Biomedical subjects

R Vettor

Publications and source records attributed to R Vettor.

At least 55 records · Page 3Linked to original sources

PubMed1998

Serum leptin in obese women with polycystic ovary syndrome is correlated with body weight and fat distribution but not with androgen and insulin levels.

Leptin is a hormone produced in the adipose tissue and its concentrations in peripheral blood are significantly correlated with the amount of body fat. Whether other factors, including the pattern of body fat distribution and several hormones (such as insulin, sex steroids, and glucocorticoids), may be involved in the regulation of circulating blood leptin levels is controversial. Women with the polycystic ovary syndrome (PCOS) are hyperandrogenic and most of them are characterized by hyperinsulinemia, insulin resistance, and obesity, particularly the visceral phenotype. To assess the potential contribution of anthropometric factors, androgens, and insulin in determining leptin levels, we examined their relationship with body-mass index (BMI), visceral (VAT) and subcutaneous (SAT) adipose tissue areas, basal androgen levels, and fasting and glucose-stimulated (AUC) insulin in different groups of obese women with PCOS (n = 23) and of age-matched obese (n = 16) and non-obese (n = 10) otherwise healthy controls. The VAT/SAT ratio was measured as a parameter of body fat distribution. Serum leptin levels were significantly higher in obese PCOS women than in obese and normal-weight healthy controls and, within the controls, in the obese than in the non-obese group. In all women considered together, and in each group separately, leptin concentrations were highly significantly correlated with BMI. In addition, after adjusting for BMI, both VAT and the VAT/SAT ratio were positively and significantly correlated with leptin. Partial correlations with the VAT/SAT ratio remained significant in both the obese PCOS group and in controls considered separately, whereas the correlation with the SAT value was significant only in the control group. After adjusting for BMI, no correlation between leptin, androgens and fasting or stimulated (like AUC) insulin was found. These findings indicate that leptin levels in obese women with PCOS are higher than those observed in obese and non-obese controls. Moreover, they suggest that, other than BMI, the pattern of body fat distribution may be an independent factor related to circulating leptin levels, which, on the contrary, do not appear to be related to either androgen or insulin concentrations.

Adipose Tissue↗

PubMed1998

Corticosteroid receptors in mononuclear leucocytes of obese subjects.

Abnormalities of the hypothalamus-pituitary-adrenal axis and hypersensitivity to corticosteroids have been suggested as major determinants of the development of visceral obesity. Since at the cellular level most effects of corticosteroids are mediated by specific receptors, we evaluated the number of type I and type II corticosteroid receptors in mononuclear leucocytes of 26 obese and 13 control subjects. We also studied the relationship between corticosteroid receptors, measured by radioreceptor assay, and abdominal visceral fat, evaluated by computed tomography scan, plasma and urine corticosteroid hormone concentrations and overall glucose metabolism, assessed by euglycaemic-hyperinsulinaemic clamp. We observed a decrease in type II receptors in the obese subjects (1746 +/- 160 vs 2829 +/- 201 per cell; P < 0.0001), with no change in type I receptors. Type II receptors decreased in relation to body mass index (r = -0.53; P < 0.005) and total glucose disposal (r = 0.51; P < 0.01). Abdominal visceral fat did not correlate with type II receptor number, but did correlate with total glucose disposal (r = -0.35; P < 0.05); the rate of glucose disposal was lower in obese subjects (3.3 +/- 0.3 vs 7.4 +/- 0.4 mg/kg per min; P < 0.001). Plasma and urine cortisol did not differ between the two groups. However, a direct correlation between type II receptor number and both plasma (r = 0.43; P < 0.02) and urine cortisol concentrations (r = 0.60; P < 0.05) was observed. In conclusion, the number of type II corticosteroid receptors in mononuclear leucocytes was found to be lower in obese subjects. This abnormality appears to be related to the degree of adiposity and to the main endocrine-metabolic features of the obesity syndrome, further supporting the hypothesis of involvement of hypothalamus-pituitary-adrenal axis hyperactivity in the pathophysiology of obesity.

Adult↗

PubMed1997

Impaired counterregulatory hormonal and metabolic response to exhaustive exercise in obese subjects.

A reduction of postprandial thermogenesis has been described in obesity; insulin resistance and/or decreased sympathetic nervous system activity seem to play the major role in its pathogenesis. On the other hand, a normal energy expenditure during exercise has been reported. At present, the response and the role of catecholamines in energy metabolism during exercise in obesity have not been well clarified yet. The aim of this work was to study the metabolic and hormonal changes caused by intense exercise in obesity. Nine obese subjects and ten normal weight controls were submitted to exhaustive exercise on a cycloergometer. Blood glucose, free fatty acids (FFA), glycerol, lactate, beta-OH-butyrate, insulin, glucagon, plasma growth hormone (HGH), catecholamine plasma levels were assayed before and at the end of exercise, and after a recovery period. The energy cost of exercise was evaluated by indirect calorimetry. In our experiment muscular exercise did not provoke any change in blood glucose and FFA plasma levels in either of our groups. In the obese subjects the insulin plasma levels were higher than in the controls. Glucagon plasma levels did not change. The exercise responses of norepinephrine (NE) (4.28 +/- 0.74 vs 8.81 +/- 1.35 nmol/l; P < 0.01), epinephrine (E) (234.21 +/- 64.18 vs 560.51 +/- 83.38 pmol/l; P < 0.01) and plasma growth hormone (HGH) (134.84 +/- 58.97 vs 825.92 +/- 195.25 pmol/l; P < 0.01) were significantly lower in obese subjects. At the end of exercise, the thermic effect of exercise did not differ between obese and control subjects (0.335 +/- 0.038 vs 0.425 +/- 0.040 kJ/min x kg fat-free mass. Our findings indicate that an impaired counterregulatory hormone response to exercise exists in obese subjects. The thermic effect of exercise does not seem to be affected by either the reduced catecholamine response nor insulin resistance.

Adult↗

PubMed1997

Lactate infusion in anesthetized rats produces insulin resistance in heart and skeletal muscles.

Plasma lactate is elevated in many physiological and pathological conditions, such as physical exercise, obesity, and diabetes, in which a reduction of insulin sensitivity is also present. Furthermore, an increased production of lactate from muscle and adipose tissue together with increased gluconeogenic substrate flux to the liver plays a primary role in enhancing hepatic glucose production (HGP) in diabetes. It has been shown that lactate may interfere with the utilization and oxidation of other substrates such as free fatty acids (FFAs). The aim of this study was to investigate if lactate infusion affects peripheral glucose utilization in rats. Animals were acutely infused with lactate to achieve a final lactate concentration of 4 mmol/L. They were then submitted to a euglycemic-hyperinsulinemic clamp to study HGP and overall glucose metabolism (rate of disappearance [Rd]). At the end of the clamp, a bolus of 2-deoxy-[1-3H]-glucose was injected to study insulin-dependent glucose uptake in different tissues. The results show that lactate infusion did not affect HGP either in the basal state or at the end of clamp, whereas glucose utilization significantly decreased in lactate-infused rats (26.6 +/- 1.1 v 19.5 +/- 1.4 mg.kg-1.min-1, P < .01). A reduction in the tissue glucose utilization index was noted in heart (18.01 +/- 4.44 v 46.21 +/- 6.51 ng.mg-1.min-1, P < .01), diaphragm (5.56 +/- 0.74 v 9.01 +/- 0.93 ng.mg-1.min-1, P < .01), soleus (13.62 +/- 2.29 v 34.05 +/- 6.08 ng.mg-1.min-1, P < .01), and red quadricep (4.43 +/- 0.73 v 5.88 +/- 0.32 ng.mg-1.min-1, P < .05) muscle in lactate-infused animals, whereas no alterations were observed in other muscles or in adipose tissue. Therefore, we suggest that acute lactate infusion induces insulin resistance in the heart and some muscles, thus supporting a role for lactate in the regulation of peripheral glucose metabolism.

Adipose Tissue↗

PubMed1997

Effects of acute hyperinsulinemia on testosterone serum concentrations in adult obese and normal-weight men.

In a previous study performed in adult obese and normal-weight male subjects, we found that suppression of insulin levels by diazoxide reduced testosterone and increased sex hormone-binding globulin (SHBG) blood concentrations. These and other data suggested that insulin may have a regulatory capacity in testosterone secretion and/or metabolism in men, similar to what has already been demonstrated in women. In this study, we investigated the effects of acute hyperinsulinemia on major androgen levels, including testosterone, in two groups of normal-weight in = 11) and obese (n = 9) men. Acute hyperinsulinemia was obtained by the euglycemic-hyperinsulinemic clamp technique. Relationships between the degree of insulin resistance (ie, total glucose disposal [M value]) and testosterone levels were also evaluated. Basal testosterone levels in obese subjects (10.40 +/- 3.02 nmol/L) were significantly lower than in normal-weight controls (15.50 +/- 4.65 nmol/L, P < .01), whereas no difference was present in androstenedione and dehydroepiandrosterone sulfate (DHEA-S) concentrations. During the clamp study, testosterone was significantly increased in the obese group (11.79 +/- 3.64 nmol/L, P < .05) but not in the control group (15.81 +/- 4.54 nmol/L, P = NS). The other two androgens did not significantly change in either the obese or control group. There was a highly significant correlation between baseline testosterone concentrations, with M values suggesting a relationship between impaired peripheral insulin sensitivity and reduced plasma testosterone concentrations. It should be pointed out that there was a certain discrepancy in the testosterone variations, particularly in the control group, in which two thirds of the subjects had no change or some decrease in testosterone levels, whereas in the remainder testosterone increased over the values of the assay variation coefficient. These findings are consistent with the hypothesis that insulin may regulate testosterone blood levels also in male subjects. Whether these effects are primarily due to increased hormone secretion or reduced clearance needs to be investigated.

Acute Disease↗

PubMed1997

Visceral adipose tissue impairs insulin secretion and insulin sensitivity but not energy expenditure in obesity.

In obesity, a central pattern of fat distribution is mostly associated with hyperinsulinemia, insulin resistance, and hyperlipemia, thus promoting the development of non-insulin-dependent diabetes mellitus and cardiovascular disease. In addition, in obesity, changes in energy expenditure are hypothesized to be involved in the development or maintenance of excessive body fat storage. In this study, abdominal fat distribution by computed tomographic (CT) scan was used to study the relation between the visceral fat depot, insulin secretion, and insulin sensitivity in a group of obese subjects with normal glucose tolerance (n = 26; body mass index [BMI], 39 +/- 1 kg/m2) and a group of normal-weight control subjects (n = 9; BMI, 23 +/- 1 kg/m2). The minimal model method was used to assess insulin sensitivity, S(I), and first-phase (phi1) and second-phase (phi2) beta-cell sensitivity from plasma glucose, insulin, and C-peptide concentrations measured during an intravenous glucose tolerance test ([IVGTT] 0.33 g/kg body weight). Moreover, we evaluated the relationships between these parameters and the resting metabolic rate (RMR) and glucose-induced thermogenesis (GIT) measured by indirect calorimetry. The data show the following: (1) in obese subjects, phi1 is greater but not statistically different from the value in control subjects (252 +/- 41 v 157 +/- 25 dimensionless 10(9)); (2) phi2 is significantly higher in obese subjects (27 +/- 4 v 14 +/- 2 min(-1) x 10(9), P < .05), with a positive correlation between the amount of visceral adipose tissue (VAT) and phi2 (r = .49, P < .05); (3) S(I) is decreased in the obese group (2.8 +/- 0.3 v 9.7 +/- 1.6 10(-4) x min(-1)/microU x mL(-1)), P < .0001), with a negative correlation of S(I) with the adiposity index BMI (r = -.67, P < .0001) and VAT (r = .56, P < .05); (4) RMR, expressed in absolute terms, was significantly increased in obese versus lean subjects (5.9 +/- 0.2 v 4.6 +/- 0.3 kJ/min, P < .01), whereas when RMR was adjusted for fat-free mass (FFM), the difference between the two groups disappeared (0.09 +/- 0.003 v 0.09 +/- 0.002 kJ/min x kg FFM). We did not observe any difference in GIT between lean and obese subjects. Moreover, GIT was significantly correlated with FFM (r = .69, P < .005), but not with BMI. The amount of VAT did not correlate with RMR or GIT. In conclusion, these results suggest that in obese subjects with normal glucose tolerance, insulin sensitivity is impaired and the beta-cell hyperresponse to glucose is mainly due to an enhanced second-phase beta-cell secretion. The degree of visceral fat deposition seems to affect insulin secretion and worsens insulin sensitivity, but does not influence energy expenditure.

Abdomen↗

PubMed1997

Insulin induces rapid changes of plasma leptin in lean but not in genetically obese (fa/fa) rats.

OBJECTIVES: To evaluate the plasma leptin concentration in lean and genetically obese fa/fa rats and to assess the response to 2 h hyperinsulinaemia. BACKGROUND: The recently discovered peptide leptin is a putative link between the size of the adipose mass and the hypothalamic centres controlling feeding behaviour. Several genetic models of animal obesity have been characterized as carriers of mutations of either the ob gene or leptin receptor. EXPERIMENTAL DESIGN: Lean (+/?) and obese (fa/fa) Zucker rats were studied under pentobarbital anaesthesia and underwent a 2 h euglycaemic hyperinsulinaemic clamp. Plasma leptin was measured in basal condition and at the end of the clamp study. Glucose rate of disappearance was evaluated by means of the isotope dilution technique using 3-3H-glucose as tracer. RESULTS: fa/fa rats showed a 40 fold higher leptin concentration compared to lean littermates (0.47 +/- 0.10 vs 19.55 +/- 1.50 ng/ml, P < 0.0001). Euglycaemic hyperinsulinaemia increased plasma leptin in lean but not in genetically obese rats. CONCLUSIONS: Our results suggest that insulin may be a regulator of in vivo leptin secretion by adipose tissue of lean rates whereas it is ineffective in increasing plasma leptin in obese Zucker rats.

Animals↗

PubMed1997

Leptin and the hypothalamic-pituitary-adrenal axis activity in women with different obesity phenotypes.

OBJECTIVE: Women with visceral obesity may have hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Since glucocorticoids are involved in the expression of the ob gene, this study was carried out to investigate the relationship between serum leptin and the activity of the HPA axis in women with different obesity phenotypes. DESIGN: Cross sectional clinical study. SUBJECTS: Fifteen obese (Body Mass Index BM128 kg/m2) women and ten normal weight control women (BM126 kg/m2) were included in the study. MEASUREMENTS: Body fat distribution was defined by CT scan at the L4-L5 level. Baseline blood samples were obtained for hormone concentrations. The activity of the HPA axis was evaluated by measuring ACTH and cortisol blood levels after combined iv administration of corticotropin releasing factor (100 microg) + arginine-vasopressin (0.3 IU). RESULTS: Baseline cortisol, ACTH, and androgen levels were similar in all groups, whereas leptin levels were significantly higher in the obese groups than in normal weight controls, without any significant difference between women with different obesity phenotypes. Incremental areas of ACTH and cortisol were significantly higher in women with visceral obesity than in those with subcutaneous obesity and controls. No significant correlation was found between the activity of the HPA axis and leptin concentrations. Leptin showed a highly significant correlation with BMI and subcutaneous fat and a weak but significant correlation with visceral fat and the visceral-to-subcutaneous fat ratio. CONCLUSION: Women with different obesity phenotypes had similar serum leptin concentrations but different HPA axis activity, and there was no correlation between them.

Adrenocorticotropic Hormone↗

PubMed1997

Gender differences in serum leptin in obese people: relationships with testosterone, body fat distribution and insulin sensitivity.

Testosterone levels are decreased in obese men but increased in obese women. The interplay between gonadal steroids and leptin is, at present, far from being elucidated. This study was carried out to investigate the relationship between serum leptin, plasma insulin, insulin sensitivity and free testosterone in 46 men (29 obese and 17 lean) and 65 premenopausal women (42 obese and 23 lean). In all subjects, anthropometric parameters and serum levels of insulin, leptin, free testosterone (T), dehydroepiandrosterone sulphate and sex hormone-binding globulin were measured. An oral glucose tolerance test (OGTT) and an insulin tolerance test were also performed to determine the insulin sensitivity index. Our results show a significant difference in serum leptin between lean and obese men (3.19 +/- 0.71 vs. 20.28 +/- 0.26 ng mL-1; P < 0.0005) as well as between lean and obese women (10.78 +/- 2.14 vs. 34.79 +/- 2.26 ng mL-1; P < 0.00001). Basal T concentration in the obese men was significantly lower than in the control group (18.6 +/- 1.3 vs. 23.3 +/- 1.4 ng L-1; P < 0.01), whereas in the obese women it was significantly higher than in the control group (2.0 +/- 0.2 vs. 1.3 +/- 0.1 ng L-1; P < 0.05). When multiple linear regression was performed without body mass index (BMI) in the statistical model, leptin was correlated with basal insulin (P < 0.0001), insulin sensitivity (P < 0.0001) and T (P < 0.0001) in both men and women. When BMI was included in the model as an independent variable, leptin was significantly correlated only with BMI (P < 0.0001), the degree of insulin resistance (P < 0.05) and T (only in men, P < 0.05). This study confirms that serum leptin is strongly correlated with the degree of obesity and female sex. The negative correlation between leptin and T in men, independent of BMI, is consistent with the hypothesis that T may possess an inhibitory effect on adipocyte ob gene transcription.

Adipose Tissue↗

PubMed1997

Endothelial cell-associated tissue factor pathway inhibitor (TFPI) antigen in severe nondiabetic obese patients: effect of hyperinsulinemia.

It has been suggested that the extrinsic coagulation system plays a crucial role in the initiation of blood coagulation in atherosclerotic disease and that TFPI, the inhibitor of the factor VIIa/tissue factor complex, bound to the endothelial cells, could prevent in vivo blood clotting. Because obesity has a role in the pathogenesis of atherosclerotic cardiovascular disease, we measured TFPI antigen plasma levels (ng/mL) by ELISA at baseline and 5 minutes after an IV bolus of 20 IU/kg body weight of unfractionated commercial mucous heparin in 12 obese patients with a mean body mass index (BMI) of 41.4 +/- 1.4 kg/m2 and 14 normal-weight control subjects (BMI 23.1 +/- 1.3 kg/m2). All subjects were submitted to an OGTT. The obese patients displayed a normal glucose tolerance. However, they had a different glucose-induced hyperinsulinemia (14.9 +/- 2.0 versus 7.8 +/- 0.8 mU/L, p < 0.01). Total serum cholesterol did not differ between controls and obese patients, whereas plasma triglycerides were higher in the latter group. Basal TFPI antigen plasma levels were similar in obese and controls (83.8 +/- 5.0 versus 77.7 +/- 3.5 ng/mL, p = N.S.). In contrast, after heparin a significantly lower rise in TFPI antigen plasma levels was observed in obese patients (511.2 +/- 43.4 ng/mL) (p < 0.003). Moreover, a significant inverse correlation was found between the heparin-stimulated TFPI antigen plasma levels and both BMI and basal plasma insulin concentrations. Thus, the link between insulin level and endothelial cell-associated TFPI could at least partially explain why obese patients are more prone to develop cardiovascular disorders.

Adult↗

PubMed1997

Lactate infusion to normal rats during hyperglycemia enhances in vivo muscle glycogen synthesis.

Both hyperglycemia and hyperinsulinemia stimulate whole body and muscle glucose disposal. To define the impact of increased lactate concentration (4-5 mM) on muscle glucose disposal during hyperglycemia, we studied anesthetized normal rats infused with either sodium lactate or sodium bicarbonate as control. Animals were studied under hyperglycemic clamp (13 mM) using [3-3H]glucose (study 1) and 2-deoxy-[1-3H]glucose (study 2) to assess glucose rate of disappearance (Rd), glycolytic flux (GF), glycogen synthesis, and glucose utilization index by different tissues. Moreover, in study 3, the effect of lactate on the pattern of plasma insulin response to hyperglycemia was evaluated. In study 1, lactate infusion resulted in an increased Rd (38.7 +/- 1.7 vs. 32.3 +/- 1.3 mg.min-1.kg-1; P < 0.01), which was explained by an enhanced rate of glycogen synthesis (23.0 +/- 1.7 vs. 14.7 +/- 1.2 mg.min-1.kg-1; P < 0.001), whereas GF was unchanged. In study 2, lactate-infused animals showed an increased 2-deoxy-glucose disposal and a stimulated glycogen synthase activity as well as an increased glycogen accumulation at the end of the study in several skeletal muscles. In study 3, lactate did not induce any change in either early or late insulin response to hyperglycemia. In conclusion, our results show that muscle glycogen deposition may be enhanced by elevated lactate levels under hyperglycemic conditions and support a role for lactate in the regulation of glucose homeostasis.

Animals↗

PubMed1996

Effect of lactate on hepatic insulin clearance in perfused rat liver.

The aim of our study was to investigate whether sodium lactate has any effect on hepatic insulin dynamics in perfused rat liver. Rat livers were perfused in situ with saline or increasing concentrations of sodium lactate, and hepatic insulin extraction was calculated from the difference in insulin concentration between the portal and the suprahepatic vein. Our results show that hepatic insulin extraction at the three lactate concentrations added was higher than in the control experiments (lactate 1 mmol/l: 263 +/- 51 vs. 765 +/- 114, P < 0.005; lactate 5 mmol/l: 341 +/- 80 vs. 906 +/- 109; P < 0.005; lactate 15 mmol/l: 438 +/- 21 vs. 981 +/- 66 microIU.g-1.30 min-1, P < 0.005). No significant differences were observed in net glucose balance across the liver during perfusion with lactate. Moreover perfused liver displayed a net lactate production during infusion with saline or lactate added at the lower concentrations (1 and 5 mM), whereas at the highest (15 mM), a net lactate uptake by the liver was observed (P < 0.05). Our results suggest that, in perfused rat liver, lactate may increase hepatic insulin clearance. Thus energy fuels such as lactate and nonesterified fatty acid have opposite effects on hepatic insulin clearance and may therefore contribute to the regulation of posthepatic insulin delivery.

Animals↗

PubMed1994

Induction and reversibility of an obesity syndrome by intracerebroventricular neuropeptide Y administration to normal rats.

Intracerebroventricular neuropeptide Y (NPY) administration to normal rats for 7 days produced a sustained, threefold increase in food intake, resulting in a body weight gain of more than 40 g. Basal plasma insulin and triglyceride levels were increased in NPY-treated compared to vehicle-infused rats by about four- and two-fold, respectively. The glucose utilization index of white adipose tissue, measured by the labelled 2-deoxy-D-glucose technique was four times higher in NPY-treated rats compared to controls. This change was accompanied by an increase in the insulin responsive glucose transporter protein (GLUT 4). In marked contrast, muscle glucose utilization was decreased in NPY-treated compared to vehicle-infused animals. This change was accompanied by an increase in triglyceride content. When NPY-treated rats were prevented from overeating, there was no decrease in muscle glucose uptake, nor was there an increase in muscle triglyceride content. This suggests that muscle insulin resistance of ad libitum-fed NPY-treated rats is due to a glucose-fatty acid (Randle) cycle. When intracerebroventricular NPY administration was stopped and rats kept without any treatment for 7 additional days, all the abnormalities brought about by the neuropeptide were normalized. A tonic central effect of NPY is therefore needed to elicit and maintain most of the hormonal and metabolic abnormalities observed in the present study. Such abnormalities are analogous to those seen in the dynamic phase of obesity syndromes in which high hypothalamic NPY levels have been reported.

Adipose Tissue↗

PubMed1994

Effect of naltrexone treatment on insulin secretion, insulin action and postprandial thermogenesis in obesity.

For many years a series of studies has been carried out to evaluate the role of endogenous opioid peptides on glucose metabolism. In this work we studied the influence of endogenous opioid peptides on insulin response to OGTT and glucose-induced thermogenesis before and after a prolonged oral treatment with Naltrexone (50 mg/daily for 6 days), an opioid receptor antagonist, in a group of 9 obese subjects. Moreover in obese patients we evaluated the effect of this anti-opioid drug on insulin secretion and insulin sensitivity during an IVGTT using the minimal model approach. We compared the pre-treatment results with data coming from a group of 5 normal-weight subjects. We measured blood glucose, plasma insulin and C-peptide concentrations and evaluated the following parameters: first (phi 1) and second (phi 2) phase of beta-cell sensitivity, insulin sensitivity and glucose effectiveness. Obese subjects displayed an increased insulin response to oral and i.v. glucose load, due to an increased first phase of insulin secretion (phi 1), a reduced insulin sensitivity (Si) and glucose effectiveness (Sg) in respect to normal-weight subjects. They showed no difference in glucose and insulin area during oral load and in their profiles during i.v. glucose load after naltrexone treatment. Similarly no significant variation in insulin sensitivity and glucose effectiveness was observed. The glucose-induced thermogenesis, measured by indirect calorimetry, was not modified by naltrexone. Therefore our study demonstrates that endogenous opioids do not play any role in the impairment of peripheral insulin sensitivity and energy expenditure in human obesity.

Adult↗

PubMed1994

Effect of endogenous organic hyperinsulinaemia on blood pressure and serum triglycerides.

Hyperinsulinaemia and insulin resistance have been hypothesized to be the common pathophysiological factor of hypertension, NIDDM and obesity. To evaluate the possible role of hyperinsulinaemia and insulin resistance on hypertension, we studied a group of 37 patients with insulinoma who were admitted to our department in the period from 1966 to 1990. We recorded blood pressure and assayed blood glucose, plasma insulin, plasma triglycerides and serum uric acid levels, before and after surgery, in these patients and in a 37-subject control group. No significant increase in blood pressure and triglyceride plasma levels was recorded in the chronic hyperinsulinaemic hypoglycaemic patients, suggesting the lack of a direct role of hyperinsulinaemia on hypertension.

Adult↗

PubMed1994

Insulin resistance and hypertension: studies in transgenic hypertensive TGR(mREN-2)27 rats.

The link between hyperinsulinemia and hypertension is imperfectly understood. Recently, a renin gene (the mouse DBA/REN-2d gene) has been transfected into rats, leading to high blood pressure in transgene-positive animals, TGR(mREN-2)27 rats. We tested whether heterozygous hypertensive TGR(mREN-2)27 rats presented evidence of insulin resistance in comparison with the parent strain of Sprague-Dawley rats. Despite their higher blood pressure (203 +/- 8 vs. 112 +/- 6 mmHg, P < 0.001), transgenic rats had normal fasting levels of plasma glucose, insulin, free fatty acids, and triglycerides and had normal fasting rates of hepatic glucose production (by [14C]glucose infusion). During a euglycemic hyperinsulinemic clamp (3 mU/min), stimulation of whole body glucose utilization was equivalent in transgenic and control animals (12.6 +/- 0.6 vs. 10.9 +/- 1.0 mg.min-1.kg-1, respectively). Likewise, suppression of hepatic glucose output by insulin was complete in both groups. The glucose utilization index (as measured by the 2-deoxy-D-[3H]glucose technique) was similar between transgenic and control animals in several skeletal muscles (soleus, extensor digitorum longus, tibialis, diaphragm, white and red quadriceps, and white and red gastrocnemius), in white adipose tissue (periovarian and inguinal), and in brown adipose tissue. We conclude that single gene hypertension does not alter whole body and individual tissue insulin sensitivity.

Adipose Tissue↗

PubMed1994

Intracerebroventricular administration of neuropeptide Y to normal rats has divergent effects on glucose utilization by adipose tissue and skeletal muscle.

Given that several genetically obese rodents characterized by hyperphagia, hyperinsulinemia, and insulin resistance have increased hypothalamic neuropeptide Y (NPY) mRNA and peptide content, the impact of NPY administered intracerebroventricularly (i.c.v.) for 7 days to normal, awake rats was investigated. NPY produced marked hyperphagia, increased body weight gain, increased basal insulinemia, and, more importantly, a much greater insulin response to meal feeding than that of saline-infused controls. NPY administration also resulted in a pronounced increase in the in vivo insulin-stimulated glucose uptake by adipose tissue but in a marked decrease in uptake by eight different muscle types. Increased insulin responsiveness of the glucose transport process by adipose tissue was accompanied by increases in both GLUT4 mRNA and protein levels. In contrast, the decreased insulin responsiveness of glucose uptake in muscles from NPY-administered rats was not related to GLUT4 expression. We conclude that i.c.v. NPY administration to normal rats produces a hormonal-metabolic situation that is similar to that reported in the dynamic phase of the genetic obesity of the fa/fa strain. Thus, NPY could be of primary importance in the establishment of obesity syndromes with incipient insulin resistance.

Adipose Tissue↗

PubMed1993

Lipolytic effect of beta-endorphin in human fat cells.

Recently, a role of beta-Endorphin on peripheral tissue metabolism has been suggested. A lipolytic effect of beta-Endorphin has been observed both in vivo and in vitro in animals but, at present, there is no evidence for a similar effect in humans. In this study, we investigated the lipolytic effect of beta-Endorphin in isolated human adipocytes. beta-Endorphin induced a significant increase in glycerol release in isolated human fat cells. Naloxone was able to inhibit the beta-Endorphin-induced lipolysis. The opioid antagonist alone had no effect on basal lipolysis and on Epinephrine-stimulated lipolysis when administered together with this hormone. Our results suggest that beta-Endorphin may play a role on lipolysis also in human fat cells and that this effect may be mediated by a specific opiate receptor.

Adipose Tissue↗