Acute effects of aerobic exercise on mood.

32 female medical students (aged 18–23 yrs) completed 2 8-min trials of high-intensity exercise and 2 8-min trials of low-intensity exercise. One high- and 1 low-exercise trial were accompanied by music; the other 2 trials were accompanied by metronome. Mood was assessed with a modification of the Profile of Mood States before and immediately after each trial. Ss were divided into fit and unfit groups based on heart rate responses during high-exercise trials. High-intensity exercise led to increases in tension/anxiety and fatigue, whereas positive mood changes (vigor and exhilaration) were seen following low-intensity exercise only. No fitness group differences in mood responses were observed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute effects of qigong exercise on mood and anxiety.

Psychosocial stress may lead to increased rates of anxiety and depression. Aerobic exercise and mind-body therapies are frequently described as having positive effects on psychological well-being by enhancing mood and reducing anxiety. Few studies, however, have investigated the acute psychological effects of qigong exercise. Fifty-nine regular qigong exercisers (mean age 50.8 years) were randomized to a Qigong or Control group. Pre- and postmeasurements were then compared. POMS-Depression, Anger, and Fatigue, and STAI-State Anxiety scores decreased significantly in the Qigong group but not in the Control group. Results thereby suggest that qigong exercise can produce desirable psychological effects, and Qigong exercise may therefore be included among other activities performed to boost resistance to daily stressors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute and delayed effects of prolonged exercise on serum lipoproteins. II. Concentration and composition of low-density lipoprotein subfractions and very low-density lipoproteins

To investigate the effects of a single period of prolonged exercise on lipoprotein concentration and composition, 13 healthy endurance-trained men were examined before and after (1 h, 20 h) a cross-country run [30 km, time: 130 (SD 7.4) min]. The data show that following acute exercise, serum triglyceride (TG) concentration were reduced (36%) as a consequence of a reduced number (31%) of very low density lipoprotein (VLDL) particles. Changes in composition of VLDL were present but less evident. In contrast to this, acute exercise did not induce significant changes in the average concentration of individual low-density lipoprotein (LDL) subfractions. However, changes in dense LDL [density (d) > 1.044 g.ml-1] concentration were significantly correlated to changes in serum TG: a reduction of dense LDL occurred in subjects with large reductions in serum TG. In addition, LDL composition changed significantly. Immediately (1 h) after exercise the TG content of all LDL subfractions was reduced. These reductions were significant in large (d = 1.006-1.037 g.ml-1) and small LDL (1.044-1.063 g.ml-1). It can be concluded therefore from our study that acute exercise primarily altered the composition of LDL subfractions while their concentration remained stable.     

Acute effects of exercise or sauna on appetite in obese and nonobese men

To study the effect of exercise on appetite in men, hunger, thirst, taste perception, energy intake, and macronutrient choice were assessed in relation to exercise and to sauna; the latter was done to correct for dehydration and rise in body temperature. Since exercise is used to prevent and cure obesity, subjects included obese as well as nonobese men. Thirty subjects (25 +/- 7 years, BMI 22.8 +/- 1.6 and 28.5 +/- 1.9) were given twice, in random order before and after 2 h of cycling at 60% of Wmax, 2 h of sauna, or 2 h of rest, an ample choice from solid and liquid almost single-macronutrient food items and a taste perception test with solutions of sucrose, citric acid, NaCl, quinine, a mixture of these, and a carbohydrate electrolyte solution. After cycling as well as after sauna, in comparison to after rest, subjects lost 3 +/- 0.5% of body mass, while thirst, fluid intake, perception of sweet at relatively low concentrations, and percentage of energy coming from carbohydrate increased significantly. Only after cycling compared to after rest did perception of bitterness at a low concentration increase and hunger and energy intake decrease. We conclude that exercise induced a short-term reduction in hunger and energy intake, whereas exercise and sauna induced a short-term increase in taste perception of sweet at the lower concentration, while macronutrient preference of carbohydrate increased.     

Acute effects of cocaine on human brain activity and emotion

We investigated brain circuitry mediating cocaine-induced euphoria and craving using functional MRI (fMRI). During double-blind cocaine (0.6 mg/kg) and saline infusions in cocaine-dependent subjects, the entire brain was imaged for 5 min before and 13 min after infusion while subjects rated scales for rush, high, low, and craving. Cocaine induced focal signal increases in nucleus accumbens/subcallosal cortex (NAc/SCC), caudate, putamen, basal forebrain, thalamus, insula, hippocampus, parahippocampal gyrus, cingulate, lateral prefrontal and temporal cortices, parietal cortex, striate/extrastriate cortices, ventral tegmentum, and pons and produced signal decreases in amygdala, temporal pole, and medial frontal cortex. Saline produced few positive or negative activations, which were localized to lateral prefrontal cortex and temporo-occipital cortex. Subjects who underwent repeat studies showed good replication of the regional fMRI activation pattern following cocaine and saline infusions, with activations on saline retest that might reflect expectancy. Brain regions that exhibited early and short duration signal maxima showed a higher correlation with rush ratings. These included the ventral tegmentum, pons, basal forebrain, caudate, cingulate, and most regions of lateral prefrontal cortex. In contrast, regions that demonstrated early but sustained signal maxima were more correlated with craving than with rush ratings; such regions included the NAc/SCC, right parahippocampal gyrus, and some regions of lateral prefrontal cortex. Sustained negative signal change was noted in the amygdala, which correlated with craving ratings. Our data demonstrate the ability of fMRI to map dynamic patterns of brain activation following cocaine infusion in cocaine-dependent subjects and provide evidence of dynamically changing brain networks associated with cocaine-induced euphoria and cocaine-induced craving.     

Acute effects of estradiol infusion and naloxone on luteinizing hormone secretion in pubertal boys

We have shown previously in pubertal boys that testosterone (T) suppresses the nocturnal augmentation of luteinizing hormone (LH) secretion principally by decreasing LH pulse frequency. As T can be aromatised to estradiol (E2), and E2 effects on LH secretory dynamics may be separate from those of T, we examined the effects of acute E2 infusion on LH secretion in pubertal boys. Opioid receptor blockade has been reported to increase LH secretion after estradiol suppression in adult men, so we also examined whether naloxone might augment LH secretion during E2 treatment in pubertal boys. Starting at 1000 h, eight pubertal boys were given a 33 h saline infusion, followed 1 week later by an E2 infusion at 4.6 nmol/m2/h. During both infusions, four iv boluses of saline were given hourly beginning at 1200 h on the first day, and four naloxone iv boluses, 0.1 mg/kg each, were given hourly beginning at 1200 h on the second day. Blood was obtained every 15 min for LH, and every 60 min for T and E2, from 1200 h until the end of the infusion. Pituitary responsiveness to gonadotropin-releasing hormone (GnRH) was assessed after both infusions by iv administration of 250 ng/kg synthetic GnRH. Estradiol infusion increased the mean plasma E2 concentration from 23 +/- 4 to 46 +/- 6 pmol/L (P < 0.01) and suppressed mean plasma T from 4.9 +/- 1.4 to 3.0 +/- 3.5 nmol/L (saline vs. E2 infusion, P < 0.05). The overall mean LH was suppressed by E2 infusion from 3.7 +/- 0.5 to 2.2 +/- 0.4 IU/L (saline vs. E2 infusion, P < 0.01). LH pulse frequency was suppressed by 50%, whereas mean LH pulse amplitude was not different between saline and E2 infusions. Administration of naloxone did not alter the mean LH, LH pulse frequency, or amplitude during either saline or E2 infusions. Pituitary responsiveness to exogenous GnRH was similar during both infusions. These studies indicate that E2 produces its negative feedback in pubertal boys principally by suppression of LH pulse frequency, and naloxone does not reverse these suppressive effects. Thus E2 suppression of LH secretion is mediated by a decrease of hypothalamic GnRH secretion that is independent of endogenous opioid pathways.     

Inhibition of melatonin secretion by ethanol in man

To determine whether ethanol inhibits nocturnal melatonin (MT) secretion, three experiments (A, B, and C) were performed in seven normal subjects. In A, ethanol at a dose of 0.34 g/kg was administered orally at 6:00, 8:00, and 10:00 PM. Each dose was increased to 0.52 g/kg in B. In C, water was substituted for ethanol. Blood samples for determination of serum MT levels were drawn every second hour between 6:00 PM and 8:00 AM. Urinary excretion of MT during the night was also determined. In A, serum ethanol reached a maximal level of 13 +/- 1 mmol/L at 12 midnight. In B, the corresponding maximum was 25 +/- 1 mmol/L. The higher alcohol dose inhibited nocturnal MT secretion by 20% +/- 5% (P < .01), whereas the lower dose lacked such effect. Urinary excretion of MT was left unaffected by alcohol at both doses. Five additional normal subjects were given alcohol as described above at a dose of 0.52 g/kg (experiment D). This induced mild nocturnal hypoglycemia as evidenced by a glucose decremental area (5.9 +/- 1.8 mmol/L.h) that differed significantly from zero (P < .05). To determine whether a reduced glucose delivery to pinealocytes might contribute to the decreased MT secretion in alcohol-intoxicated subjects, two experiments (E and F) were performed in eight healthy individuals. In E, ethanol was given orally as in B; three small oral doses of glucose were also given at 8:00 PM, 10:00 PM, and 12 midnight. In F, water was substituted for ethanol and glucose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circadian secretion patterns of melatonin after major surgery

Despite our advances in the diagnosis and treatment of asthma, the incidence of mortality is increasing in developed countries. As patients and health care providers seek new options for the treatment and prevention of asthma, various complementary and alternative medical therapies are being used. With funding from the Office of Alternative Medicine, National Institutes of Health, our goal was to identify the type and prevalence of complementary and alternative treatments for asthma in use in the United States in order to establish a research agenda for the study of the most promising therapies. A survey was developed by an expert panel. After undergoing a preliminary round of testing and improvement, the survey was then sent along with a postage-paid return envelope as inserts in the May 1996 issue of Alternative Therapies in Health and Medicine, a peer-reviewed periodical of complementary and alternative medical research and scholarly activity; 10,000 surveys were distributed. We asked that only those who treated asthma respond. The surveys were designed to identify characteristics of the respondent, their particular practice type, use of complementary and alternative medicine, or conventional medicine in general, patient characteristics and numbers, and their use of 20 specific potential therapies to treat asthma. A total of 564 surveys were returned. The 5.64% response rate was low but was reflective of the demographics of the readership of this journal of complementary and alternative medicine. The survey population was 46% male and 43% female; 11% did not specify gender. They ranged in age from under 31 years old to over 70. The largest group (37%) of respondents held degrees as medical doctors, 27% held doctorates in complementary and alternative medicine related disciplines, 11% had registered nursing degrees, 4% were acupuncturists and 18% did not specify their training. Practice characteristics between MD and non-MD asthma care providers did not differ. The majority had general practices (75%) seeing all ages of patients. MDs were less likely to employ complementary and alternative medicine techniques for asthma compared to non-MDs. Both groups identified dietary and nutritional approaches as their most prevalent and useful asthma treatment option. Use of botanicals, meditation and homeopathy were frequently cited; statistically significant differences appeared in the rankings of treatment usefulness and prevalence between MD and non-MDs. Non-MD asthma care providers were more likely to ask patients about their use of complementary and alternative treatments for asthma than MDs (92% vs. 70%), while both groups showed statistically significant increases in their levels of patient inquiries compared to 2 years previously (up 9% and 8% for MDs and non-MDs respectively). The predominance of diet and nutrition supplementation used by MDs and non-MDs suggests that further attention and research efforts should be directed toward this area of complementary and alternative practice. Other complementary and alternative medicine practices such as botanicals, meditation and homeopathy appear to warrant research efforts. Differences between MDs and non-MDs in their use of such therapies may reflect different philosophies as well as training.     

Diurnal melatonin and cortisol secretion profiles in medicated schizophrenic patients

Although melatonin and/or cortisol secretions have been suggested as markers for both circadian and noradrenaline dysfunctions in psychiatric illnesses, especially in affective disorders, studies of melatonin and cortisol in schizophrenic patients are rare. We evaluated the circadian profiles of melatonin and cortisol secretion in schizophrenic patients and control subjects. A total of 21 medicated Taiwanese male paranoid schizophrenic inpatients (mean age, 27.3 +/- 7.2 yr) and 21 age- and sex-matched controls underwent 24-hour neuroendocrine screening. Melatonin and cortisol concentrations were measured at 2-hour intervals from 0800 h to 2200 h, and at 1-hour intervals from 2300 h to 0700 h. The standard dexamethasone suppression test was performed the next day to provide an index of hypothalamic-pituitary-adrenal axis (HPA) function. The results showed that the circadian rhythm of plasma melatonin secretion was disrupted in schizophrenics compared with controls, whereas the 24-hour profile of plasma cortisol was preserved. The melatonin to cortisol ratio was significantly higher in control subjects than in schizophrenic patients. Results of the dexamethasone suppression tests indicated that there were no functional changes in the HPA axis in schizophrenic patients. Five drug-naive schizophrenic patients studied simultaneously, but whose data were not included in the above analyses, had results consistent with those of the maintenance-medicated patients. Our findings suggest the presence of abnormal melatonin metabolism in Taiwanese schizophrenics, which may possibly be related to the pathophysiologic process itself. However, broader pathogenetic aspects of these neuroendocrine interrelations remain to be clarified.     

Acute and chronic effects of ethanol on fluid transport in the human small intestine

The effect of acute and chronic administration of ethanol on jejunal and ileal water and electrolyte transport was studied in healthy volunteers by the triple lumen intestinal perfusion technique. The acute perfusion of a glucose-free electrolyte solution containing 2 to 10 g per 100 ml of ethanol in the jejunum or ileum did not cause any significant alterations of sodium or water transport. In contrast, the administration of a folate-deficient diet and ethanol for 2 weeks produced a marked reduction in sodium and water absorption or a small net secretion (control, mean +/-SE: H2O = 0.91 +/- 0.06 ml per min, Na = 130 +/- 8 micronEq per min per 30 cm of intestine versus H2O = -0.13 +/- 0.14 ml per min, Na = -20 +/- 29 micronEq per min per 30 cm, P less than 0.001). These changes were not accompanied by a reduction in serum folate levels. The administration of ethanol with a folate-supplemented diet also produced significant but less pronounced changes in sodium and water transport control: H2O = 1.33 +/- 0.2 ml per min, Na = 185 +/- 34 micronEq per min per 30 cm of intestine versus H2O = 0.48 +/- 0.17 ml per min, Na =65 +/- 16 micronEq per min per 30 cm of intestine, P less than 0.05). From this study it appears that the diarrhea seen in chronic alcoholics can be explained in part by the effect of ethanol on intestinal sodium transport, without any accompanying changes in serum folate levels.     

Central nervous system action of melatonin on gastric acid and pepsin secretion in pylorus-ligated rats

We recently demonstrated that centrally administered melatonin at low doses inhibits the induction of gastric lesions by water-immersion restraint stress. To investigate the mechanism of the potent anti-ulcer action of melatonin, the central nervous system (CNS) effects of melatonin on gastric acid and pepsin secretion were studied in conscious pylorus-ligated rats. Intracisternal (i.c.) melatonin (1-100 ng) dose-dependently decreased acid and pepsin output, while a higher i.p. dose (1 microg) had no inhibitory effect. The i.c. melatonin did not change serum gastrin concentrations. Serum melatonin concentrations at 1 and 4 h after i.c. administration of 10-100 ng melatonin did not differ from those in rats receiving i.c. vehicle. The present results suggest that melatonin administered centrally modulates the secretion of gastric acid and pepsin which may explain, at least in part, the protective, anti-stress role of melatonin in the gastric mucosa observed in our previous study.     

Acute effects of dietary fatty acids on the fatty acids of human milk

1. Effects on 5-HT function of sibutramine and its active metabolites, BTS 54 354 and BTS 54 505, were compared with fluoxetine, (+)-fenfluramine and (+)-amphetamine. 2. In vitro sibutramine weakly inhibited [3H]-5-HT uptake into brain synaptosomes. BTS 54 354, BTS 54 505 and fluoxetine were powerful [3H]-5-HT uptake inhibitors, whereas (+)-fenfluramine and (+)-amphetamine were very much weaker. Conversely, whilst sibutramine, its metabolites and fluoxetine did not release [3H]-5-HT from brain slices at < or = 10(-5)M, (+)-fenfluramine and (+)-amphetamine concentration-dependently increased [3H]-5-HT release. 3. Sibutramine and fluoxetine had no effect on 5-hydroxytryptophan (5-HTP) accumulation in either frontal cortex or hypothalamus at doses < 10 mg kg(-1). In contrast, (+)-amphetamine ( > or = 3 mg kg(-1)) reduced 5-HTP in hypothalamus, whilst (+)-fenfluramine (> or =1 mg kg(-1)) decreased 5-HTP in both regions. 4. Sibutramine (10 mg kg(-1) i.p.) and fluoxetine (10 mg kg(-1) i.p.) produced slow, prolonged increases of extracellular 5-HT in the anterior hypothalamus. In contrast, (+)-fenfluramine (3 mg kg(-1) i.p.) and (+)-amphetamine (4 mg kg(-1) i.p.) induced rapid, short-lasting increases in extracellular 5-HT. 5. Only (+)-fenfluramine (10 mg kg(-1)) altered 5-HT2A receptors in rat frontal cortex when given for 14 days, producing a 61% reduction in receptor number and a 18% decrease in radioligand affinity. 6. These results show that sibutramine powerfully enhances central 5-HT function via its secondary and primary amine metabolites; this effect, like that of fluoxetine, is almost certainly mediated through 5-HT uptake inhibition. By contrast, (+)-fenfluramine enhances 5-HT function predominantly by increasing 5-HT release. (+)-Amphetamine, though weaker than (+)-fenfluramine, also enhances 5-HT function by release.     

Lack of melatonin effects on insulin action in normal rats

Despite a large number of studies, the role of melatonin on glucose metabolism is still controversial. The aim of the present work was to further characterize the effect of melatonin on insulin action during: i) intravenous insulin tolerance test performed at different times of the day using melatonin, a melatonin agonist (S-20304), a melatonin antagonist (S-20928) or in pinealectomized rats. ii) euglycemic-hyperinsulinemic clamp performed in melatonin agonist-treated as well as in pinealectomized rats. The fall in glycemia after the insulin injection was not significantly affected by melatonin and melatonin agonist (S-20304) at ZT6, nor by the melatonin antagonist (S-20928) at ZT13 nor in pinealectomized animals at ZT6 in comparison to their respective control. Acute treatment with S-20304 or chronic suppression of melatonin by pinealectomy did not significantly alter basal plasma glucose and insulin levels or hepatic glucose production and whole body or individual tissue glucose utilization. These data do not give support to a crucial role of melatonin on insulin action in normal rats.     

Studies of melatonin effects on epithelia using the human embryonic kidney-293 (HEK-293) cell line

The expression of melatonin receptors (MR) of the Mel1a subtype in basolateral membrane of guinea pig kidney proximal tubule suggests that melatonin plays a role in regulating epithelial functions. To investigate the cellular basis of melatonin action on epithelia, we sought to establish an appropriate in vitro culture model. Epithelial cell lines originating from kidneys of dog (MDCK), pig (LLC-PK1), opossum (OK), and human embryo (HEK-293) were each tested for the presence of MR using 2-[125I]iodomelatonin (125I-MEL) as a radioligand. The HEK-293 cell line exhibited the highest specific 125I-MEL binding. By intermediate filament characterization, the HEK-293 cells were determined to be of epithelial origin. Binding of 125I-MEL in HEK-293 cells demonstrated saturability, reversibility, and high specificity with an equilibrium dissociation constant (Kd) value of 23.8 +/- 0.5 pM and a maximum number of binding sites (Bmax) value of 1.17 +/- 0.11 fmol/mg protein (n = 5), which are comparable with the reported Kd and Bmax values in human kidney cortex. Coincubation with GTPgammaS (10 microM) and pertussis toxin (100 ng/ml) provoked a marked decrease in binding affinity (Kd was increased by a factor of 1.5-2.0), with no significant difference in Bmax. Melatonin (1 microM) decreased the forskolin (10 microM) stimulated cAMP level by 50%. HEK-293 cells do not express dopamine D1A receptor. Following transient transfection of HEK-293 cells with human dopamine D1A receptor (hD1A-R), exposure of the cells to dopamine stimulated an increase in the level of cAMP. Similarly, transient transfection of HEK-293 cells with rat glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and PTH type 1 receptors, each resulted in an hormone inducible increase in cAMP levels. Surprisingly, only the stimulatory effect of dopamine could be inhibited by exposure to melatonin. The inhibitory effect of melatonin on dopamine D1-induced increase in cAMP was completely inhibited by pertussis toxin (100 ng/ml, 18 h). Immunoblot and immunocytochemical studies were carried out using two polyclonal antibodies raised against the extra and cytoplasmic domains of Mel1a receptor. Immunoblot studies using antibody against the cytoplasmic domain of Mel1a receptor confirmed the presence of a peptide blockable 37 kDa band in HEK-293 cells. Indirect immunofluorescent studies with both antibodies revealed staining predominantly at the cell surface, but staining with the antibody directed against the cytoplasmic domain required prior cell permeabilization. By RT-PCR, HEK-293 cells express both Mel1a and Mel1b messenger RNAs, but the messenger RNA level for Mel1b is several orders of magnitude lower than for Mel1a. We conclude that HEK-293 cells express MR predominantly of the Mel1a subtype. Our evidence suggests that one of the ways that melatonin exerts its biological function is through modulation of cellular dopaminergic responses.     

Acute and delayed cerebral infarction after wasp sting anaphylaxis

Mutations and overexpression of p53 gene in prostate carcinoma have been found but their significance in the development and progression of cancer is so far unknown. We investigated the prevalence of abnormalities of p53 protein in a heterogeneous group of prostate carcinoma to verify whether acinar and non acinar carcinomas have a different expression of p53 protein. Paraffin sections of 45 prostate carcinomas (39 acinar, 3 ductal papillary, 1 transitional cell, 1 mucinous and 1 pure small cell) were examined for the expression of p53 protein using a panel of antibodies (monoclonal antibodies Pab 1801, D07 and polyclonal antibody CM1). No p53 expression was observed in any acinar carcinomas independent of grade and stage. For non acinar carcinomas only small cell and transitional cell carcinomas exhibited detectable amounts of p53 protein in tumour cell nuclei. The prevalence of p53 overexpression in prostate carcinoma is relatively low compared with that found in many other tumours. In the present study, the overexpression of p53 in a small cell carcinoma and in a transitional cell carcinoma suggest that the loss of suppressing role of p53 gene may be an important mechanism in the genesis and in the development of these uncommon tumours.     

Exogenous melatonin fails to counteract the light-induced phase delay of human melatonin rhythm

HIV-1, subtype F was isolated from a seronegative child aged 2.5 yr. ELISA tests (Behring HIV-1 + 2, Abbott HIV-1 + 2, Wellcozyme HIV-1 Recombinant, Clonatec HIV-1 + 2, Genelavia Mixt), and also rapid tests (Abbott Pack, Serodia) were all negative, although some of them presented borderline reactivities. Western Blot (Cambridge Biotech) revealed an undetermined profile (traces of anti-gp160 plus anti-p24). A new WB test (Sanofi Dg. Pasteur) performed at a higher serum concentration (1/25) revealed a complete antibody profile, despite the very low intensity of bands. A new serum sample prelevated 6 month later was completely negative on all tests used. Both samples, were negatives in WB for HIV2 and HTLVs. A heparinised blood sample was used for the co-cultivation of PBMC and was proven to be positive in the 14th day of culture. The isolated DNA from end-culture cells was subjected to PCR amplifications for Heteroduplex Mobility Assay direct subtyping (primers ES7 and ES8) and for the investigation of genotypic sensitivity to AZT (primers A/NE1). Lymphocyte populations phenotyping revealed leukocytosis (> 15,000/mL) with a predominance of the CD8+ subset CD4/CD8 ratio was < 1. Plasmatic HIV-1 load (measured by bDNA--Chiron) did not reached detectable levels of HIV-1 RNA. p24 Ag assay (EIA-Coulter) revealed a detectable p24 antigenemia only in the first serum sample and only after acid dissociation. So, this patient may present an integrated HIV-1 infection until now "silent".     

Concentration-dependent effects of adrenaline on the profile of insulin secretion from isolated human islets of Langerhans

The effects of the mixed alpha/beta-agonist adrenaline on insulin secretion from isolated human islets of Langerhans were studied. In static incubation experiments, adrenaline (0.1 nmol/l to 10 mumol/l) caused a concentration-dependent inhibition of glucose-induced insulin secretion from isolated human islets. However, perifusion experiments revealed that the time-course of the secretory changes induced by adrenaline was complex. When employed at a high concentration (1 mumol/l), adrenaline caused a sustained inhibition of glucose-induced insulin secretion, which could be relieved by the addition of the alpha 2-antagonist yohimbine (10 mumol/l). By contrast, infusion of adrenaline at a lower concentration (10 nmol/l), produced a large initial potentiation of glucose-induced insulin secretion. This response was, however, short-lived and followed by sustained inhibition of secretion, which could be relieved by yohimbine (10 mumol/l). The initial stimulation of insulin secretion provoked by 10 nmol adrenaline/l was abolished when islets were incubated in the presence of the beta-antagonist, propranolol (1 mumol/l), consistent with activation of beta-adrenoceptors. In support of this, treatment of human islets with the selective beta 2-agonist clenbuterol, was also associated with marked stimulation of insulin secretion. By contrast, each of two selective beta 3-agonists tested failed to alter insulin secretion from human islets. The results indicate that human pancreatic B-cells are equipped with both alpha 2- and beta 2-adrenoceptors which can affect insulin secretion. Adrenaline interacts with both of these but the alpha 2-response is predominant and can overcome the tendency of beta 2-adrenoceptors to potentiate insulin release.