High intake of dietary tyramine does not deteriorate glucose handling and does not cause adverse cardiovascular effects in mice

Tyramine is naturally occurring in food and induces pressor responses. Low-tyramine diets are recommended for patients treated with MAO inhibitors to avoid the fatal hypertensive crisis sadly known as "cheese effect". Hence, tyramine intake is suspected to have toxicological consequences in humans, while its administration to type 1 diabetic rodents has been reported to improve glucose tolerance. We investigated in mice whether prolonged tyramine ingestion could alter glucose homeostasis, insulin sensitivity, adipose tissue physiology or cardiovascular functions. Tyramine was added at 0.04 or 0.14 % in the drinking water since this was estimated to increase by 10- to 40-fold the spontaneous tyramine intake of control mice fed a standard diet. Ten to 12 weeks of such tyramine supplementation did not influence body weight gain, adiposity or food consumption. Both doses (reaching approx. 300 and 1100 μmol tyramine/kg bw/day) decreased nonfasting blood glucose but did not modify glucose tolerance or fasting levels of glucose, insulin or circulating lipids. Blood pressure was not increased in tyramine-drinking mice, while only the higher tested dose moderately increased heart rate without change in its variability. Markers of cardiac tissue injury or oxidative stress remained unaltered, except an increased hydrogen peroxide production in heart preparations. In isolated adipocytes, tyramine inhibited lipolysis similarly in treated and control groups, as did insulin. The lack of serious adverse cardiovascular effects of prolonged tyramine supplementation in normoglycemic mice together with the somewhat insulin-like effects found on adipose cells should lead to reconsider favourably the risk/benefit ratio of the intake of this dietary amine (AU)

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Dietary fibre: influence on body weight, glycemic control and plasma cholesterol profile / Fibra dietética: influencia sobre el peso corporal, el control glicémico y el perfil del colesterol plasmático

There have been several studies on the effects of dietary fibre on the metabolism. Epidemiologic studies have consistently reported an inverse relationship between dietary fibre and type 2 diabetes mellitus or cardiovascular mortality. This review focuses on observational and experimental studies that examine the effect of different types and sources of dietary fibre on body weight, glucose metabolism and lipid profile. From the available evidence, we conclude that clinical studies consistently show that the intake of viscous dietary fibre decreases the low density lipoprotein cholesterol and postprandial glucose levels, and induces short term satiety. However, few clinical trials have demonstrated that the intake of dietary fibre has a positive effect on the control of diabetes and body weight (AU)

Existen diversos estudios que han evaluado el efecto del consumo de fibra dietética sobre el metabolismo. Diversos estudios epidemiológicos observaron una relación inversa entre la fibra dietética y la diabetes mellitus tipo 2 o la mortalidad cardiovascular. Esta revisión se basa sobre estudios observacionales y experimentales que han valorado los efectos de diferentes tipos y fuentes de fibra dietética sobre el peso corporal, el metabolismo de la glucosa y el perfil lipídico. De la evidencia disponible, concluimos que los estudios clínicos consistentemente muestran que la ingesta de alimentos fuentes de fibra viscosa disminuye el colesterol de las lipoproteínas de baja densidad y los niveles de glucosa postprandial e induce la saciedad a corto plazo. Sin embargo, pocos ensayos clínicos han demostrado un efecto positivo sobre el control de la diabetes y el peso corporal (AU)

Glucose and erythrocyte ATP: distinctive effects of dipyridamole and of ticlopidine.

This experiment suggests the following points: 1. Erythrocytes in control patients and in atherosclerosis patients seem to have a variable grade of affinity for adenosine and for plasma glucose. This variable grade seems to fix the level of the adenosine triphosphate (ATP) reserves and induces the erythrocytes' deformability. 2. The drop in the level of ATP reserves that induces the poor deformability of the erythrocytes in atherosclerosis patients would appear to be caused by two consecutive shortages: first a shortage that seems to be related to a deficiency of erythrocyte adenosine as the ATP shortage disappears with dipyridamole treatment and then a shortage induced by the lack of erythrocyte glucose and suppressed by the addition of ticlopidine to the dipyridamole treatment.

Diabetes mellitus and thermoregulation.

Diabetes mellitus is accompanied by a variety of alterations in metabolic, cardiovascular, and neuronal function. This paper provides a comprehensive review of the ways in which these pathophysiological aspects of diabetes may impair thermoregulatory function. The influence of diabetic neuropathy and vasculopathy on the control of peripheral blood flow is reviewed and the additional effects of changing levels of blood glucose and insulin are discussed. Both hypoglycaemia and diabetic ketoacidosis are associated with hypothermia, but the reasons for this in ketoacidosis are not clear. Impairment of heat conservation may contribute to and could be a consequence of autonomic neuropathy. The final section of the paper describes a study of our own in which metabolic stability was maintained by infusing insulin intravenously before and during the determination of the thermoregulatory responses to acute cold stress. Under these conditions, there was impairment of reflex vasoconstriction in the limbs of diabetics with neuropathy. This failure to reduce heat loss resulted in half the diabetics with neuropathy shivering in response to moderate cooling, which in some subjects was accompanied by a fall in core temperature. Diabetics without neuropathy and nondiabetics neither shivered nor dropped core temperature.

Effect of oral glucose administration on plasma growth hormone-releasing hormone (GHRH)-like immunoreactivity levels in normal subjects and patients with idiopathic GH deficiency: evidence that GHRH is released not only from the hypothalamus but also from extrahypothalamic tissue.

Using a specific and sensitive RIA for GH-releasing hormone (GHRH), we examined the effect of oral administration of 75 g glucose on peripheral plasma GHRH-like immunoreactivity (GHRH-LI) in normal subjects (n = 12) and patients with idiopathic GH deficiency (IGHD) (n = 6). The normal subjects had two peaks of plasma GHRH-LI after oral glucose administration. The initial peak GHRH-LI levels occurred 30-150 min after glucose ingestion and corresponded to an increase in blood glucose. The increment in plasma GHRH-LI levels 30 min after glucose ingestion [7.4 +/- 2.4 (+/- SEM) pg/ml] was significantly higher (P less than 0.05) than that during a control study. Second peaks in plasma GHRH-LI occurred 3.5-6 h after glucose ingestion, and the mean increment 5 h after glucose ingestion was 9.4 +/- 2.4 pg/ml. This second rise of plasma GHRH-LI coincided with a significant increase in plasma GH after reactive hypoglycemia. This second GHRH-LI peak and the rise of plasma GH after hypoglycemia were absent in patients with IGHD, whereas the first peak of plasma GHRH-LI appeared shortly after glucose ingestion in these patients as well as in normal subjects. In addition, hypoglycemia produced by iv injection of regular insulin (0.1 U/kg) was not accompanied by increases in plasma GHRH-LI and GH levels in patients with IGHD, whereas insulin-induced hypoglycemia resulted in significant elevations of both plasma GHRH-LI and GH levels in normal subjects. These findings suggest that peripheral plasma GHRH-LI is derived from the hypothalamus as well as from an extrahypothalamic source(s); extrahypothalamic GHRH is released shortly after glucose ingestion; and secretion of GHRH from the hypothalamus is stimulated by hypoglycemia.

Exercise capacity, energy metabolism, and beta-adrenoceptor blockade. Comparison between a beta 1-selective and a non-selective beta blocker.

The effects of beta 1 and beta 1/2 blockade on exercise capacity were studied in 9 healthy normotensive subjects. Progressive maximal bicycle ergometer tests, followed by an endurance test at 80% of maximal work load, were performed during randomized, double-blind 3 day treatment periods with placebo, atenolol (beta 1) and oxprenolol (beta 1/2). The reduction of maximal work capacity (ca. 10%) was similar with atenolol and oxprenolol, despite a more pronounced maximal heart rate reduction with atenolol (from 175 +/- 2 to 132 +/- 3 beats.min-1) than with oxprenolol (to 138 +/- 2 beats.min-1). Exercise time during the endurance test was reduced from 36 +/- 4 min with placebo to 27 +/- 3 min with atenolol (p less than 0.05) and 24 +/- 3 min with oxprenolol (p less than 0.01) (atenolol vs. oxprenolol: p less than 0.05). During the endurance test, plasma glycerol and non-esterified fatty acid concentrations were reduced with both atenolol and oxprenolol. The glycerol reduction was more pronounced with oxprenolol than with atenolol, plasma NEFA concentrations being similar. Plasma glucose and lactate concentrations were reduced by oxprenolol but not with atenolol. These data show that submaximal exercise capacity at work loads representing similar relative exercise intensities is reduced during non-selective and beta 1-selective beta blockade. This reduction may be related to the effects of beta 1 blockade on energy metabolism, with possibly an additional effect of beta 2 blockade.

Fetal heart rate responses to maternal exercise.

The fetal heart rate responses to mild, moderate, and strenuous maternal exercise were studied in 45 healthy subjects. In the majority of cases, the fetal heart rate increased during and after maternal exercise. Fetal bradycardia was recorded in five fetuses; this appears to be a sporadic event. There was no correlation between the individual fetal heart responses, gestational age, exercise intensity, and maternal circulating catecholamines.

Interactions of stress hormones on lipid and carbohydrate metabolism in man with partial insulin deficiency.

The metabolic responses to 4-h infusions of adrenaline (3 micrograms kg-1 h-1) and cortisol (10 mg m-2 h-1 for 2 h followed by 5 mg m-2 h-1 for 2 h), separately and in combination, have been studied in six healthy subjects with concurrent somatostatin infusion (250 micrograms h-1). A combined infusion of adrenaline, cortisol, glucagon (180 ng kg-1 h-1) and somatostatin has also been studied. Somatostatin plus adrenaline and somatostatin plus cortisol resulted in hyperglycaemia (at 240 min, somatostatin plus adrenaline 11.4 +/- 0.4 mmol l-1, P less than 0.001; somatostatin plus cortisol 6.7 +/- 0.3 mmol l-1, P less than 0.05; somatostatin alone 4.9 +/- 0.4 mmol l-1). No synergistic effect on blood glucose was seen with adrenaline and cortisol together. When glucagon was added, blood glucose rose more rapidly than without glucagon (9.3 +/- 0.4 mmol l-1 v. 7.2 +/- 0.5 mmol l-1 at 45 min, P less than 0.001), but plateau values were similar. Plasma NEFA levels were raised by somatostatin plus adrenaline (0.55 +/- 0.04-1.82 +/- 0.11 mmol l-1 at 60 min). Somatostatin plus cortisol had no more effect on plasma NEFA than somatostatin alone. During the combined infusion of somatostatin plus adrenaline plus cortisol, a synergistic effect on plasma NEFA was observed (2.30 +/- 0.11 mmol l-1 at 60 min, P less than 0.01 v. somatostatin plus adrenaline). This occurred despite a small escape of insulin secretion. The lipolytic actions of adrenaline are potentiated by elevated circulating cortisol levels in insulin-deficient man.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma vasoactive intestinal polypeptide, insulin, gastric inhibitory polypeptide, and blood glucose in late pregnancy and during and after delivery.

The plasma levels of the gastrointestinal regulatory peptides vasoactive intestinal polypeptide, insulin, and gastric inhibitory polypeptide, as well as blood glucose, were measured in six healthy women before, during, and after normal parturition at term. Plasma levels of vasoactive intestinal polypeptide increased significantly (p less than 0.05) during delivery and remained significantly elevated for 15 minutes post partum. Plasma insulin levels rose significantly (p less than 0.05) within 5 minutes after delivery and stayed three-fold and significantly elevated for 120 minutes post partum. Plasma levels of gastric inhibitory polypeptide decreased significantly (p less than 0.05) between 5 and 30 minutes after delivery. Blood glucose levels were significantly (p less than 0.05) increased during labor, delivery, and the early postpartum period compared to late pregnancy. These findings suggest a mediating role for vasoactive intestinal polypeptide, insulin, and gastric inhibitory polypeptide in the physiologic adaptations to normal pregnancy, delivery, and the postpartum period.

Effects of bombesin on fasting bile formation.

Adult dogs were previously prepared by cholecystectomy, ligation of the lesser pancreatic duct, and insertion of cannulae into the duodenum and stomach. After a 2-week period of postoperative recovery and an overnight fast, bile ducts were cannulated, gastric cannulae placed to open drainage and sodium taurocholate 500 mg hr-1 was administered to replace bile acids lost from the interrupted enterohepatic circuit. Bombesin was infused IV for 1 hour over the dose range, 0.625-10 ng kg-1 min-1. In control experiments 0.15 N NaCl was infused. Bombesin caused a significant increase in fasting bile flow, 3.0 +/- 0.2 ml/15 min to 4.2 +/- 0.3 ml/15 min (40%). Bile acid and phospholipid outputs were unchanged during bombesin. Bile cholesterol output decreased significantly during bombesin, 1029 +/- 142 micrograms/15 min to 856 +/- 109 micrograms/15 min (17%). The increase in bile flow was linearly related to the logarithm of the bombesin dose. In dogs with pyloric occlusion, to prevent acid from reaching the duodenum, bombesin increased bile flow and bicarbonate output but had no effect on 14C erythritol biliary clearance. Bombesin stimulated ductular bile acid independent bile formation in a dose-dependent manner. Bombesin also inhibited bile cholesterol output.

Actividad hipoglucemiante en ratas machos de derivados del ácido biciclo (3,1,0) hexano-6-carboxílico / Hypoglycemic activity in male rats of bicyclo (3,1,0) hexane-6-carboxylic acid derivatives

Se determinó la glucemia después de la administración subcutánea de glucosa a ratas machos adultas en varios tiempos. Se evaluó el efecto hipoglucemiante conocido del clorhidrato de feniletilbiguanida (FEB) después de su administración oral, y este compuesto sirvió como referencia. Se probaron seis nuevos compuestos sintetizados por los autores, relacionados con el ácido biciclo (3, 1, 0) hexano-6-hexo-carboxílico (ABCH). Se comprobó la actividad hipoglicemiante conocida del ABCH). Los seis nuevos compuestos conservaron la configuración exo y todos mostraron actividad hipoglucemiante oral en tiempos variables

The biochemical profile in Indian patients with non-insulin-dependent diabetes in the young with retinopathy.

A comparative study of the biochemical profile in 15 Indian patients with non-insulin-dependent diabetes in the young with retinopathy, and 15 matched patients without vascular disease, was undertaken. There were no significant differences between the lipid, lipoprotein and apoprotein levels between the 2 groups. While the fasting plasma glucose and glycosylated haemoglobin levels were significantly higher in the patients with retinopathy, there were no differences between the groups with regard to their insulin areas, glucose areas and insulinogenic indices. The retinopaths also had significantly lower serum magnesium levels than the patients without detectable retinal vascular disease.

A test strip method for visual and reflectometric reading of blood glucose.

A double field glucose oxidase test strip, B-M Haemoglucotest 1-44 R, was tested for stability of reaction and comparability of visual and reflectometric readings (evaluating four reflectometers) with a standard laboratory glucose oxidase analysis and showed excellent precision and accuracy within the whole range when estimated immediately. Readings after 1 and 7 days showed a systematic and increasing error with time, with spuriously high and low values in the lower (less than or equal to 4.0 mmol/l) and higher (greater than or equal to 8.1 mmol/l) part of the range, respectively. In the lower range, however, the error was in the order of 1 mmol/l only, thus stability of the reaction allows mailing the strips to the clinic for rechecking.

Congenital secondary hypothyroidism with low serum GH and prolactin levels in a 27-day-old male infant.

A male infant with secondary hypothyroidism is described. Within the first month after birth, the patient manifested feeding difficulties, lethargy, persistent jaundice, umbilical hernia, and large anterior and open posterior fontanels. The roentgenogram of the knee joints at 27 days showed absence of the distal femoral epiphyses. His serum thyroid-stimulating hormone (TSH) level was low despite decreased levels of triiodothyronine (T3) and tetraiodothyronine (T4) in serum. Assessment of the hypothalamic-pituitary hormone (TRH) nor growth hormone (GH) responses to L-arginine and insulin, while responses of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to luteinizing hormone-releasing hormone (LH-RH) and adrenocorticotropic hormone (ACTH) to insulin were within normal limits. The malady of the patient in this case was not detected by newborn screening for congenital hypothyroidism due to the fact that in the Aomori district of Japan thyroid screening involves only the measurement of TSH. Such measurement cannot detect cases of secondary or tertiary hypothyroidism such as our patient. Replacement therapy was initiated at 58 days and his physical and mental development has been regarded as normal since treatment.

Influence of insulin and glucagon on sodium balance in obese subjects during fasting and refeeding.

To delineate the hormonal mechanism of dietary-induced changes in sodium balance, the role of insulin and glucagon in natriuresis of fast was evaluated in obese subjects submitted to a total starvation and given either glucagon or somatostatin infusion on day 4 of fast. While large amounts of glucagon (1 mg over 6 h) stimulated concomitantly ketonaemia, ketonuria and renal sodium losses, the ten-times lower amounts of glucagon induced an increase in renal ketone body and sodium excretion without any significant change in ketonaemia. It was concluded, therefore, that elevated plasma glucagon level may enhance renal sodium loss in ketotic states, through a direct renal effect reducing tubular ketone body reabsorption, hence increased ketonuria and natriuresis. It appears nevertheless that decreased insulin secretion, rather than an increase in plasma glucagon level must be considered as a key hormonal factor responsible for natriuresis attending starvation. Indeed, the concomitant reduction in plasma glucagon and insulin levels, resulting from somatostatin infusion on day 4 of fast, was followed by significant increase in natriuresis. The latter observation supports several previous studies indicating that insulin stimulates sodium reabsorption by the kidney and that the reduction in insulin secretion may induce an increase in renal sodium excretion. It was concluded, therefore, that not only sodium intake but also the carbohydrate content of the diet should be reduced in an attempt to induce a negative sodium balance and to correct hypertension in obese subjects.

Effect of acute nonsurgical stress on fetal and maternal plasma glucose, glucagon and insulin concentration in sheep.

The purpose of this study was to investigate the effect of nonsurgical stress on plasma glucose, insulin and glucagon in the ewe and fetus. Plasma glucose, insulin and glucagon were measured before and after a 2 min period of verbal and physical startling of much greater magnitude than that to which we ewe is exposed during routine blood drawing. Studies were completed on 5 fed ewes, 5 fasted ewes and on 4 fetuses of fasted ewes. There were no significant differences after a startling compared to the control values. Thus, there appears no need to allow the ewe a prolonged period (more than 1-2 weeks) to become accustomed to handling by humans before chronic metabolic studies involving serum glucose, insulin and glucagon are undertaken.