but only two times during SRIH administration. Infusion of higher doses of SRIH (7 micrograms/min x 90 min) produced similar results. These data suggest the involvement of a somatostatinergic mechanism in regulation of AVP response to hypoglycemia.
Asunto(s)
Arginina Vasopresina/sangre , Hipoglucemia/sangre , Somatostatina/farmacología , Hormona Adrenocorticotrópica/sangre , Adulto , Glucemia/análisis , Glucagón/sangre , Hormona del Crecimiento/sangre , Humanos , Hipoglucemia/inducido químicamente , Infusiones Intravenosas , Insulina , MasculinoRESUMEN
The thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) responses to thyrotropin releasing hormone (TRH), the Wechsler Adult Intelligence Scale (WAIS) for cognitive impairment, and computed tomographic scans were evaluated in 15 nondepressed alcoholic men after 4 weeks of abstinence and in 10 normal controls. Both cognitive impairment and cerebral atrophy were found in 13 of the alcoholics. Eight alcoholics (seven with cerebral atrophy) had blunted TSH and PRL responses to TRH and a TRH-induced paradoxical increase of GH. This study demonstrates that besides affecting the TSH response to TRH, alcoholism often induces alterations of the PRL and GH secretory patterns in response to TRH. The severe brain damage caused by long-term alcoholism might be involved in the pathogenesis of these neuroendocrine alterations.
Asunto(s)
Alcoholismo/rehabilitación , Encéfalo/patología , Hormona del Crecimiento/sangre , Prolactina/sangre , Templanza , Hormona Liberadora de Tirotropina , Tirotropina/sangre , Adulto , Alcoholismo/sangre , Atrofia , Humanos , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/sangre , Tomografía Computarizada por Rayos XRESUMEN
In order to evaluate the possible influence of GABAergic neurotransmission on the arginine vasopressin (AVP) response to osmotic and pressure volumetric stimuli, the GABAergic drug sodium valproate was administered by mouth (200 or 400 mg 16 h, 8 h and just before tests) to eight normal men before osmotic (i.v. infusion of 0.51 , NaCl for 2 h) and orthostatic (standing upright and maintaining an orthostatic position for 20 min) tests. In both experimental conditions, the AVP rise was significantly lower in the presence than in absence of sodium valproate. The maximum AVP responses in the control orthostatic and osmotic tests were respectively 2.3 and 2.5 times higher than basal levels. When 600 mg sodium valproate was given, the maximum AVP rise in response to hypovolaemic and osmotic stimuli were respectively 1.75 and 2.1 times higher than basal value. Similar results were obtained giving 1.2 g sodium valproate. These results suggest that in man a GABAergic pathway is involved in the AVP responses to hypovolaemic and hyperosmotic stimuli.
Asunto(s)
Arginina Vasopresina/sangre , Postura/fisiología , Receptores de GABA-A/fisiología , Solución Salina Hipertónica , Ácido Valproico/farmacología , Adulto , Arginina Vasopresina/metabolismo , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Hematócrito , Humanos , Masculino , Concentración Osmolar , Receptores de GABA-A/efectos de los fármacosRESUMEN
High efficiency hemofiltration (HF) was carried out for 9 months in 6 patients on hemodialysis (HD). Comparative studies on carbohydrate metabolism and 500- to 1,500-dalton serum solute concentrations were performed during HD and HF. After 5 months of HF, intravenous glucose tolerance tests showed an improved peripheral glucose utilization, with unchanged insulin secretion. Larger solute concentrations, measured by gel chromatography, simultaneously dropped in serum suggesting that HF removes some toxic substances that inhibit peripheral insulin action. After 9 months of HF, an unexpected increase in the larger solute concentration coincided with an impaired glucose tolerance, stressing the probable toxic rule of such solutes. Changes in other glucoregulatory hormone secretions were not unequivocal. On account of the later increase in 500- to 1,500-dalton solute concentrations, HF failed to prevent larger toxic molecules accumulating in uremic sera.
Asunto(s)
Anuria/sangre , Glucemia/análisis , Hemofiltración , Anuria/terapia , Glucagón/sangre , Hormona del Crecimiento/sangre , Humanos , Insulina/sangre , Tasa de Depuración Metabólica , Persona de Mediana Edad , Peso Molecular , Prolactina/sangre , Diálisis Renal , Urea/sangreRESUMEN
The plasma oxytocin response to insulin-induced hypoglycemia was evaluated in 20 normal male subjects in the basal state (insulin tolerance test (ITT) alone) and after pretreatment with the muscarinic antagonist pirenzepine (40 mg IV 10 min before the ITT in six subjects), the nicotinic antagonist trimethaphan (0.3 mg/min IV for 30 min before the ITT in six subjects), and the dopaminergic receptor agonist bromocriptine (2.5 mg PO 1 hr before the ITT in eight subjects). The drugs did not modify arterial blood pressure nor produce side effects capable of altering oxytocin secretion. Neither pirenzepine nor trimethaphan administration changed the oxytocin response to hypoglycemia, whereas bromocriptine significantly reduced the oxytocin increase during the ITT. These data suggest the involvement of dopaminergic, but not of cholinergic, muscarinic or nicotinic, receptors in the oxytocin response to hypoglycemia.
Asunto(s)
Hipoglucemia/sangre , Oxitocina/sangre , Receptores Colinérgicos/fisiología , Receptores Dopaminérgicos/fisiología , Adulto , Glucemia/metabolismo , Bromocriptina , Humanos , Insulina , Insulina Regular Porcina , Masculino , Pirenzepina , Neurohipófisis/fisiología , Receptores Muscarínicos/fisiología , Receptores Nicotínicos/fisiología , TrimetafanRESUMEN
The metabolic effects of calcium channels blockers have already been studied both in normal and diabetic humans and results were quite controversial, depending on the drug used, the dose administered, and the type of patient. Little information exists on the use of Ca2+ antagonists in obese people, even if these persons are a population risk group for developing diseases in which these drugs may be requested for treatment. Thus, we evaluated, in obese humans, the metabolic effects of two Ca2+ antagonist drugs recently made commercially available to treat diseases such as hypertension and ischemic heart disease: nicardipine and diltiazem. Sixteen obese subjects were submitted to an intravenous glucose tolerance test (0.33 g/kg) (IVGTT) and an arginine test tolerance (30 g in 30 minutes) (ATT) before and after a week of oral treatment with nicardipine (60 mg/day) or diltiazem (360 mg/day). Plasma values of glucose, insulin, and C-peptide during IVGTT, and of glucose, insulin and glucagon during ATT did not show any modification during treatment with either drug. Thus the Ca2+ antagonists, nicardipine and diltiazem, at therapeutic doses in obese subjects do not significantly affect glucose tolerance or insulin and glucagon release.
Asunto(s)
Arginina/farmacología , Diltiazem/farmacología , Glucosa/farmacología , Insulina/sangre , Nicardipino/farmacología , Obesidad/sangre , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , MasculinoRESUMEN
To evaluate whether the inhibitory control exerted by endogenous dopamine on thyroid-stimulating hormone (TSH) secretion is altered in patients with major depressive disorder, 11 depressed patients and 9 normal controls were tested with the dopaminergic receptor antagonist domperidone (10 or 20 mg i.v.). The administration of domperidone induced a significant increase in circulating TSH levels in the normal controls, but not in the depressed patients. These data excluded the possibility that the dopaminergic inhibition of TSH secretion is enhanced in depression. To establish whether domperidone failure was due to a reduced dopaminergic tone, domperidone was administered before stimulation of TSH secretion with thyrotropin-releasing hormone (TRH) (200 micrograms i.v.). The TSH response to TRH was significantly lower in the depressed than in the control subjects, regardless of domperidone priming. However, in both groups domperidone enhanced the TRH-induced TSH release by 50%. These data suggest that the dopaminergic control of TSH secretion is not altered in patients with endogenous depression and that a reduced capacity of the pituitary to secrete TSH might be responsible for the reduced TSH responsiveness to TRH and domperidone.
Asunto(s)
Encéfalo/fisiopatología , Trastorno Depresivo/fisiopatología , Domperidona , Receptores Dopaminérgicos/fisiología , Tirotropina/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hormona Liberadora de TirotropinaRESUMEN
In order to test the possible effects of lysine vasopressin (LVP) on basal and TRH stimulated TSH and PRL release, an iv bolus of LVP (0.06 IU/kg bw) was injected alone or just before TRH (20 or 400 micrograms iv) in 18 normal male subjects. The administration of LVP modified neither the basal secretion of TSH and PRL nor the TSH and PRL release induced by 20 or 400 micrograms TRH. These data suggest that in humans, vasopressin is not involved in the control of TSH and PRL release at the anterior pituitary level.
Asunto(s)
Lipresina/farmacología , Prolactina/sangre , Hormona Liberadora de Tirotropina/farmacología , Tirotropina/sangre , Adulto , Análisis de Varianza , Humanos , Masculino , Valores de ReferenciaRESUMEN
The circulating levels of aldosterone (A), cortisol (F), prolactin, ACTH and potassium and the PRA were studied in 8 (6 males and 2 females) healthy normotensive subjects after 5-hydroxy-tryptophan (5OHT), or pizotifen (Piz) or placebo oral administration. In the same subjects 5OHT was administered twice: after placebo and after dexamethasone pretreatment. The results showed a significant increase of A, ACTH and F after 5OHT plus placebo administration without any change of PRA, potassium or prolactin levels; dexamethasone pretreatment suppressed ACTH and F but was uneffective on the response of A to 5OHT. Only A levels showed a significant decrease after Piz administration, the other studied parameters were unaffected by the blockade of the 5HT2 receptors by Piz. The administration of placebo induced a slight but not significant decrease of the studied parameters. Our results suggest the existence of a physiologic serotonergic control of A secretion, a pituitary factor could be one of the putative links between the central serotonergic activation and the adrenal secretory response.
Asunto(s)
5-Hidroxitriptófano/farmacología , Aldosterona/metabolismo , Pizotilina/farmacología , Serotonina/fisiología , Tiofenos/farmacología , Hormona Adrenocorticotrópica/sangre , Aldosterona/sangre , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Potasio/sangre , Prolactina/sangre , Renina/sangreRESUMEN
The present study was carried out in order to determine whether insulin-induced hypoglycemia exerts its stimulatory effect on plasma concentrations of arginine vasopressin (AVP) by interacting with a serotonergic, a GABA-ergic or an opioid pathway. For this purpose, the effect of the serotonergic antagonist metergoline (10 mg/day for 4 days po), the GABA-ergic agonist sodium valproate (600 mg in three divided doses po) and the opioid-receptor blocker naloxone (10 mg in a iv bolus) on the AVP response during an insulin (0.15 IU/kg bw) tolerance test (ITT) was evaluated in three groups of 6 normal men each. In all men, control ITTs were performed without drug treatments. Basal and ITT-stimulated AVP secretion was not modified by drug administration, suggesting that serotonergic, GABAergic and naloxone-sensitive opioid receptors are not involved in the regulation of AVP secretion in response to insulin-induced hypoglycemia.
Asunto(s)
Arginina Vasopresina/sangre , Ergolinas/farmacología , Hipoglucemia/sangre , Insulina/farmacología , Metergolina/farmacología , Naloxona/farmacología , Ácido Valproico/farmacología , Hormona Adrenocorticotrópica/sangre , Adulto , Hormona del Crecimiento/sangre , Humanos , Hipoglucemia/inducido químicamente , Masculino , Ácido gamma-Aminobutírico/fisiologíaRESUMEN
We have evaluated three regimens for the rapid control (10 days' therapy) of thyrotoxicosis in hyperthyroid Graves' disease: methimazole (MMI, 40 mg/day), MMI and sodium ipodate (MMI + Na Ipodate, 1 g/day and MMI and saturated solution of potassium iodide (MMI + SSKI, 6 drops twice daily). When serum T4 and T3 concentrations were analysed as the percent change from pre-treatment values, the following results were observed. Serum T4 concentration decreased in the three treatment groups and the decrease was similar in the MMI and MMI + SSKI groups but significantly lower than in the MMI + Na ipodate group. The serum T3 concentration decreased to the normal range in all seven MMI + Na Ipodate treated patients by the fourth day of treatment and the per cent decrease in serum T3 from pre-treatment values was significantly greater than in the MMI and MMI + SSKI treated patients. The decrease in serum T3 was similar in the latter two groups. Heart rate decreased in all three groups, but the decrease was significantly more in the MMI + Na Ipodate-treated patients. The present findings suggest that the rapid control of hyperthyroid Graves' disease is similar in patients treated with MMI and MMI + SSKI and that the combination of MMI + Na Ipodate is more efficacious since the decrease in serum T3 concentrations and heart rate was significantly greater in the MMI + Na ipodate-treated patients.