Adiponectin: serum levels, promoter polymorphism, and associations with birth size and cardiometabolic outcome in young adults born large for gestational age

Objective: To assess whether the -11391G > A polymorphism in the regulatory region of the adiponectin gene (ADIPOQ) is associated with birth size, postnatal growth, adiponectinemia, and cardiometabolic risk in adult life. Design: Case-control study nested within a prospective cohort of 2063 community subjects born in 1978/1979 and followed since birth to date. Methods: ADIPOQ -11391G > A genotype-phenotype associations were evaluated in 116 subjects born large for gestational age (LGA) and 392 gender-matched controls at birth (birth size), at 8-10 years (catch-down growth), and at 23-25 years of age (cardiometabolic profile). Results: The -11391A variant allele frequency was higher in LGA subjects (P=0.04). AA genotype was associated with augmented probability of being born LGA (odds ratio=4.14; 95% confidence interval: 1.16-16.7; P=0.03). This polymorphism was associated neither with body composition nor with postnatal growth pattern. At the age of 23-25 years, the -11391A variant allele was associated with higher serum adiponectin levels (GG: 10.7 +/- 6.2 versus GA: 12.2 +/- 6.5 versus AA: 14.2 +/- 6.8 mu g/ml; P < 0.01). Subjects born LGA presented higher body mass index (BMI; P=0.01), abdominal circumference (P=0.04), blood pressure (P=0.04), and homeostasis assessment model for insulin resistance (P=0.01) than adequate for gestational age. Symmetry at birth did not influence these variables. The occurrence of catch-down of weight was associated with lower BMI and abdominal circumference (P < 0.001) at 23-25 years. Conclusions: The -11391A ADIPOQ gene variant was associated with increased chance of being born LGA and with higher adiponectin levels in early adult life.

The role of nutritional profile in the orexigenic neuropeptide secretion in nonalcoholic fatty liver disease obese adolescents

Background Little progress has been made to identify the central neuroendocrine pathway involved in the energy intake control in nonalcoholic fatty liver disease (NAFLD) patients. Objective To assess the influence of orexigenic neuropeptides in the nutritional aspects of NAFLD obese adolescents submitted to a long-term interdisciplinary approach. Methods Fifty adolescents aged 15-19 years, with body mass index at least 95th percentile, consisting of 25 patients without NAFLD and 25 with NAFLD. The NAFLD diagnosis was determined by ultrasonography. Blood samples were collected to analyze glycemia, hepatic transaminases, and lipid profile. Insulin resistance was estimated by Homeostasis Model Assessment Insulin Resistance Index. Neuropeptide Y (NPY) and agouti related protein concentrations were measured by enzyme-linked immunosorbent assay. Analyses of food intake were made by 3 days recordatory inquiry. Results At baseline conditions, the patients with NAFLD had significantly higher values of body mass, body mass index, visceral fat, triglycerides, VLDL-C, and hepatic transaminases. After the long-term intervention, they presented a significant reduction in these parameters. In both the groups, it was observed a significant decrease in energy intake, macronutrients and dietetic cholesterol. Only the patients with NAFLD presented a positive correlation between the saturated fatty acids intake and the orexigenic neuropeptides NPY and agouti related protein, and carbohydrate with NPY. Indeed, it was observed a positive correlation between energy intake, lipid (%) and saturated fatty acids with visceral fat accumulation. Conclusion Our findings showed an important influence of diet composition in the orexigenic system, being essential consider that the excessive saturated fatty acids intake could be a determinant factor to increase nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 22:557-563 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Progression of Lipid Peroxidation Measured as Thiobarbituric Acid Reactive Substances, Damage to DNA and Histopathological Changes in the Liver of Rats Subjected to a Methionine-Choline-Deficient Diet

Methionine-choline-deficient diet represents a model for the study of the pathogenesis of steatohepatitis. Male rats were divided into three groups, the first group receiving a control diet and the other two groups receiving a methionine-choline-deficient diet for 1 month (MCD1) and for 2 months (MCD2), respectively. The livers of the animals were collected for the determination of vitamin E, thiobarbituric acid reactive substances (TBARS), GSH concentration, DNA damages, and for histopathological evaluation. The hepatic TBARS and GSH content was higher (P < 0.05) in the groups receiving the experimental diet (MCD1 and MCD2) compared to control diet, and hepatic vitamin E concentration differed (P < 0.05) between the MCD1 and MCD2 groups, with the MCD2 group presenting a lower concentration. Damage to hepatocyte DNA was greater (P < 0.05) in the MCD2 group (262.80 DNA injuries/100 hepatocytes) compared to MCD1 (136.4 DNA injuries/100 hepatocytes) and control diet (115.83 DNA injuries/100 hepatocytes). Liver histopathological evaluation showed that steatosis, present in experimental groups was micro- and macro-vesicular and concentrated around the centrolobular vein, zone 3, with preservation of the portal space. The inflammatory infiltrate was predominantly periductal and the steatosis and inflammatory infiltrate was similar in the MCD1 and MCD2 groups, although the presence of Mallory bodies was greater in the MCD2 group. The study describes the contribution of a methionine-choline-deficient diet to the progression of steatosis, lipid peroxidation and hepatic DNA damage in rats, serving as a point of reflection about the role of these nutrients in the western diet and the elevated non-alcoholic steatohepatitis rates in humans.

Prevalence and risk factors of metabolic syndrome in Brazilian and Italian obese adolescents: a comparison study

Background: Metabolic syndrome (MS) prevalence between different populations in obese adolescents is scanty to date. Objective: To compare the MS prevalence and related risk factors in Brazilian and Italian obese adolescents. Methods: A total of 509 adolescents (110 Brazilian, 399 Italian), aged 15-19 years. Anthropometric characteristics, triglycerides (TG), total, low-density lipoprotein (LDL)-, high-density lipoprotein (HDL)-cholesterol, fasting plasma glucose (FPG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and blood pressure were measured. Results: Age, body mass index (BMI) and BMI z-score were not significantly different between the two subgroups. BMI z-score, TG, FPG, HOMA-IR and systolic blood pressure (SBP) were significantly higher in boys than in girls both in Brazilian and Italian adolescents, while HDL-cholesterol levels were lower in boys than in girls. No significant differences were observed in BMI, LDL and total-cholesterol and DBP in two genders and groups. Insulin, FPG, HOMA-IR and TG were significantly higher, while LDL-cholesterol and SBP were significantly lower in Brazilian than in Italian subjects, both in males and females. HDL and total-cholesterol and diastolic blood pressure (DBP) were not significantly different between the two subgroups and genders. MS prevalence was higher in Brazilian than in Italian obese boys (34.8 vs. 23.6%, p < 0.001) and girls (15.6 vs. 12.5%, p < 0.01). The most frequently altered parameter was HOMA-IR both in subjects with MS (100% in Brazilian and 81.8% in Italian) and without MS (42.9% and 11.7%). Conclusion: Metabolic syndrome represents a worldwide emerging health problem in different ethnical populations, the alterations of the risk factors related to MS (different in their prevalence between different subgroups) being strictly linked to the degree of obesity.

High doses of dexamethasone induce increased beta-cell proliferation in pancreatic rat islets

Rafacho A, Cestari TM, Taboga SR, Boschero AC, Bosqueiro JR. High doses of dexamethasone induce increased beta-cell proliferation in pancreatic rat islets. Am J Physiol Endocrinol Metab 296: E681-E689, 2009. First published January 21, 2009; doi:10.1152/ajpendo.90931.2008.-Activation of insulin signaling and cell cycle intermediates is required for adult beta-cell proliferation. Here, we report a model to study beta-cell proliferation in living rats by administering three different doses of dexamethasone (0.1, 0.5, and 1.0 mg/kg ip, DEX 0.1, DEX 0.5, and DEX 1.0, respectively) for 5 days. Insulin sensitivity, insulin secretion, and histomorphometric data were investigated. Western blotting was used to analyze the levels of proteins related to the control of beta-cell growth. DEX 1.0 rats, which present moderate hyperglycemia and marked hyperinsulinemia, exhibited a 5.1-fold increase in beta-cell proliferation and an increase (17%) in beta-cell size, with significant increase in beta-cell mass, compared with control rats. The hyperinsulinemic but euglycemic DEX 0.5 rats also showed a significant 3.6-fold increase in beta-cell proliferation. However, DEX 0.1 rats, which exhibited the lowest degree of insulin resistance, compensate for insulin demand by improving only islet function. Activation of the insulin receptor substrate 2/phosphatidylinositol 3-kinase/serine-threoninekinase/ribosomalprotein S6 kinase pathway, as well as protein retinoblastoma in islets from DEX 1.0 and DEX 0.5, but not in DEX 0.1, rats was also observed. Therefore, increasing doses of dexamethasone induce three different degrees of insulin requirement in living rats, serving as a model to investigate compensatory beta-cell alterations. Augmented beta-cell mass involves beta-cell hyperplasia and, to a lower extent, beta-cell hypertrophy. We suggest that alterations in circulating insulin and, to a lesser extent, glucose levels could be the major stimuli for beta-cell proliferation in the dexamethasone-induced insulin resistance.

Increased circulating levels of matrix metalloproteinase (MMP)-8, MMP-9, and pro-inflammatory markers in patients with metabolic syndrome

Background: Metabolic syndrome (MetS) predisposes to cardiovascular complications. Increased concentrations of pro-inflammatory mediators and imbalanced concentrations of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) may reflect the pathophysiology of MetS. We compared the circulating levels of MMPs, TIMPs, and inflammatory mediators in MetS patients with those found in healthy controls. Methods: We studied 25 healthy subjects and 25 MetS patients. The plasma levels of pro-MMP-2 and pro-MMP-9 were determined by gelatin zymography. The plasma concentrations of MMP-8, MMP-3, TIMP-1, TIMP-2, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), intercellular adhesion molecule (sICAM-1), and sP-selectin were measured by ELISA kits. Results: We found higher sP-selectin, sICAM-1, MCP-1, and IL-6 (all P<0.05) concentrations in MetS patients compared with healthy controls. No differences in pro-MMP-2, MMP-3, and TIMP-2 levels were found (all P>0.05). However, we found higher pro-MMP-9, MMP-8. and TIMP-1 levels in MetS patients compared with healthy controls (all P<0.05). Conclusions: Patients with MetS have increased circulating concentrations of pro-MMP-9, MMP-8, and TIMP-1 that are associated with increased concentrations of pro-inflammatory mediators and adhesion molecules. These findings suggest that MMPs may have a role in the increased cardiovascular risk of MetS patients. Pharmacological interventions targeting MMPs, especially MMP-9 and MMP-8 deserve further investigation in MetS patients. (C) 2009 Elsevier B.V. All rights reserved.

Impact of a nutritional counseling program on prevention of HAART-related metabolic and morphologic abnormalities

The advent of highly active antiretroviral therapy (HAART) improved HIV infection prognosis. However, adverse metabolic and morphologic effects emerged, highlighting a lack of investigation into the role of nutritional interventions among this population. The present study evaluated the impact of a nutritional counseling program on prevention of morphologic and metabolic changes in patients living with HIV/AIDS receiving HAART. A 12-month randomized clinical trial was conducted with 53 adults of both genders in use of HAART. Subjects were allocated to either an intervention group (IG) or a control group (CG). Nutritional counseling was based on the promotion of a healthy diet pattern. Anthropometrical, biochemical, blood pressure, and food intake variables were assessed on four separate occasions. Sub scapular skin-fold results showed a significant tendency for increase between time 1 (Mean IG = 14.9 mm; CG = 13.6 mm), time 3 (Mean IG = 16.7 mm; CG = 18.2 mm), and time 4 (Mean IG = 16.4 mm; CG = 17.7 mm). Lipid percentage intake presented a greater increase among controls (time 1 mean = 26.3%, time 4 mean = 29.6%) than among IG subjects (time 1 mean = 29.1%, time 4 mean = 28.9%). Moreover, participants allocated to the IG presented an increase in dietetic fiber intake of almost 10 grams. The proposed nutritional counseling program proved to be effective in improving diet by reducing fat consumption and increasing fiber intake.

Association of genetic variants in the adiponectin encoding gene (ADIPOQ) with type 2 diabetes in Japanese Brazilians

Aim: The objective of this study is to assess the contribution of ADIPOQ variants to type 2 diabetes in Japanese Brazilians. Methods: We genotyped 200 patients with diabetes mellitus (100 male and 100 female, aged 55.0 years [47.5-64.0 years]) and 200 control subjects with normal glucose tolerant (NGT) (72 male and 128 female, aged 52.0 years [43.5-64.5 years]). Results: Whereas each polymorphism studied (T45G, G276T, and A349G) was not significantly associated with type 2 diabetes mellitus, the haplotype GGA was overrepresented in our diabetic population (9.3% against 3.1% in NGT individuals, P=.0003). Also, this haplotype was associated with decreased levels of adiponectin. We also identified three mutations in exon 3: I164T, R221S, and H241P, but, owing to the low frequencies of them, associations with type 2 diabetes could not be evaluated. The subjects carrying the R221S mutation had plasma adiponectin levels lower than those without the mutation (2.10 mu g/ml [1.35-2.55 mu g/ml] vs. 6.68 mu g/ml [3.90-11.23 mu g/ml], P=.015). Similarly, the I164T mutation carriers had mean plasma adiponectin levels lower than those noncarriers (3.73 mu g/ml [3.10-4.35 mu g/ml] vs. 6.68 mu g/ml [3.90-11.23 mu g/ml]), but this difference was not significant (P=.17). Conclusions: We identified in the ADIPOQ gene a risk haplotype for type 2 diabetes in the Japanese Brazilian population. (C) 2010 Elsevier Inc. All rights reserved.

Antiobesity Effects of yerba mate Extract (Ilex paraguariensis) in High-fat Diet-induced Obese Mice

Because the potential of yerba mate (Ilex paraguariensis) has been suggested in the management of obesity, the aim of the present study was to evaluate the effects of yerba mate extract on weight loss, obesity-related biochemical parameters, and the regulation of adipose tissue gene expression in high-fat diet-induced obesity in mice. Thirty animals were randomly assigned to three groups. The mice were introduced to standard or high-fat diets. After 12 weeks on a high-fat diet, mice were randomly assigned according to the treatment (water or yerba mate extract 1.0 g/-kg). After treatment intervention, plasma concentrations of total cholesterol, high-density lipoprotein cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, and glucose were evaluated. Adipose tissue was examined to determine the mRNA levels of several genes such as tumor necrosis factor-alpha (TNF-alpha), leptin, interleukin-6 (IL-6), C-C motif chemokine ligand-2 (CCL2), CCL receptor-2 (CCR2), angiotensinogen, plasminogen activator inhibitor-1 (PAI-1), adiponectin, resistin, peroxisome proliferator-activated receptor-gamma(2) (PPAR-gamma(2)), uncoupling protein-1 (UCP1), and PPAR-gamma coactivator-1 alpha (PGC-1 alpha). The F4/80 levels were determined by immunoblotting. We found that obese mice treated with yerba mate exhibited marked attenuation of weight gain, adiposity, a decrease in epididymal fat-pad weight, and restoration of the serum levels of cholesterol, triglycerides, LDL cholesterol, and glucose. The gene and protein expression levels were directly regulated by the high-fat diet. After treatment with yerba mate extract, we observed a recovery of the expression levels. In conclusion, our data show that yerba mate extract has potent antiobesity activity in vivo. Additionally, we observed that the treatment had a modulatory effect on the expression of several genes related to obesity.

Novel mutation in the adiponectin (ADIPOQ) gene is associated with hypoadiponectinaemia in Japanese-Brazilians

P>Objective Adiponectin is an important mediator of insulin sensitivity, encoded by the ADIPOQ gene. Here we describe two Japanese-Brazilian families with hypoadiponectinaemia due to a novel mutation in ADIPOQ. Design and patients In this study, we examined the entire translated regions of adiponectin in Japanese-Brazilians, a population with one of the highest prevalence rates of diabetes worldwide. We screened 200 patients with type 2 diabetes (DM) and 240 age-matched subjects with normal glucose tolerance. Results A novel heterozygous T deletion at position 186 in exon 2 of ADIPOQ, causing a frameshift at codon 62 and leading to a premature termination at codon 168 (p.Gly63ValfsX106), was found in two individuals with diabetes. This mutation was not found in 240 nondiabetic control subjects. In addition, we screened the mutation in an expanded set of 100 nondiabetic subjects from the general Brazilian population, but we found no mutations. In addition, six family members of the probands were identified as mutation-carriers. Individuals who were mutation-carriers had markedly low plasma adiponectin concentrations compared with those without the mutation [DM: 0 center dot 65 (0 center dot 59-1 center dot 34) mu g/ml vs. 5 center dot 30 (3 center dot 10-8 center dot 55) mu g/ml, P < 0 center dot 0001; normal glucose tolerance: 0 center dot 95 (0 center dot 76-1 center dot 48) mu g/ml vs. 8 center dot 50 (5 center dot 52-14 center dot 55) mu g/ml, P = 0 center dot 003]. All individuals carrying the p.Gly63ValfsX106 mutation and older than 30 years were found to be diabetic. Conclusions We describe for the first time a frameshift mutation in exon 2 of the ADIPOQ gene, which modulates adiponectin levels and may contribute to the genetic risk of late-onset diabetes in Japanese-Brazilians.

The impact of maternal cortisol concentrations on child arterial elasticity

Epidemiological studies suggest that glucocorticoid excess in the fetus may contribute to the pathophysiology of cardiovascular diseases in adulthood. However, the impact of maternal glucocorticoid on the cardiovascular system of the offspring has not been much explored in studies involving humans, especially in childhood. The objective of this study was to assess the influence of maternal cortisol concentrations on child arterial elasticity. One hundred and thirty pregnant women followed from 1997 to 2000, and respective children 5-7 years of age followed from 2004 to 2006 were included in the study. Maternal cortisol was determined in saliva by an enzyme immunoassay utilizing the mean concentration of nine samples of saliva. Arterial elasticity was assessed by the large artery elasticity index (LAEI; the capacitive elasticity of large arteries) by recording radial artery pulse wave, utilizing the equipment HDI/PulseWave CR-2000 Cardiovascular Profiling System (R). The nutritional status of the children was determined by the body mass index (BMI). Insulin concentration was assessed by chemiluminescence, and insulin resistance by the homeostasis model assessment. Blood glucose, total cholesterol and fractions (LDL-c and HDL-c) and triglyceride concentrations were determined by automated enzymatic methods. The association between maternal cortisol and child arterial elasticity was assessed by multivariate linear regression analysis. There was a statistically significant association between maternal cortisol and LAEI (P=0.02), controlling for birth weight, age, BMI and HDL-c of the children. This study suggests that exposure to higher glucocorticoid concentrations in the prenatal period is associated to lower arterial elasticity in childhood, an earlier cardiovascular risk marker.

Microalbuminuria is associated with impaired arterial and venous endothelium-dependent vasodilation in patients with Type 2 diabetes

Background: Microalbuminuria in Type 2 diabetes is associated with arterial endothelial dysfunction, but the venous bed was never evaluated. Aim: To study the endothelial function in the venous and arterial bed in patients with Type 2 diabetes with normoalbuminuria or microalbuminuria. Material and methods: We evaluated 28 patients with Type 2 diabetes, glycated hemoglobin (Hbak(1c)) <7.5%, who were classified as normo- (albuminuria <30 mg/24 h; no.=16) or microalbuminuric (albuminuria 30-300 mg/24 h; no.=12). Venous and arterial endothelial function were assessed by the dorsal hand vein technique (venodilation by acetylcholine) and brachial artery flow-mediated vasodilation, respectively. Results: Patients were normotensive (systolic arterial pressure: 131.1 +/- 10.6 mmHg) and on good metabolic control (HbA(1c): 6.6 +/- 0.6%). Microalbuminuric patients presented impaired venous (32.9 +/- 17.4 vs 59.3 +/- 26.5%; p=0.004) and arterial vasodilation (1.8 +/- 0.9 vs 5.1 +/- 2.4; p<0.001), as compared to normoalbuminuric patients. There was a negative correlation between acetylcholine-induced venodilation and albuminuria (r=-0.62; p<0.001) and HbA(1c) (r=-0.41; p=0.032). The same was observed between flow-mediated arterial vasodilation and albuminuria (r=-0.49; p=0.007) and HbA(1c) (r=-0.44; p=0.019). Venous and arterial vasodilation was positively correlated (r=0.50; p=0.007). Conclusions: Both venous and arterial endothelial function are impaired in Type 2 microalbuminuric diabetics, in spite of good metabolic control, suggesting that other factors are involved in its pathogenesis. (J. Endocrinol. Invest. 33: 696-700, 2010) (C) 2010, Editrice Kurtis

Reduced venous endothelial responsiveness after oral lipid overload in healthy volunteers

The aim of this study was to investigate endothelial venous function, mflammatory markers, and systemic oxidative stress after an oral lipid overload (OLO). We studied 18 healthy adults (9 men; age, 29.2 +/- 0.9 years; body mass index, 22.3 +/- 0.4 kg/m(2)). Blood samples were collected in the fasting state and 3, 4, and 5 hour after the OLO (1000 kcal, 58% fat) for metabolic variables, oxidative stress, inflammatory markers, adiponectin, and resistin. Changes in vein diameter to phenylephrine, acetylcholine, and sodium nitroprusside (dorsal hand vein technique) were measured before and after the OLO. Oral lipid overload increased triglycerides (61 +/- 6 vs 134 +/- 17 mg/dL, P <.001), insulin (7.2 +/- 0.8 vs 10.7 +/- 1.3 mu U/mL, P <.05), and resistin (5.38 +/- 0.5 vs 6.81 +/- 0.7 ng/mL, P <.05) and reduced antioxidant capacity (plasma total antioxidant capacity: 186.7 +/- 56 vs 161.8 +/- 50 U Trolox per microliter plasma, P <.01), vascular reactivity (171.3 +/- 85 vs 894.4 +/- 301 ng/mL, P <.001), and maximum acetylcholine venodilation (105.9% +/- 9% vs 61.0% +/- 7%, P <.05). No changes were observed for sodium nitroprusside. Post-OLO triglycerides were positively correlated with phenylephrine dose (rho = 0.38, P <.05) and resistin (rho = 0.43, P <.01) and negatively correlated with the maximum acetylcholine venodilation (rho = -0.36, P <.05). In conclusion, an OLO impaired venoconstriction responsiveness in healthy subjects, probably because of a reduction in the antioxidant capacity. (C) 2008 Elsevier Inc. All rights reserved.

Androgenicity and venous endothelial function in post-menopausal women

Background: Endothelial dysfunction is one of the early signs of cardiovascular damage. High androgen levels have been related to inflammatory endothelial markers in pre- and post-menopausal women. Aim: This cross-sectional study aimed at investigating whether free androgen index (FAI) [estimated by dividing total testosterone (nmol/l) by SHBG (nmol/l) x 100] is related to endothelial function during post-menopause. Subjects and methods: Twenty-six post-menopausal women were assessed with the dorsal hand vein compliance technique. Acetylcholine (Ach) and sodium nitroprusside (SNP) dose-response curves were constructed to test endothelium-dependent and independent relaxation, respectively. Results: Mean age was 54 yr ( 4) and median time since menopause was 6 yr (interquartile range: 3-9). Patients were stratified according to FAI levels into two groups: FAI greater than or less than the group median of 2.5. Waist-to-hip ratio (WHR) was significantly higher in the group with FAI>2.5, as well as median dose of Ach for maximal vasodilation [720 (360-3600) ng/min with FAI>2.5 vs 36 (0.36-360) ng/min with FAI <= 2.5; p=0.005]. Maximal vasodilation with SNP was similar in both groups. Positive correlations were observed between Ach doses and maximal vasodilation and FAI (r=0.473, p=0.015), waist (r=0.510, p= 0.011), and WHR (r=0.479, p=0.021). SHBG was negatively correlated with Ach doses (rs=-0.400, p=0.043). Conclusions: This study suggests that FAI, even within normal limits, is related to early changes in endothelial function in healthy post-menopausal women. Longitudinal studies are required to determine the clinical relevance of these findings. (J. Endocrinol. Invest. 33: 239-243, 2010) (C) 2010, Editrice Kurtis

Angiotensin II induces superoxide generation via NAD(P)H oxidase activation in isolated rat pancreatic islets

Angiotensin II (Ang II) controls blood pressure, electrolyte balance, cell growth and vascular remodeling. Ang II activates NAD(P)H oxidase in several tissues with important function in the control of insulin secretion. Considering the concomitant occurrence of hypertension, insulin resistance and pancreatic B cell secretion impairment in the development of type II diabetes the aim of the present study was to evaluate the effect of ANG II on NAD(P)H oxidase activation in isolated pancreatic islets. We found that ANGII-induced superoxide generation via NAD(P)H oxidase activation and increased protein and mRNA levels of NAD(P)H oxidase subunits (p47(PHOX) and gp91(PHOX)). (C) 2008 Elsevier B.V. All rights reserved.