RESUMEN
Rates of diabetes and its complications have reached epidemic proportions among North American Aboriginal peoples. This appears largely due to changes in diet and activity levels associated with a shift away from traditional lifestyles. Since exercise has been shown to be effective in preventing non-insulin-dependent diabetes mellitus (NIDDM), Aboriginal communities may be able to reduce their rates of the disease by incorporating exercise programs into their public health programs. We describe a pilot project in Saskatoon, Saskatchewan, whose ultimate purpose is to evaluate the effect of exercise in preventing gestational diabetes. If successful, this would reduce the risk of developing NIDDM for both women and their offspring.
Asunto(s)
Diabetes Mellitus Tipo 2/prevención & control , Diabetes Gestacional/prevención & control , Ejercicio Físico , Embarazo en Diabéticas/prevención & control , Adolescente , Adulto , Indio Americano o Nativo de Alaska/estadística & datos numéricos , Regiones Árticas/epidemiología , Canadá/epidemiología , Niño , Preescolar , Diabetes Mellitus Tipo 2/etnología , Diabetes Gestacional/etnología , Femenino , Humanos , Estilo de Vida , Masculino , Proyectos Piloto , Embarazo , Resultado del Embarazo , Embarazo en Diabéticas/etnología , Prevención Primaria/métodos , PronósticoRESUMEN
Validation of evaluation methods is necessary in order to appropriately monitor Patellofemoral Pain Syndrome (PFPS) patients and to determine the effectiveness of treatment and prevention programs. The goal of this study was to investigate the psychometric properties of five evaluation methods: a functional index questionnaire (FIQ), visual analogue scales (VAS) for pain, a patellofemoral function scale (PFS), a step test and a subjective report of functional limitations. Measurements for each of the six components were taken on 56 PFPS patients participating in a randomized clinical trial, prior to and at one month following treatment. Modest test-retest reliability for the FIQ, VAS and step test were found. High internal consistency for the FIQ and modest internal consistency for the PFS were demonstrated. The VAS and FIQ were found to be good discriminators for measuring clinical change, while the step test was found to be reliable but poor at detecting clinical change. The PFS, which combines a number of evaluation areas into an index, demonstrated potential to detect clinical change, however, conclusions are limited as reliability testing was not performed.
Asunto(s)
Fémur/fisiopatología , Articulación de la Rodilla/fisiopatología , Evaluación de Resultado en la Atención de Salud , Manejo del Dolor , Modalidades de Fisioterapia , Actividades Cotidianas , Canadá , Femenino , Humanos , Actividades Recreativas , Masculino , Dolor/prevención & control , SíndromeRESUMEN
OBJECTIVE: To provide an overview of the investigational nuclear pharmacy service at the Medical University of South Carolina. DATA SOURCES: References were selected from published bibliographies of nuclear pharmacy and hospital pharmacy articles and from specific-topic searches of the MEDLINE computerized database (all languages, through 1992). STUDY SELECTION: Studies of clinical pharmacy functions that were considered relevant to the specialty practice of nuclear pharmacy were chosen. DATA EXTRACTION: Studies were reviewed for internal consistency and appropriateness. DATA SYNTHESIS: Data on the clinical impact of nuclear pharmacy services do not exist. CONCLUSIONS: Based on our experience in establishing an investigational drug service, we conclude that nuclear pharmacists should take an active role in clinical investigations. The outcomes of this kind of involvement are very rewarding.
Asunto(s)
Evaluación de Medicamentos/métodos , Drogas en Investigación , Servicio de Medicina Nuclear en Hospital/organización & administración , Servicio de Farmacia en Hospital/organización & administración , Control de Formularios y Registros , Hospitales con más de 500 Camas , Hospitales de Enseñanza/organización & administración , Humanos , Consentimiento Informado , Relaciones Interdepartamentales , Medicina Nuclear , Desarrollo de Programa/métodos , South CarolinaRESUMEN
In male Syrian hamsters daily evening melatonin injections resulted in increased circulating levels of growth hormone (GH), as well as a modest increase in body weight. A substantial increase in serum levels of insulin-like growth factor I (IGF-I) was observed in all hamsters receiving evening injections of melatonin for 10 weeks. The melatonin-induced increase in serum IGF-I levels was interpreted as a result of increased release of GH during the 10 week period of melatonin administration. The increase in serum GH and IGF-I was associated with significantly decreased hypothalamic turnover of norepinephrine (NE). Since blocking NE synthesis with alpha methyl-p-tyrosine reduced serum GH, the melatonin-induced increase in GH could not readily be attributed to decreased NE turnover. Highly significant increases in 5-hydroxyindole acetic acid (5HIAA) concentrations and in ratios of 5HIAA to serotonin (5HT) were noted in extracts of hypothalamus and in extracts of brain stem, suggesting a serotonergic component to melatonin-induced increase in GH-induced IGF secretion and subsequent growth.
Asunto(s)
Hormona del Crecimiento/sangre , Hipotálamo/fisiología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Melatonina/farmacología , Neurotransmisores/fisiología , Animales , Peso Corporal/efectos de los fármacos , Cricetinae , Ácido Hidroxiindolacético/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Inyecciones Subcutáneas , Masculino , Melatonina/administración & dosificación , Mesocricetus , Neurotransmisores/metabolismo , Norepinefrina/metabolismo , Serotonina/metabolismo , Testículo/efectos de los fármacos , Hormonas Tiroideas/metabolismoRESUMEN
We have shown in the companion paper that somatotrophs dispersed from streptozotocin diabetic rats exhibit altered sensitivity to the natural hypothalamic controlling hormones, growth hormone releasing factor and somatostatin. We have further studied the effects on growth hormone release from dispersed adenohypophysial cells of normal and streptozotocin diabetic rats of stimulation by compounds that increase cyclic 3',5'-adenosine monophosphate formation or inhibit its breakdown and of a phorbol ester. The cells of the diabetic rats had no change in sensitivity in response to either cholera toxin or forskolin. A phosphodiesterase inhibitor caused an equal GH release from cells of both diabetic and normal animals after 60 min of incubation. There was no change in sensitivity of the cells of diabetic animals or in the maximal response of these cells to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate when compared with normal cells. A low calcium medium that blocked growth hormone releasing factor stimulated growth hormone release from normal rat cells also blocked it from the cells of the diabetic rats. These results suggest that the defect in response of the somatotrophs of diabetic animals is specific and only occurs with the hypothalamic hormones and not with other secretagogues.
Asunto(s)
AMP Cíclico/metabolismo , Diabetes Mellitus Experimental/metabolismo , Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormona del Crecimiento/metabolismo , Adenohipófisis/metabolismo , Somatostatina/farmacología , Acetato de Tetradecanoilforbol/farmacología , 1-Metil-3-Isobutilxantina/farmacología , Animales , Toxina del Cólera/farmacología , Colforsina/farmacología , Relación Dosis-Respuesta a Droga , Masculino , Adenohipófisis/citología , Adenohipófisis/efectos de los fármacos , Ratas , Ratas EndogámicasRESUMEN
As growth hormone has been implicated in the "dawn phenomenon," an early morning rise in serum glucose, we have studied the control of growth hormone release in diabetes using an acutely dispersed system of adenohypophysial cells from normal or diabetic rats (65 mg/kg streptozotocin, 8 days before sacrifice; serum glucose, 490 +/- 17 mg/dL). Growth hormone release is normally controlled by the two hypothalamic hormones, growth hormone releasing factor and somatostatin. We have found cells of the diabetic rats exhibit changes in sensitivity that result in increased growth hormone release in static incubation. In normal cells, rat growth hormone releasing factor increases growth hormone release three- to four-fold with an EC50 of 151 +/- 27 pM (n = 7). In contrast, in cells from diabetic rats, there was a significant (twofold) increase in sensitivity to growth hormone releasing factor (EC50 = 75 +/- 15 pM, n = 7) which resulted in increased growth hormone release with lower but not maximal (10 nM) growth hormone releasing factor. Basal nonstimulated release was unchanged. Somatostatin inhibition of stimulated growth hormone release was reduced (n = 7); half-maximal inhibition occurred with 0.21 +/- 0.03 nM (normal) and 0.76 +/- 0.17 nM somatostatin (diabetic). In perifusion the peak secretion rate was significantly lower for diabetic cells stimulated by a maximal dose of growth hormone releasing factor. These studies suggest somatotrophs of diabetic rats have altered sensitivity in vitro to the controlling hormones growth hormone releasing factor and somatostatin.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormona del Crecimiento/metabolismo , Adenohipófisis/metabolismo , Somatostatina/farmacología , Animales , Técnicas In Vitro , Masculino , Adenohipófisis/citología , Adenohipófisis/efectos de los fármacos , Ratas , Ratas EndogámicasRESUMEN
Female Syrian hamsters maintained on a 14 h light, 10 h dark photoperiod were injected once daily (1-2 h before lights out) with melatonin (25 micrograms), alone or in combination with thiourea, or with thiourea plus thyroxine. Serum levels of the somatomedin, Insulin-like growth factor-I (IGF-I), were significantly reduced by thiourea as well as by melatonin administration. These data suggest that in the female hamster melatonin-induced reduction of circulating IGF-I depends largely on a reduction in circulating levels of thyroid hormones. However, melatonin-induced changes in secretion of thyroid hormones, gonadal hormones, and hypothalamic hormones could contribute to decreased growth hormone (GH)-stimulated somatomedin secretion.
Asunto(s)
Hipotiroidismo/sangre , Factor I del Crecimiento Similar a la Insulina/sangre , Melatonina/farmacología , Somatomedinas/sangre , Animales , Cricetinae , Oscuridad , Modelos Animales de Enfermedad , Combinación de Medicamentos , Femenino , Hormona del Crecimiento/sangre , Luz , Mesocricetus , Radioinmunoensayo , Tiourea/farmacología , Tiroxina/farmacología , Triyodotironina/sangre , Triyodotironina/fisiologíaRESUMEN
Male Syrian hamsters maintained on a 14-h light, 10-h dark photoperiod were injected once daily (1-2 h before lights out) with melatonin (25 micrograms), once every other day with T4 (5 micrograms every other day), or melatonin every day plus T4 every other day. Hamsters which received melatonin injections, with or without T4, had serum levels of insulin-like growth factor that were increased 2-fold. The results suggest that melatonin-induced changes in body weight are a result of long-term changes in insulin-like growth factor-I secretion.
Asunto(s)
Factor I del Crecimiento Similar a la Insulina/sangre , Melatonina/farmacología , Somatomedinas/sangre , Animales , Peso Corporal/efectos de los fármacos , Cricetinae , Hormona Luteinizante/sangre , Masculino , Mesocricetus , Análisis de Regresión , Tiroxina/farmacología , Triyodotironina/sangreRESUMEN
The secretion of GH, in vivo, is pulsatile. We have proposed that the timing of the episodic bursts of GH secretion is set by somatostatin (SRIF) withdrawal, while the magnitude of the bursts is set by the amount of GH-releasing factor (GRF) impinging on the somatotrophs, before and during SRIF withdrawal. We have now used an in vitro model of perifused rat pars distalis cells to further examine the interaction between GRF and SRIF on the magnitude of the burst of GH release that follows SRIF withdrawal. We first characterized the GH response, with time, to constant perifusion with GRF. The initial burst, followed by a rapid decrease in GH release induced by constant perifusion is due to a loss of GRF bioactivity in the perifusion medium and not to a decreasing responsiveness of the somatotrophs. This was followed by studies on the interaction between GRF and SRIF. The burst of GH release after cessation of perifusion with SRIF (10(-9) M) plus GRF (10(-10) M) can be blocked by the administration of SRIF during the burst. Also, the magnitude of the burst is proportional to the concentration of GRF preceding the withdrawal of SRIF. It is likely that similar relations apply in vivo, where SRIF withdrawal sets the timing and duration of the episodic burst of GH release, while GRF sets the magnitude.
Asunto(s)
Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormona del Crecimiento/metabolismo , Hipófisis/metabolismo , Proteínas Recombinantes/farmacología , Somatostatina/farmacología , Animales , Técnicas In Vitro , Cinética , Masculino , Hipófisis/efectos de los fármacos , RatasRESUMEN
TPA (12-O-tetradecanoylphorbol 13-acetate) is one of a class of compounds known as tumor promoters which perturb the inositol phosphate pathway in a number of cells. We have used TPA in a dispersed rat adenohypophysial cell system to probe the characteristics of growth hormone (GH) release. In this system we have found that the cells release GH in response to low concentrations of TPA: the EC50 was 0.23 +/- 0.05 nM (n = 6) and the maximal concentration was 5 nM. However, the maximal TPA-induced GH release was only 34 +/- 5% (n = 7) of the GH released by maximal growth hormone releasing factor (GRF) suggesting TPA releases a subpool of stored GH. Both somatostatin and insulin-like growth factor I inhibit GH release stimulated by TPA to the same extent as that stimulated by GRF, showing that the normal inhibitory control mechanism of release is not altered. Incubation in a low calcium medium that totally blocks GRF-stimulated GH release also inhibits TPA-stimulated GH release. The calcium channel blockers nifedipine and diltiazem both partly inhibit GRF- and TPA-stimulated GH release, showing some component of the calcium necessary for GH release arises from influx across the cell membrane.
Asunto(s)
Hormona Liberadora de Hormona del Crecimiento/farmacología , Factor I del Crecimiento Similar a la Insulina/farmacología , Somatomedinas/farmacología , Somatostatina/farmacología , Acetato de Tetradecanoilforbol/farmacología , Animales , Calcio/fisiología , Bloqueadores de los Canales de Calcio/farmacología , Células Cultivadas , Diltiazem/farmacología , Hormona del Crecimiento/metabolismo , Masculino , Nifedipino/farmacología , Adenohipófisis/fisiología , Ratas , Ratas EndogámicasRESUMEN
Growth hormone secretion is controlled by the two hypothalamic hormones, growth hormone releasing factor (GRF) and somatostatin. In addition, the insulin-like growth factors (IGF or somatomedins) which are themselves growth hormone dependent, inhibit growth hormone release in vitro, therefore acting to close the negative feedback loop. The studies reported here examine some of the differences between inhibition of growth hormone secretion by somatostatin and IGF-I in vitro. The major finding is that cycloheximide, a protein synthesis inhibitor, blocks inhibition of GRF-stimulated growth hormone release caused by IGF-I, without changing the inhibition caused by somatostatin. The experiments were done by exposing mixed rat adenohypophysial cells to secretagogues with or without cycloheximide for 24 h in a short term culture. Somatostatin (0.6 nM) totally blocked rat GRF (1 nM) stimulated growth hormone release to values 48% of control (nonstimulated values), while IGF-I (27 nM) only reduced the GRF-stimulated growth hormone release by 27 +/- 3% (N = 5). Cycloheximide (15 micrograms/mL) totally blocked the effect of IGF-I but not somatostatin. A low concentration (0.12 nM) of somatostatin, which only partly inhibited growth hormone release, was also unaffected by cycloheximide. In purified rat somatotrophs, somatostatin (0.1 nM) inhibited GRF-stimulated cAMP levels slightly and reduced growth hormone release while IGF-I (40 nM) had no effect. We suggest that IGF-I inhibits only the secretion of newly synthesized growth hormone, while somatostatin inhibits both stored and newly synthesized growth hormone pools.
Asunto(s)
Cicloheximida/farmacología , Hormona del Crecimiento/antagonistas & inhibidores , Factor I del Crecimiento Similar a la Insulina/farmacología , Adenohipófisis/metabolismo , Somatomedinas/farmacología , Somatostatina/farmacología , Animales , Hormona del Crecimiento/metabolismo , Hormona Liberadora de Hormona del Crecimiento/farmacología , Masculino , Adenohipófisis/efectos de los fármacos , Ratas , Ratas EndogámicasRESUMEN
IGFs are growth hormone-dependent, serum growth factors which are secreted primarily by liver, although other tissues contribute. We have measured IGF levels in serum of patients with primary biliary cirrhosis (n = 28), primary sclerosing cholangitis (n = 10), and alcohol-induced liver disease (n = 16), and compared them to a group of healthy controls (n = 25). Serum IGF-I as measured by radioimmunoassay was significantly decreased in all patient groups to 30% of control. After acid gel chromatography, IGF-II, measured by radioreceptor assay, was slightly decreased (p less than 0.05) in primary sclerosing cholangitis patients, but not in the other liver disease patients, when compared to the controls. The regression of IGF-II vs IGF-I for primary biliary cirrhosis patients was significant, with r = 0.62, p less than 0.01 (n = 27). The mean ratio of IGF-II/IGF-I was significantly different for histologic stage 2 vs stage 3 vs stage 4 primary biliary cirrhosis patients, but stage 2 was not different from control. We suggest low IGF-I values may reflect compromised hepatocyte function, and secretion of IGF-I and IGF-II may be from different cell populations, or controlled by different mechanisms.
Asunto(s)
Factor II del Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/sangre , Hepatopatías/sangre , Somatomedinas/sangre , Adulto , Anciano , Colangitis/sangre , Cromatografía en Gel , Femenino , Humanos , Cirrosis Hepática Biliar/sangre , Hepatopatías Alcohólicas/sangre , Masculino , Persona de Mediana Edad , RadioinmunoensayoRESUMEN
Growth hormone (GH) secretion is controlled by growth hormone releasing factor (GRF) but changes in the circulating level of this hormone are difficult to measure. Insulin-like growth factor (IGF-I) is a GH-dependent growth factor which significantly but slightly inhibits stimulated GH release in vitro. We have tested the effects of GRF and IGF-I on GH release in pregnancy, a state in which serum concentrations of GH are elevated and levels of IGF-I are lowered. We have found, in a system of acutely dispersed adenohypophysial cells prepared from pregnant (day 21-23) or control cycling female rats, that adenohypophysial cells from pregnant rats have an increased GH release with GRF. In contrast, IGF-I inhibition is similar but slightly smaller. These altered responses may result in elevated serum GH levels during pregnancy.
Asunto(s)
Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormona del Crecimiento/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Adenohipófisis/metabolismo , Preñez/fisiología , Somatomedinas/farmacología , Animales , Células Cultivadas , Femenino , Cinética , Adenohipófisis/efectos de los fármacos , Embarazo , Ratas , Ratas Endogámicas , Valores de Referencia , Somatostatina/farmacologíaRESUMEN
The secretion of GH is strikingly episodic. We have suggested that the timing of the episodic bursts of GH secretion is set by somatostatin (SRIF) withdrawal, whereas the magnitude of the bursts is determined by the amount of GH-releasing factor (GRF) impinging on the somatotrophs before and during SRIF withdrawal. We have now used an in vitro model of perifused rat pars distalis cells to examine the interaction of SRIF and GRF on GH release and, in particular, to examine the effect of GRF on the magnitude of the burst of GH release that follows SRIF withdrawal. After 30 min of perifusion with SRIF (10(-9) M), there follows an immediate but small burst of GH release. The burst of GH release following concurrent perifusion with SRIF plus GRF (10(-10) M) is increased, with a 7.5- to 9.5-fold increase in the peak secretion rate. When GRF is maintained after the withdrawal of SRIF, the peak secretion rate is not different from that seen after simple withdrawal of both SRIF and GRF, but the duration of the burst is increased. These data demonstrate that the presence of GRF during SRIF perifusion, while not altering basal release, does strikingly increase the post-SRIF release of GH. We propose that a similar relation applies in vivo, where SRIF withdrawal sets the timing of the episodic bursts of GH release, whereas GRF determines the magnitude.
Asunto(s)
Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormona del Crecimiento/metabolismo , Somatostatina/fisiología , Animales , Técnicas In Vitro , Masculino , Perfusión , Periodicidad , Adenohipófisis/efectos de los fármacos , Adenohipófisis/metabolismo , RatasRESUMEN
Somatomedins-insulin-like growth factors (SM/IGF) are growth hormone (GH) dependent serum growth factors. There is some evidence that IGF inhibit GH release (negative feedback) in 3- to 24-h incubations of cultured rat adenohypophysial cells. We have used acutely dispersed noncultured rat adenohypophysial cells to study the dynamics of IGF on GH secretion. In this system both IGF-I and IGF-II (100 ng/mL) slightly, but significantly, decrease the cumulative GH released by human pancreas growth hormone releasing factor 1-40 (GRF) and the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine. The inhibition is small (16%) and usually not statistically significant until 2 h of incubation. The inhibition with IGF is additive to that produced with low concentrations of somatostatin. The IGF also significantly decrease the rate of GH release in all time periods tested (0-1, 1-2, 2-3 h). In addition, the IGF decrease the quantity of [14C]leucine protein eluted at the position of labelled rat GH on Sephadex G75, which would include newly synthesized GH extracted from the cells. Thus we conclude that the decreased GH released may be due to an effect of IGF on both rate of release and on GH synthesis.
Asunto(s)
Hormona del Crecimiento/antagonistas & inhibidores , Somatomedinas/farmacología , 1-Metil-3-Isobutilxantina/farmacología , Animales , Hormona del Crecimiento/biosíntesis , Hormona del Crecimiento/metabolismo , Hormona Liberadora de Hormona del Crecimiento/farmacología , Humanos , Masculino , Fragmentos de Péptidos/farmacología , Adenohipófisis/citología , Adenohipófisis/metabolismo , Ratas , Ratas Endogámicas , Somatostatina/farmacología , Factores de TiempoRESUMEN
It has been reported that there is a striking homology between the basic insulin-like growth factors (IGF)-somatomedins (SM) found in humans and rats. The radioimmunoassay (RIA) developed for the human hormone IGF-I (basic somatomedin, B-SM) can measure immunoreactive IGF-I in rat serum (IrIGF-I). Using this RIA, the profile of serum IrIGF-I was measured at each day of gestation in groups of inbred and Charles River Wistar rats. In each case IrIGF-I showed a gradual increase in early and mid gestation followed by a sharp decrease that occurred late in gestation to values 20-40% of control. The profile obtained from Charles River Wistars was shifted in time compared with the inbred group. Neither ovariectomy nor progesterone administration to ovariectomized nonpregnant animals altered serum IrIGF-I levels. Thus, although rat IGF-I and human IGF-I can be measured using the same assay, the changes that occur in gestation are in opposite directions.
Asunto(s)
Factor I del Crecimiento Similar a la Insulina/sangre , Somatomedinas/sangre , Animales , Femenino , Masculino , Ovariectomía , Embarazo , Progesterona/farmacología , Radioinmunoensayo/métodos , Ratas , Ratas EndogámicasRESUMEN
The effects of 3 days of maternal ethanol administration on the placenta and on basic somatomedin (B-SM) were investigated in the mouse. Following administration of aqueous ethanol by gavage on days 13, 14 and 15 of gestation, there was no treatment-related difference in embyonic growth or placental weight as seen on day 15. There was a significant reduction in the specific binding of [125I]B-SM by day 15 placental membranes, but no difference in serum B-SM concentrations or in the frequency or severity of degenerative changes in the placenta. We have shown that changing levels of serum B-SM over the normal course of pregnancy correspond closely to patterns of cellular proliferation and aging in the placenta. It is possible that impairment in the binding activity of B-SM receptors contributes to the premature aging observed in term placentas exposed to alcohol during pregnancy in the rodent.
Asunto(s)
Etanol/farmacología , Trastornos del Espectro Alcohólico Fetal/metabolismo , Placenta/metabolismo , Somatomedinas/metabolismo , Animales , Femenino , Feto/metabolismo , Ratones , Ratones Endogámicos DBA , Microsomas/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Unión Proteica , Reproducción/efectos de los fármacosRESUMEN
An acutely dispersed and purified preparation of somatotrophs obtained from rat adenohypophyses was used to study the mechanism of action of GH-releasing factor (GRF). Synthetic GRF [human pancreatic, hpGRF-(1-40)-OH] stimulated the immediate (within 4 min) release of GH in a dose-related manner, with a preceding or concurrent increase in cAMP in the somatotrophs. Somatostatin, at concentrations as low as 1.0 ng/ml, completely blocked the GRF-induced increase in GH release, with only a partial reduction in the GRF-induced accumulation of cAMP in the somatotrophs. 3-Isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, potentiated the action of GRF in increasing cAMP in the somatotrophs, with subsequent GH release. These results along with those of previous studies suggest that cAMP is an intracellular mediator in the action of GRF and that somatostatin has a major effect on blocking GH release at a step subsequent to cAMP accumulation.
Asunto(s)
AMP Cíclico/metabolismo , Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormona del Crecimiento/metabolismo , Somatostatina/farmacología , 1-Metil-3-Isobutilxantina/farmacología , Animales , GMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Masculino , Adenohipófisis/efectos de los fármacos , Adenohipófisis/metabolismo , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
Basic somatomedin (B-SM) like insulin-like growth factor-I or somatomedin-C belongs to the basic group of somatomedins. In preliminary studies on the control system for B-SM, we have found that plasma levels of immunoreactive B-SM (IRSM) fluctuate in conscious adult male rats. The peaks average 85% of the local baseline level (minimum of 6 points) and occur with an interpeak interval of 2.1 h. In rats anaesthetized with nembutal (50 mg/kg) very few peaks were found. After approximately 3.4 hr. of anaesthesia, plasma IRSM levels dropped precipitously with a calculated T1/2 of 50 minutes. These results suggest that IRSM levels may be related to serum CH levels which occurred 4 hr previously and that part of variation seen in serum levels in conscious rodents may be due to physiological fluctuations.
Asunto(s)
Anestesia , Somatomedinas/sangre , Animales , Ritmo Circadiano , Hormona del Crecimiento/sangre , Hormona Liberadora de Hormona del Crecimiento/farmacología , Factor I del Crecimiento Similar a la Insulina , Masculino , Ratones , Pentobarbital/farmacología , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
Gap junctions between pancreatic beta-cells were quantitatively assessed in freeze-fracture replicas of isolated rat islets of Langerhans incubated for 90 min with or without the potassium conductance blocker tetraethylammonium (TEA). The results show that TEA increases the median number of particles per beta-cell gap junction but not the frequency of gap junctions at both nonstimulating and threshold-stimulating concentrations of glucose. TEA increased the relative gap junctional area at both concentrations of glucose. TEA had no effect on insulin release at a basal concentration of glucose but potentiated that release at the threshold glucose level. Thus TEA modifies beta-cell gap junctions independently of its effect on insulin release. However, the junctional changes observed were greater when insulin release was also elevated.