In vivo studies on 5-hydroxytryptamine and insulin secretion in dogs and in man.
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Biomedical subjects
Publications and source records attributed to N Sicolo.
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The possibility that dietary-induced thermogenesis may be decreased in obesity has been proposed in recent years. However, the results of human studies so far obtained are conflicting. The present research was undertaken in order to clarify this question. We studied postprandial thermogenesis induced by ingestion of a mixed meal and of a carbohydrate mixture in 15 normal and 12 obese subjects. Blood glucose and plasma insulin levels were measured at the same time. The data obtained have shown that the mean resting metabolic rate (RMR) expressed as a function of body weight3/4, is almost the same in obese as in normal-weight subjects (0.115 +/- 0.018 vs 0.133 +/- 0.021 kj/min/kg3/4, respectively). Moreover, the increment of mixed-meal induced thermogenesis (MM-IT) was 48 +/- 22% in normal and -0.8 +/- 12% in obese subjects, respectively (p less than 0.01). Carbohydrate induced thermogenesis (CHO-IT) appeared slightly higher in normal-weight than in obese subjects (159 +/- 66 vs 98 +/- 46). After carbohydrate ingestion we observed a higher glycemic and insulinemic response in obesity. These results indicate that thermogenesis induced by ingestion of food is reduced in obese subjects; they are also compatible with the idea that insulin resistance could play a role in this phenomenon.
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In order to study endocrine and metabolic responses to normal food ingestion, 8 'healthy' subjects received a standard mixed meal which reflected the composition of Western diet (CHO 47%, protein 23%, fat 26%, alcohol 4%), in 20 min. Before and after the meal, in each subject glucose, lactate, FFA, insulin, C-peptide, glucagon and HGH were determined. The results showed that glycemic and insulinemic responses were not very different from those observed after the classical oral glucose tolerance test. Plasma FFA and blood lactate decreased progressively after the meal. Plasma glucagon and HGH showed opposite changes: pancreatic glucagon rose and HGH slightly declined after composite food ingestion.
In order to determine the endocrine and metabolic state of thyrotoxicosis we measured blood glucose and plasma insulin response to ingestion of a mixed meal in 19 euthyroid and 9 hyperthyroid subjects. Moreover concentrations of glucose, free fatty acids (FFA), glycerol, acetoacetate (AcAc) beta-hydroxybutyrate (beta-OHB), insulin and human growth hormone (hGH) were determined in the blood of both healthy and hyperthyroid patients after an overnight and a 39-h fast. In another group of thyrotoxics the overnight fasting respiratory quotient (RQ) was measured. After a mixed meal blood glucose and plasma insulin changes of FFA, AcAc and beta-OHB was significantly higher in thyrotoxics, whereas hGH increase did not appear significantly greater in these subjects. There was no statistical difference between the respiratory quotient mean values found in hyperthyroid and in control subjects. In conclusion, these data indicate that in thyrotoxicosis absolute insulin response to a mixed meal is normal and that food deprivation considerably increase lipid mobilization from adipose tissue and causes an exaggerated starvation ketosis. The RQ mean valoue suggests that in the hyperthyroid state lipid-derived fuel as well as carbohydrate-derived fuel contributes to the increased oxygen consumption.
Although it is well known that growth hormone may influence protein metabolism, few investigations have been undertaken on serum protein levels in acromegaly; recently hypoglobulinemia has been observed in this endocrine disorder. In 28 acromegalic patients and 56 control subjects sera have been analyzed for total protein determination and for electrophoretic protein separation. The results have shown that in acromegalic there is a slight but statistically highly significant decrease of serum total protein (mean +/- SE 6.66 +/- 0.07 g/100 ml vs 7.10 +/- 0.07 g/100 ml), albumin, alpha 1 and alpha 2-globulins. Since growth hormone stimulates protein synthesis, the pathophysiological significance of hypoproteinemia of acromegaly is at present obscure.
To study the opioid control on LH and FSH secretion in Klinefelter subjects (KS), the response of gonadotropin to an opioid antagonist, naloxone, was examined in 8 KS (age range 25-35 yrs) and in 8 age matched normal men. In 6 KS with low testosterone plasma levels, naloxone infusion were also performed after treatment with testosterone enanthate, 200 mg i.m. every 3 weeks for 4 months. FSH did not show any important variation in KS and in normal men during naloxone infusion. In KS the percentage of naloxone induced LH increase was significantly lower than in controls and there was no correlation between testosterone plasma levels and LH increase after naloxone infusion. LH increases after naloxone infusion were not significantly different before and after testosterone treatment. The increases of naloxone induced LH plasma levels, before and after testosterone treatment, correlated well between themselves (r = 0.93-p less than 0.01). Plasma levels decreased in all patients after testosterone treatment, but only in two was there a return to normal range. There is a clearly positive linear correlation between the percentage of LH decrease after testosterone treatment and LH increase after naloxone infusion (r = 0.81; p less than 0.01). After testosterone therapy FSH plasma levels fall by 63 +/- 15% in all patients and did not show any important variation after naloxone infusion. In conclusion, our data are in agreement with the hypothesis that in Klinefelter's syndrome an alteration of opioid control on gonadotropin secretion may exist. This alteration does not appear to be due to androgen deficiency, but rather it may be caused by genetic abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
Anomalies in prostaglandin (PG) synthesis have been suggested in both experimental and human diabetes mellitus; increased levels of plasma and tissue eicosanoids has been recently reported by several investigators. One step in prostaglandin synthesis is the enzymatic hydrolysis of membrane phospholipids by Phospholipase A2 (PLA2). Nevertheless the alternative pathway involving Phospholipase C must be considered. An evaluation of PLA2 activity is therefore a useful method for studying prostaglandin synthesis in the peripheral target tissues of insulin activity. We studied PLA2 activity in normal and diabetic rat muscle. Streptozotocin-induced diabetic rats showed significantly higher muscular PLA2 activity when compared with controls (3.04 x 10(-2) +/- 0.50 x 10(-2) versus 1.34 x 10(-2) +/- 0.35 x 10(-2) arachidonic acid pMol.mg protein-1.min-1 (p less than 0.01). This effect was not observed in diabetic animals successfully treated with insulin (1.78 x 10(-2) +/- 0.5 x 10(-2) versus 1.34 x 10(-2) +/- 0.35 x 10(-2) arachidonic acid pMol.mg protein-1.min-1), and a significant correlation was found between blood glucose and muscular PLA2 activity (r = 0.42; p less than 0.05). Our results clearly show that in streptozotocin-induced diabetic rats muscular PLA2 activity is significantly higher. The relationship between blood glucose levels and muscular PLA2 activity and the decrease of PLA2 activity after insulin treatment suggest that these changes may be related to a defect in insulin effect.
In order to check whether reduced postprandial thermogenesis, as found in obese subjects depends on insulin resistance, the study tested whether the thermogenetic response to glucose in a group of obese subjects and a group of normal weight subjects differed from that obtained using an insulin-independent monosaccharide such as fructose. Nine obese subjects and 6 control subjects were included in the study. An oral glucose tolerance and fructose tolerance test (75 g) was performed in all subjects on different days. Energy expenditure was calculated both in basal conditions and during the test (resting metabolic rate: RMR) using indirect calorimetry expressed per kg of lean weight, as assessed using bioimpedance measurement techniques. Blood samples were collected to assay glycemia and insulinemia. Results show that increased RMR induced by glucose was significantly reduced in the group of obese subjects compared to controls. In the same group of obese subjects, RMR was found to be significantly higher following fructose in comparison to the glucose response but did not differ from that in controls. Data confirm the existence of reduced thermogenesis in obese subjects induced by glucose. The fact that this phenomenon was not recorded in the same subjects following the fructose tolerance test, whose metabolism is insulin-independent, supports the hypothesis that reduced glucose-induced thermogenesis in obese subjects may depend on insulin resistance.
Somatostatin analogue (Sandostatin; SMS 201-995) is utilized as a therapy in acromegaly because of its efficiency in inhibiting GH secretion; it induces some clinical improvements, such as headache remission in acromegalic patient, which seem to be unrelated to Gh normalization. We have examined 8 acromegalic patients, suffering from headache, after injection of saline solution and subsequently of SMS 201-995 (100 y), in order to study the mechanism of analgesic effect induced by Sandostatin administration. Headache, by autovaluation test, heart rate frequency, PAO, sistolic and diastolic blood velocity in medial cerebral artery, by utilizing Transcranial Doppler Sonography (SDSV), have been measured before and after saline and after SMS 201-995. GH and beta-endorphin have been also assayed in plasma samples. All patients have shown a rapid and complete improvement in headache after Sandostatin administration. At the same time we have observed an increase in SDSV and a parallel slight increase in PAO values, more evident in the diastolic phase. Plasma beta-endorphin assay has shown rather conflicting results after SMS 201-995 administration. Our results confirm an important and rapid analgesis effect of Sandostatin on acromegaly headache unrelated to GH normalization. The cerebral emodinamic changes suggest their involvement in Sandostatin induced analgesia.