Dietary fructose, fruits, fruit juices and glucose tolerance status in Japanese-Brazilians

Background and aims: Evidence suggests that fructose and sweetened beverages may be a risk factor for obesity and type 2 diabetes, but the role of sweetened fruit juices in glucose disturbances has been minimally explored. The aim of this study was to examine the association of total fructose, fresh fruit and sweetened fruit juice intake with glucose tolerance homeostasis in Japanese-Brazilians. Methods and results: A total of 475 men and 579 women aged >= 30 years were evaluated in a cross-sectional population-based survey with a standardized protocol including a 2-h oral glucose tolerance test (WHO criteria). Habitual food consumption was obtained using a validated food frequency questionnaire for Japanese-Brazitians. After adjustments for potential confounding variables, the odds ratio (OR; 95%Cl) for impaired glucose tolerance was 2.1 (1.0-4.5; P for trend = 0.05) for the highest as compared to the lowest tertile intake of total fructose and 2.3 (1.1-5.1; P for trend = 0.05) for the highest as compared to the lowest tertile intake of sweetened fruit juices. Conclusion: Our results showed that high intakes of dietary fructose and sweetened fruit juices, but not whole fresh fruits, were associated with impaired glucose tolerance among genetically susceptible individuals. (C) 2008 Elsevier B.V. All rights reserved.

Dietary omega-3 fatty acid and omega-3: omega-6 fatty acid ratio predict improvement in glucose disturbances in Japanese Brazilians

Objective: We investigated whether lifestyle-induced changes in dietary fat quality are related to Improvements on glucose metabolism disturbances in Japanese Brazilians at high risk of type 2 diabetes Methods: One hundred forty-eight first- and second-generation subjects with impaired glucose tolerance or impaired fasting glycemia who attended a lifestyle intervention program for 12 mo were studied in the city of Bauru. State of Sao Paulo, Brazil Dietary fatty acid intakes at baseline and after 12 mo were estimated using three 24-h recalls. The effect of dietary fat intake on glucose metabolism was investigated by multiple logistic regression models Results: At baseline, mean standard deviation age and body mass index were 60 II y and 25 5 4.2 kg/m2, respectively After 12 mo. 92 subjects had normal plasma glucose levels and 56 remained in prediabetic conditions. Using logistic regression models adjusted for age, gender, generation, basal intake of explanatory nutrient, energy intake, physical activity, and waist circumference, the odds ratios (95% confidence intervals) for reversion to normoglycemia were 3 14 (1 22-8 10) in the second wrote of total w-3 fatty acid, 4 26 (1.34-13 57) in the second tunic of eicosapentaenoic acid, and 280 (1 10-7.10) in the second tertile of linolenic acid. Similarly. subjects in the highest wrote of w-3.w-6 fatty acid ratio showed a higher chance of improving glucose disturbances (2 51, 1.01-6.37) Conclusions: Our findings support the evidence of an independent protective effect of omega-3 fatty acid and of a higher omega-3:omega-6 fatty acid ratio on the glucose metabolism of high-risk individuals (C) 2010 Elsevier Inc All rights reserved.

Nutritional intervention programme among a Japanese-Brazilian community: procedures and results according to gender

Objective: To describe the results of a nutritional intervention programme among Japanese-Brazilians according to gender. Design: A non-controlled experimental study. Setting: The research included three points of clinical, nutritional and physical activity evaluation: at baseline (in 2005), after the first year and at the end of the second year (in 2007). The paired Student t test and multiple linear regression analysis were used to evaluate changes in the subjects` profile (clinical, nutritional and physical activity variables). Subjects: Japanese-Brazilians (n 575) of both genders, aged over 30 years. Results: We verified statistically significant reductions in body weight (0.9 kg), waist circumference (2.9 cm), blood pressure, fasting blood glucose (>3 mg/dl) and total cholesterol (>20 mg/dl) and its fractions, in both genders. We also found reductions in intake of energy (among men), protein (among women) and fat (both genders) and increases in intake of total fibre (among women) and carbohydrate (among men). Conclusions: The intervention programme indicated meaningful benefits for the intervention subjects, with changes in their habits that led to a `healthier` lifestyle positively impacting their nutritional and metabolic profile.

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.

Progression of Diet-Induced Diabetes in C57BL6J Mice Involves Functional Dissociation of Ca(2+) Channels From Secretory Vesicles

OBJECTIVE The aim of the study was to elucidate the cellular mechanism underlying the suppression of glucose-induced insulin secretion in mice fed a high-fat diet (HFD) for 15 weeks. RESEARCH DESIGN AND METHODS-C57BL6J mice were fed a HFD or a normal diet (ND) for 3 or 15 weeks. Plasma insulin and glucose levels in vivo were assessed by intraperitoneal glucose tolerance test. Insulin secretion in vitro was studied using static incubations and a perfused pancreas preparation. Membrane currents, electrical activity, and exocytosis were examined by patch-clamp technique measurements. Intracellular calcium concentration ([Ca(2+)](i)) was measured by microfluorimetry. Total internal reflection fluorescence microscope (TIRFM) was used for optical imaging of exocytosis and submembrane depolarization-evoked [Ca(2+)](i). The functional data were complemented by analyses of histology and gene transcription. RESULTS After 15 weeks, but not 3 weeks, mice on HFD exhibited hyperglycemia and hypoinsulinemia. Pancreatic islet content and beta-cell area increased 2- and 1.5-fold, respectively. These changes correlated with a 20-50% reduction of glucose-induced insulin secretion (normalized to insulin content). The latter effect was not associated with impaired electrical activity or [Ca(2+)](i) signaling. Single-cell capacitance and TIRFM measurements of exocytosis revealed a selective suppression (>70%) of exocytosis elicited by short (50 ms) depolarization, whereas the responses to longer depolarizations were (500 ms) less affected. The loss of rapid exocytosis correlated with dispersion of Ca(2+) entry in HFD beta-cells. No changes in gene transcription of key exocytotic protein were observed. CONCLUSIONS HFD results in reduced insulin secretion by causing the functional dissociation of voltage-gated Ca(2+) entry from exocytosis. These observations suggest a novel explanation to the well-established link between obesity and diabetes. Diabetes 59:1192-1201, 2010

Enalapril treatment corrects the reduced response to bradykinin in diabetes increasing the B2 protein expression

Considering the growing importance of the interaction between components of kallikreinkinin and renin-angiotensin systems in physiological and pathological processes, particularly in diabetes mellitus, the aim of the present study was to investigate the effect of enalapril on the reduced response of bradykinin and on the interaction between angiotensin-(1-7) (Ang-(1-7)) and bradykinin (BK), important components of these systems, in an insulin-resistance model of diabetes. For the above purpose, the response of mesenteric arterioles of anesthetized neonatal streptozotocin-induced (n-STZ) diabetic and control rats was evaluated using intravital microscopy. In n-STZ diabetic rats, enalapril treatment restored the reduced response to BK but not the potentiation of BK by Ang-(1-7) present in non-diabetic rats. The restorative effect of enalapril was observed at a dose that did not correct the altered parameters induced by diabetes such as hyperglycernia, glicosuria, insulin resistance but did reduce the high blood pressure levels of n-SZT diabetic rats. There was no difference in mRNA and protein expressions of B1 and B2 kinin receptor subtypes between n-STZ diabetic and control rats. Enalapril treatment increased the B2 kinin receptor expression. From our data, we conclude that in diabetes enalapril corrects the impaired BK response probably by increasing the expression of B2 receptors. The lack of potentiation of BK by Ang-(1-7) is not corrected by this agent. (c) 2008 Elsevier Inc. All rights reserved.

Long-term intermittent feeding, but not caloric restriction, leads to redox imbalance, insulin receptor nitration, and glucose intolerance

Calorie restriction is a dietary intervention known to improve redox state, glucose tolerance, and animal life span. Other interventions have been adopted as study models for caloric restriction, including nonsupplemented food restriction and intermittent, every-other-day feedings. We compared the short- and long-term effects of these interventions to ad libitum protocols and found that, although all restricted diets decrease body weight, intermittent feeding did not decrease intra-abdominal adiposity. Short-term calorie restriction and intermittent feeding presented similar results relative to glucose tolerance. Surprisingly, long-term intermittent feeding promoted glucose intolerance, without a loss in insulin receptor phosphorylation. Intermittent feeding substantially increased insulin receptor nitration in both intra-abdominal adipose tissue and muscle, a modification associated with receptor inactivation. All restricted diets enhanced nitric oxide synthase levels in the insulin-responsive adipose tissue and skeletal muscle. However, whereas calorie restriction improved tissue redox state, food restriction and intermittent feedings did not. In fact, long-term intermittent feeding resulted in largely enhanced tissue release of oxidants. Overall, our results show that restricted diets are significantly different in their effects on glucose tolerance and redox state when adopted long-term. Furthermore, we show that intermittent feeding can lead to oxidative insulin receptor inactivation and glucose intolerance. (C) 2011 Elsevier Inc. All rights reserved.

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.

Augmentation of insulin secretion by leucine supplementation in malnourished rats: possible involvement of the phosphatidylinositol 3-phosphate kinase/mammalian target protein of rapamycin pathway

A regimen of low-protein diet induces a reduction of pancreatic islet function that is associated with development of metabolic disorders including diabetes and obesity afterward. In the present study, the influence of leucine supplementation on metabolic parameters, insulin secretion to glucose and to amino acids, as well as the levels of proteins that participate in the phosphatidylinositol 3-phosphate kinase (PI3K) pathway was investigated in malnourished rats. Four groups were fed with different diets for 12 weeks: a normal protein diet (17%) without (NP) or with leucine supplementation (NPL) or a low (6%)-protein diet without (LP) or with leucine supplementation (LPL). Leucine was given in the drinking water during the last 4 weeks. As indicated by the intraperitoneal glucose tolerance test, LPL rats exhibited increased glucose tolerance as compared with NPL group. Both NPL and LPL rats had higher circulating insulin levels than controls. The LPL rats also showed increased insulin secretion by pancreatic islets in response to glucose or arginine compared with those observed in islets from LP animals. Glucose oxidation was significantly reduced in NPL, LP, and LPL isolated islets as compared with NP; but no alteration was observed for leucine and glutamate oxidation among the 4 groups. Western blotting analysis demonstrated increased PI3K and mammalian target protein of rapamycin protein contents in LPL compared with LP islets. A significant increase in insulin-induced insulin receptor substrate I associated PI3K activation was also observed in LPL compared with LP islets. These findings indicate that leucine supplementation can augment islet function in malnourished rats and that activation of the PI3K/maminalian target protein of rapamycin pathway may play a role in this process. (C) 2010 Elsevier Inc. All rights reserved.

Vascular endothelial growth factor (VEGF) and VEGF-receptor expression in placenta of hyperglycemic pregnant women

Hyperglycemia occurs in a variety of conditions such as overt diabetes, gestational diabetes and mild hyperglycemia, all of which are generally defined based on the oral glucose tolerance test and glucose profiles. Whereas diabetes has received considerable attention in recent decades, few studies have examined the mechanisms of mild hyperglycemia and its associated disturbances. Mild gestational hyperglycemia is associated with macrosomia and a high risk of perinatal mortality. Morphologically, the placenta of these women is characterized by an increase in the number of terminal villi and capillaries, presumably as part of a compensatory mechanism to maintain homeostasis at the maternal-fetal interface. In this study, we analised the expression of VEGF and its receptors VEGFR-1 (Flt-1) and VEGFR-2 (KDR) in placentas from mildly hyperglycemic women. This expression was compared with that of normoglycemic women and women with gestational and overt diabetes. Immunohistochemistry revealed strong staining for VEGF and VEGFR-2 in vascular and trophoblastic cells of mildly hyperglycemic women, whereas the staining for VEGFR-1 was discrete and limited to the trophoblast. The pattern of VEGF and VEGF-receptor reactivity in placentas from women with overt diabetes was similar to that of normoglycemic women. In women with gestational diabetes, strong staining for VEGFR-1 was observed in vascular and trophoblastic cells whereas VEGF and VEGFR-2 were detected only in the trophoblast. The expression of these proteins was confirmed by western blotting, which revealed the presence of an additional band of 75 kDa. In the decidual compartment, only extravillous trophoblast reacted with all antibodies. Morphological analysis revealed collagen deposition around large arteries in all groups with altered glycemia. These findings indicate a placental response to altered glycemia that could have important consequences for the fetus. The change in the placental VEGF/VEGFR expression ratio in mild hyperglycemia may favor angiogenesis in placental tissue and could explain the hypercapillarization of villi seen in this gestational disturbance. (C) 2010 Elsevier Ltd. All rights reserved.

Chlorpropamide treatment restores the reduced carrageenan-induced paw edema and pleural exudate volume in diabetic rats

Objective and design: Knowing that hyperglycemia is a hallmark of vascular dysfunction in diabetes and that neonatal streptozotocin-induced diabetic rats (n-STZ) present reduced inflammatory response, we decided to evaluate the effect of chlorpropamide-lowered blood glucose levels on carrageenan-induced rat paw edema and pleural exudate in n-STZ. Materials: Diabetes was induced by STZ injection (160 mg/kg, ip) in neonates (2-day-old) Wistar rats. Treatment: n-STZ diabetic rats were treated with chlorpropamide (200 mg/kg, 15 d, by gavage) 8 weeks after STZ injection. Methods: Carrageenan-induced paw edema and pleural exudate volumes were assessed concomitantly with peripheral and exudate leukocyte count. We also evaluated the expression of inducible nitric oxide synthase (iNOS) in lungs of all experimental groups. Results: Chlorpropamide treatment improved glucose tolerance, beta-cell function (assessed by HOMA-beta), corrected paw edema, and pleural exudate volume in n-STZ. Neither leukocyte count nor iNOS expression were affected by diabetes or by chlorpropamide treatment. Conclusion: Chlorpropamide treatment by restoring beta-cell function, reducing blood sugar levels, and improving glucose tolerance might be contributing to the correction of the reduced inflammatory response tested as paw edema and pleural exudate in n-STZ diabetic rats.

Dipeptidyl peptidase IV inhibition attenuates blood pressure rising in young spontaneously hypertensive rats

Objectives The present study aimed to assess the effect of the specific dipeptidyl peptidase IV (DPPIV) inhibitor sitagliptin on blood pressure and renal function in young prehypertensive (5-week-old) and adult spontaneously hypertensive rats (SHRs; 14-week-old). Methods Sitagliptin (40 mg/kg twice daily) was given by oral gavage to young (Y-SHR + IDPPIV) and adult (A-SHR R IDPPIV) SHRs for 8 days. Kidney function was assessed daily and compared with age-matched vehicle-treated SHR (Y-SHR and A-SHR) and with normotensive Wistar-Kyoto rats (Y-WKY and A-WKY). Arterial blood pressure was measured in these animals at the end of the experimental protocol. Additionally, Na(+)/H(+) exchanger isoform 3 (NHE3) function and expression in microvilli membrane vesicles were assessed in young animals. Results Mean arterial blood pressure of Y-SHR + IDPPIV was significantly lower than that of Y-SHR (104 +/- 3 vs. 123 +/- 5 mmHg, P < 0.01) and was similar to Y-WKY (94 +/- 4 mmHg, P > 0.05). Compared to Y-SHR, Y-SHR + IDPPIV exhibited enhanced cumulative urinary flow and sodium excretion and decreased NHE3 activity and expression in proximal tubule microvilli. In the A-SHR, sitagliptin treatment had no significant effect on either renal function or arterial blood pressure. Conclusion Our data suggest that DPPIV inhibition attenuates blood pressure rising in young prehypertensive SHRs, partially by inhibiting NHE3 activity in renal proximal tubule. J Hypertens 29:520-528 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Biodritin microencapsulated human islets of langerhans and their potential for type 1 diabetes mellitus therapy

Background. Microencapsulation of pancreatic islets with polymeric compounds constitutes an attractive alternative therapy for type 1 diabetes mellitus. The major limiting factor is the availability of a biocompatible and mechanically stable polymer. We investigated the potential of Biodritin, a novel polymer constituted of alginate and chondroitin sulfate, for islet microencapsulation. Methods. Biodritin microcapsules were obtained using an air jet droplet generator and gelated with barium or calcium chloride. Microencapsulated rat insulinoma RINm5F cells were tested for viability using the [3-(4,5-dimetyl-thiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide] [MTT] colorimetric assay. Microencapsulated rat pancreatic islets were coincubated with macrophages derived from mouse peritoneal liquid to assess the immunomodulatory potential of the microcapsules, using quantitative real time-PCR (qPCR). Biodritin biocompatibility was demonstrated by subcutaneous injection of empty microcapsules into immunocompetent Wistar rats. Insulin secretion by microencapsulated human pancreatic islets was evaluated using an electrochemoluminescent assay. Microencapsulated human islets transplanted into chemically induced diabetic mice were monitored for reversal of hyperglycemia. Results. The metabolic activity of microencapsulated RINm5F cells persisted for at least 15 days. Interleukin-1 beta expression by macrophages was observed during coculture with islets microencapsulated with Biodritin-CaCl2, but not with Biodritin-BaCl2. No statistical difference in glucose-stimulated insulin secretion was observed between nonencapsulated and microencapsulated islets. Upon microencapsulated islet transplantation, the blood glucose level of diabetic mice normalized; they remained euglycemic for at least 60 days, displaying normal oral glucose tolerance tests. Conclusion. This study demonstrated that Biodritin can be used for islet microencapsulation and reversal of diabetes; however, further investigations are required to assess its potential for long-term transplantation.

High sodium intake enhances insulin-stimulated glucose uptake in rat epididymal adipose tissue

Objective: This study investigated the effect of different sodium content diets on rat adipose tissue carbohydrate metabolism and insulin sensitivity. Methods and Procedures: Male Wistar rats were fed on normal- (0.5% Na+; NS), high- (3.12% Na+; HS), or low-sodium (0.06% Na+; LS) diets for 3, 6, and 9 weeks after weaning. Blood pressure (BP) was measured using a computerized tail-cuff system. An intravenous insulin tolerance test (ivITT) was performed in fasted animals. At the end of each period, rats were killed and blood samples were collected for glucose and insulin determinations. The white adipose tissue (WAT) from abdominal and inguinal subcutaneous (SC) and periepididymal (PE) depots were weighed and processed for adipocyte isolation and measurement of in vitro rates of insulin-stimulated 2-deoxy-d-[H-3]-glucose uptake (2DGU) and conversion of -[U-C-14]-glucose into (CO2)-C-14. Results: After 6 weeks, HS diet significantly increased the BP, SC and PE WAT masses, PE adipocyte size, and plasma insulin concentration. The sodium dietary content did not influence the whole-body insulin sensitivity. A higher half-maximal effective insulin concentration (EC50) from the dose - response curve of 2DGU and an increase in the insulin-stimulated glucose oxidation rate were observed in the isolated PE adipocytes from HS rats. Discussion: The chronic salt overload enhanced the adipocyte insulin sensitivity for glucose uptake and the insulin-induced glucose metabolization, contributing to promote adipocyte hypertrophy and increase the mass of several adipose depots, particularly the PE fat pad.

Smad5 regulates Akt2 expression and insulin-induced glucose uptake in L6 myotubes

Insulin-induced glucose uptake by skeletal muscle results from Akt2 activation and is severely impaired during insulin resistance Recently, we and others have demonstrated that BMP9 improves glucose homeostasis in diabetic and non-diabetic rodents. However, the mechanism by which BMP9 modulates insulin action remains unknown. Here we demonstrate that Smad5. a transcription factor activated by BMP9, and Akt2. are upregulated in differentiated L6 myotubes. Smad5, rather than Smad1/8, is downregulated ""in vivo"" and ""in vitro"" by dexamethasone Smad5 knockdown decreased Akt2 expression and serine phosphorylation and insulin-induced glucose uptake, and increased the expression of the lipid phosphatase Ship2. Additionally, binding of Smad5 to Akt2 gene is decreased in dexamethasone-treated rats and Increased in L6 myotubes compared to myoblasts The present study indicates that Smad5 regulates glucose uptake in skeletal muscle by controlling Akt2 expression and phosphorylation These finding reveals Smad5 as a potential target for the therapeutic of type 2 diabetes. (C) 2010 Elsevier Ireland Ltd. All rights reserved.