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Biomedical subjects

R Vettor

Publications and source records attributed to R Vettor.

At least 73 records · Page 4Linked to original sources

Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity.

Chronic intracerebroventricular (icv) administration of neuropeptide-Y (NPY; 10 micrograms/day) was performed in normal female rats to investigate its hormonal and metabolic consequences. Intracerebroventricular NPY produced hyperphagia, increased basal insulinemia, as well as liver and adipose tissue lipogenic activity. It also increased basal morning corticosteronemia. When NPY-induced hyperphagia was prevented by pair-feeding, the icv NPY treatment resulted in the same increases in basal insulinemia and corticosteronemia, and liver and white adipose tissue lipogenesis was still higher than that in respective controls. Under the ad libitum and pair-feeding conditions, icv NPY stimulated glucose uptake as well as total lipoprotein lipase activity in white adipose tissue; it resulted in an increase total activity of hepatic and white adipose tissue acetyl coenzyme-A-carboxylase. As all hormonal and metabolic changes elicited by icv NPY remained present (at the same or to a lesser extent depending upon the parameter considered) when hyperphagia was prevented by pair-feeding, it was, thus, shown that icv NPY per se induces peripheral hormonal and metabolic alterations via efferent routes, which remain to be determined. The effects of icv NPY reported in this study are similar to the defects observed in the early phase of genetic obesity in rodents, the hypothalamus of which has increased NPY levels. NPY could, thus, be of relevance in the occurrence of genetically induced obesity.

Adipose Tissue↗

Endocrine pancreatic function in pheochromocytoma.

In six patients with pheochromocytoma oral glucose tolerance test (OGTT) and arginine test were carried out. Blood insulin and glucagon response were investigated. In subjects with adrenal tumor glycemic curve pattern was typical: a rapid and exaggerated increase of glycemia followed by an abrupt drop. Absolute insulinemic response to oral glucose was normal, but inappropriate to glycemic stimulus. Arginine infusion provoked a slightly above normal increase in blood glucose and a normal increase in blood glucagon. In three of the patients studied postoperatively, reduced glycemic response to glucose was observed, whereas there were no evident variations in blood insulin and glucagon response. These data suggest that in pheochromocytoma impaired glucose tolerance is partly due to the reduced insulin response to oral glucose load.

Adrenal Gland Neoplasms↗

Possible involvement of endogenous opioids in beta-cell hyperresponsiveness in human obesity.

Since increased opiate production in obesity has been reported, the effects of naloxone in obese subjects were studied in order to ascertain whether endogenous opioid peptides play a role in the abundant insulin secretion of obesity. The results obtained showed that intravenous administration of naloxone considerably reduced insulin of obese subjects to a mixed meal, whereas it did not modify the blood insulin response to arginine or glucose infusion. Glucagon secretion to ingestion of a mixed meal and to arginine infusion was not modified by the opioid receptor blocking agent. This study seems to indicate that hyperproduction of endogenous opioid peptides in obesity increases insulin secretion stimulated by food intake, whereas it does not appreciably affect insulin production stimulated by circulating glucose or aminoacids.

Adolescent↗

Association of BK virus with human brain tumors and tumors of pancreatic islets.

BK virus (BKV) DNA was detected by Southern blot hybridization in 19 out of 74 (25.6%) human brain tumors and in 4 out of 9 (44.4%) human tumors of pancreatic islets. BKV DNA was free, in an episomal state and generally in a low copy number (0.2 to 2 genome equivalents per cell). Only occasional tumors contained 10 to 20 genome copies per cell. Viral DNA sequences integrated into cellular DNA were not detected. A number of tumors expressed BKV-specific RNA and T antigen. By transfection of total tumor DNA into human embryonic fibroblasts, viruses with the biological and antigenic properties of BKV were rescued from 6 brain tumors and from 2 tumors of pancreatic islets. Restriction endonuclease mapping of the genomes of the rescued viruses showed that they differ from wild-type BKV. They are all similar to each other and to BKV-IR, a virus previously rescued from a human tumor of pancreatic islets, suggesting the possible association of a BKV variant with specific types of human neoplasms. The significance of the relationship of these BKV variants to human tumors and their possible etiologic role in human oncogenesis are discussed.

Adenoma, Islet Cell↗

Effect of prolonged physical exercise on muscular phospholipase A2 activity in rats.

Prolonged muscular exercise stimulates glucose uptake by the working muscles themselves. The mechanism of this phenomenon is at present unclear. It has been proposed that the kallikrein-kinin-prostaglandin system plays a role in the physiological regulation of muscular glucose metabolism during exercise. Since bradykinin can stimulate phospholipase A2, a key enzymatic step in prostaglandin synthesis, phospholipase A2 activity was assayed in rats at rest and in rats compelled to swim for 60 minutes. The physiological significance of an increase in muscular phospholipase A2 activity is not clear. Since bradykinin can stimulate both muscular glucose uptake and phospholipase A2 activity, it is possible that the increased activity of this enzyme is involved in the exercise-induced increase of muscular glucose uptake. Phospholipase A2 activity was strongly increased in the exercising rat muscles. A small but significant increase in phospholipase A2 activity was observed in the heart, whereas no variation in activity was demonstrated in either the kidney or the liver of exercising rats. These findings strongly indicate that prolonged exercise increases muscular phospholipase A2 activity only in the muscle and heart. This phenomenon appears to be strongly related to muscular contraction, since other stress situations such as cold exposure did not modify phospholipase A2 activity. Our data are in agreement with the hypothesis of a possible involvement of prostaglandins in the priming action of insulin on glucose uptake during muscular work.

Animals↗

Effect of exercise on plasma kallikrein and muscular phospholipase A2 activity in rats.

Many experimental observations show that prolonged physical exercise produces an increase of muscular glucose uptake. Recent findings suggest that the kallikrein-kinin-prostaglandin system may be related to this phenomenon, but so far, no direct evidence of quantitative alteration in this system has been observed during exercise. We measured plasma kallikrein and muscular phospholipase A2 activity, respectively the first and the last steps of reactions leading to prostaglandin synthesis. We demonstrated, for the first time, that during exercise plasma kallikrein activity increases in rats. We also observed an increase of muscular phospholipase A2 activity after exercise and a positive correlation between these parameters. Our findings demonstrate, under physiological conditions of enhanced muscular glucose uptake, a concomitant significant increase of plasma kallikrein and muscular phospholipase A2 activity, supporting the hypothesis that activation of the kallikrein-kinin-prostaglandin system may play some part in the enhanced muscular glucose uptake during physical activity.

Animals↗

Antithrombin III activity and concentration in diabetes mellitus.

Antithrombin III (AT III) levels have been reported to be low, normal, and high in diabetes mellitus. Furthermore, a discrepancy between AT III activity and antigen concentration was reported. We have evaluated the behaviour of AT III activity and antigen level both in type 1 and type 2 diabetes, either in uncontrolled or in well controlled patients. AT III activity and antigen levels showed values similar to normal. No difference was seen between type 1 and type 2 diabetes. Similar results were observed in the group of well controlled diabetic patients. AT III activity and antigen did not correlate with blood glucose and glycosylated haemoglobin (HbA1). No difference was observed between AT III activity and antigen levels in any group. Therefore the hypercoagulable state found in diabetes mellitus does not depend on AT III modifications. A discrepancy between AT III activity and antigen was not confirmed. A dysantithrombinaemia, explained on the basis of an inactivation of protein glycosylation in diabetes mellitus has not been confirmed.

Adult↗

Role of antecedent mumps and reovirus infections on the development of type 1 (insulin-dependent) diabetes.

Type 1 diabetes mellitus is thought to derive from organ-specific autoimmune reactions, probably triggered by environmental factors. In view of the possible involvement of mumps virus and reoviruses in the pathogenesis of autoimmune endocrine disease, serum antibody levels to these viruses were measured in newly-diagnosed diabetic patients aged 5 to 25 years and in matched control subjects. Diabetic patients showed a significantly lower prevalence and reduced titers of antibodies to mumps and reoviruses. By contrast, the antibody response to measles virus (a non-diabetogenic agent) was remarkably similar in the two groups. It is suggested that individuals with an impaired humoral response to some viral agents are at increased risk of developing diabetes when exposed to pancreotropic viruses.

Adolescent↗

Plasma kallikrein activity in human diabetes mellitus.

It has recently been observed that administration of bradykinin to diabetic patients improves peripheral glucose utilization. To verify whether there is an alteration of the kallikrein-kinin system in human diabetes, plasma kallikrein activity was measured in 47 diabetic patients and in 20 control subjects. In diabetics plasma kallikrein activity was significantly higher than in controls: 1.04 +/- 0.04 U/ml (p less than 0.001). Although they do not refute the hypothesis that there is an alteration of the kallikrein-kinin system in diabetes mellitus, these findings do not support such a hypothesis either. Increased synthesis of plasma kallikrein activity may be due to increased synthesis of carbohydrate-protein compounds in diabetes mellitus.

Adult↗

Contact phase of blood coagulation in diabetes mellitus.

The first phase of the intrinsic coagulation system was studied in twenty-six diabetic outpatients. The parameters tested were kallicrein, prekallicrein, factor XI and factor XII activities. Kallicrein and factor XI showed significantly elevated activities as compared with a normal control group (P less than 0.05 and less than 0.001, respectively). Factor XI and factor XII levels were higher in non-insulin dependent than in insulin dependent diabetics. We found that the kallicrein-prekallicrein system was activated in our diabetic patients and that such activation could probably be secondary to lesions of the vascular endothelium present in long-term diabetics. No correlation was found between glycaemia and activity levels of this system. Our data represent another demonstration of the existence of a hypercoagulable state in diabetes mellitus.

Adult↗

Plasma and urine free L-carnitine in human diabetes mellitus.

L-carnitine is essential for the transport of long-chain fatty acids into mitochondria and their oxidation. Recently, a relationship between plasma free fatty acids (FFA) and L-carnitine metabolism has been observed. Plasma free L-carnitine (FC), FFA, triglycerides, cholesterol, blood glucose concentration and daily excretion of FC were determined in 20 diabetic patients as well as in 18 control subjects. Both in male diabetics and in male controls, plasma FC was significantly higher than in females. Mean plasma FC was found to be significantly reduced in diabetics (21 +/- 2 vs 35 +/- 2 mumol/1 in non-diabetic subjects; p less than 0.005). Daily urinary excretion of FC was clearly lower in diabetic patients than in controls (172 +/- 34 vs 403 +/- 38 mumol/24 h; p less than 0.001). The reduced plasma FC in diabetes mellitus may be due to redistribution between circulating free and esterified carnitine and to increased utilization of FC for synthesis of acylcarnitine in tissues.

Blood Glucose↗

Lack of effect of calcium infusion on blood glucose and plasma insulin levels in patients with insulinoma.

In vitro calcium plays a fundamental role in regulating insulin secretion. On the other hand, the influence of calcium excess on insulin release in vivo is not clearly defined. Recently, calcium infusion has been proposed as a provocative test for the diagnosis of insulin-secreting tumors. A 2-h infusion of calcium gluconate was performed (4 mg/kg . h) in six patients with islet cell adenoma. As a result, mean calcium plasma levels increased from 9.6 +/- 0.4 to 11.6 +/- 0.8 mg/100 ml. During calcium infusion, blood glucose and plasma insulin concentrations remained unchanged. These observations suggest that calcium fails to stimulate basal insulin secretion even in cases of organic hyperinsulinism. They show that calcium infusion is not helpful as a provocative test in the diagnosis of insulinoma.

Adenoma, Islet Cell↗

Dietary-induced thermogenesis in obesity. Response to mixed and carbohydrate meals.

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.

Adult↗

Hypoproteinemia in acromegaly.

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.

Acromegaly↗