The Influence of (Poly)phenol Intake in Saliva Proteome: Short- and Medium-Term Effects of Apple.

The relationship between salivary proteome and dietary habits was studied in previous works, where a relationship between salivary proteins like cystatins and polyphenol/tannin levels in diet was observed. However, it remains to be elucidated if this association results from an effect of polyphenol-rich food ingestion on saliva composition. The aim of this work was to test the effects of apple intake on the saliva proteome, both in the short and medium term (after 4 days of continuous intake). By incubating saliva samples with apple phenolic-rich extract, protein bands containing α-amylase, S-type cystatins, and proline-rich proteins (PRPs) appeared in the fraction that precipitated, showing the potential of these (poly)phenols to precipitate salivary proteins. Among these, it was salivary cystatins that presented changes in their levels both in the saliva samples collected immediately after apple intake and in the ones collected after 4 days of intake of an extra amount of apple. These results support the thought that intake is reflected in the salivary proteome. The effect of a polyphenol-rich food, like the apple, on salivary cystatin levels is in line with results observed in animal models and, due to the involvement of these proteins in oral food perception, it would be interesting to explore in future studies the effect of these changes on sensory perception and acceptance of polyphenol-rich food.

How Individual Variations in the Perception of Basic Tastes and Astringency Relate with Dietary Intake and Preferences for Fruits and Vegetables.

Background: Oral food perception plays a major role in food acceptance, although the way it relates with food preferences and final choices in adults is still debatable. The objective of the present study was to assess the relationship between gustatory function, dietary habits and fruit and vegetable preferences. Methods: Recognition thresholds, suprathreshold and hedonics were accessed for sweet, bitter, sour, salty and astringency in 291 adult participants. A Food Frequency Questionnaire (FFQ) and a questionnaire for assessment of preferences for individual fruit and vegetables were filled by the participants. Results: Three clusters were obtained: "most sensitive", "less sensitive" and "less sensitive only for sour". The less sensitive cluster showed lower preferences for fruit and vegetables and higher intake of sweets and fast foods, whereas higher preferences for sweet veggies were observed in the "most sensitive" cluster. Basic tastes and astringency hedonics did not associate with fruit and vegetable preferences, but the sensitivity for these oral sensations did. Conclusions: Taste and astringency sensitivities are related with the preference for fruit and vegetables, being also associated with some dietary habits. The effectiveness of the strategies to promote plant-based healthy food consumption may benefit from the knowledge of individuals' gustatory function.

Salivary Protein Profile and Food Intake: A Dietary Pattern Analysis.

Saliva research has gained interest due to its potential as a source of biomarkers. One of the factors inducing changes in saliva, in the short term, is food intake, and evidence exist about changes in salivary proteome induced by some food components. Since this topic of research is in its early stages, it was hypothesized that saliva protein composition could be associated with different levels of adherence to dietary patterns that contain higher amounts of plant products. The aim of the present study was to test this hypothesis, in adults, by comparing salivary protein electrophoretic profiles of individuals with different diet characteristics, particularly dietary patterns (DP) that exhibit different proportions of animal and plant-based products. Dietary habits were assessed in 122 adults (61 from each sex, with ages ranging from 20 to 59 years) using Food Frequency Questionnaires. To identify the dietary patterns, a principal component analysis was used. Individual's non-stimulated saliva was evaluated for flow rate, pH, protein concentration, α-amylase activity, and electrophoretic protein profiles. Seven dietary patterns (DP) were identified. Salivary amylase enzymatic activity was positively associated with animal-based and starchy foods DP, and with plant-based fatty foods without wine DP. At the same time, protein bands containing amylase and type S cystatins were positively associated with the cheese/yoghurt and wine DP. Our results support the association of salivary proteomics and different dietary patterns and highlight the need of considering food consumption habits in studies using saliva, since this is a factor associated with variations in the composition of this fluid.

Relationship between Mediterranean Diet Adherence and Saliva Composition.

Dietary polyphenol exposure is known to change protein saliva composition in rodents, but less is known in humans. The present study aimed to assess the relationship between saliva protein composition and adherence to Mediterranean Diet (MD) and polyphenol intake levels. Participants were assessed for their dietary habits, which were converted in Mediterranean adherence level, according to Mediterranean Diet Adherence Score (MEDAS) score. Total polyphenol and total flavanol intakes were extrapolated from dietary data, using Phenol explorer database. Whole saliva was collected, and proteins were separated by SDS-PAGE. Salivary S-type cystatins were highly expressed in the group with medium adherence to MD, being positively correlated with wine intake in overweight individuals. The association between salivary amylase and MD adherence also depended on Body Mass Index (BMI), with a positive association only in normal weight individuals. Polyphenol intake was positively associated with S-type cystatins levels, particularly when flavanols were considered separately. These results show that saliva relationship with MD adherence depend on BMI, suggesting that normal weight and overweight individuals may have different salivary responses to diet. Moreover, these results reinforce the link between saliva and dietary polyphenols (flavanols) levels, leading to the hypothesis that salivary proteome can have a role in polyphenol-rich foods acceptance.

Amelioration of glycemic control by sleeve gastrectomy and gastric bypass in a lean animal model of type 2 diabetes: restoration of gut hormone profile.

BACKGROUND: In obese diabetic patients, bariatric surgery has been shown to induce remission of type 2 diabetes. Along with weight loss itself, changes in gut hormone profiles after surgery play an important role in the amelioration of glycemic control. However, the potential of gastrointestinal surgery regarding diabetes remission in non-severely obese diabetic patients has yet to be defined. In the present experimental study, we explored the effect of established bariatric procedures with and without duodenal exclusion on glycemic control and gut hormone profile in a lean animal model of type 2 diabetes. METHODS: Forty 12- to 14-week-old non-obese diabetic Goto-Kakizaki (GK) rats were randomly assigned to four groups: control group (GKC), sham surgery (GKSS), sleeve gastrectomy (GKSG), and gastric bypass (GKGB). Age-matched Wistar rats served as a non-diabetic control group (WIC). Glycemic control and plasma lipids were assessed at the beginning of the observation period and 4 weeks after surgery. Fasting and mixed meal-induced plasma levels of ghrelin, glucagon-like peptide-17-36 (GLP-1), and peptide tyrosine-tyrosine (PYY) were measured. RESULTS: In GK rats, glycemic control improved after sleeve gastrectomy (SG) and gastric bypass (GB). Mixed meal-induced gut hormone profiles in Wistar rats (WIC) were significantly different from those of sham-operated or control group GK rats. After SG and GB, GK rats showed a similar postprandial decrease in ghrelin as observed in non-diabetic WIC. Following both surgical procedures, a significant meal-induced increase in PYY and GLP-1 could be demonstrated. CONCLUSIONS: SG and GB induce a similar improvement in overall glycemic control in lean diabetic rodents. Meal-induced profiles of ghrelin, GLP-1, and PYY in GK rats are significantly modified by SG and GB and become similar to those of non-diabetic Wistar rats. Our data do not support the hypothesis that duodenal exclusion and early contact of food with the ileal mucosa alone explain changes in gut hormone profile in GK rats after gastrointestinal surgery.

Insulin resistance and beta cell function before and after sleeve gastrectomy in obese patients with impaired fasting glucose or type 2 diabetes.

BACKGROUND: Pathophysiology of type 2 diabetes (T2D) includes insulin resistance (IR) and insufficient insulin secretion. Remission in obese patients can be achieved through surgically induced weight loss. Sleeve gastrectomy is a novel technique for the treatment of morbid obesity, and its effects on the metabolic syndrome and T2D have not yet been fully understood. METHODS: From February 2008 to July 2010, sleeve gastrectomy as stand-alone treatment for severe or morbid obesity was performed in 23 patients with T2D or impaired fasting glucose (IFG). No postoperative complications occurred and patients were dismissed from hospital on day 2 after surgery. Body mass index (BMI), fasting blood glucose (FBG) and fasting insulin were determined before and up to 24 months after surgery. IR and beta cell function were calculated using the modified homeostasis model assessment (HOMA2). RESULTS: BMI, FBG and fasting insulin improved significantly as early as 3 months after surgery. Threefold increased preoperative insulin resistance (3.05) decreased to near-normal values (1.14) during the same period. Interestingly, overall beta cell function diminished at 12 months of follow-up (79.6 %), in comparison with preoperative values (117.8 %). Patients with a markedly reduced preoperative beta cell function (<40 %) did not achieve a complete remission after surgery. CONCLUSIONS: In obese patients with T2D and IFG, commonly characterized by an augmented beta cell function and an increased insulin resistance, sleeve gastrectomy induces remission through reduction of insulin resistance. Preoperative IR and beta cell function calculated by HOMA2 deserve further studies in patients undergoing metabolic surgery.

Glucagon secretion after metabolic surgery in diabetic rodents.

Excessive or inadequate glucagon secretion promoting hepatic gluconeogenesis and glycogenolysis is believed to contribute to hyperglycemia in patients with type 2 diabetes. Currently, metabolic surgery is an accepted treatment for obese patients with type 2 diabetes and has been shown to improve glycemic control in Goto-Kakizaki (GK) rats, a lean animal model for type 2 diabetes. However, the effects of surgery on glucagon secretion are not yet well established. In this study, we randomly assigned forty 12- to 14-week-old GK rats to four groups: control group (GKC), sham surgery (GKSS), sleeve gastrectomy (GKSG), and gastric bypass (GKGB). Ten age-matched Wistar rats served as a non-diabetic control group (WIC). Glycemic control was assessed before and 4 weeks after surgery. Fasting- and mixed-meal-induced plasma levels of insulin and glucagon were measured. Overall glycemic control improved in GKSG and GKGB rats. Fasting insulin levels in WIC rats were similar to those for GKC or GKSS rats. Fasting glucagon levels were highest in GKGB rats. Whereas WIC, GKC, and GKSS rats showed similar glucagon levels, without any significant meal-induced variation, a significant rise occurred in GKSG and GKGB rats, 30 min after a mixed meal, which was maintained at 60 min. Both GKSG and GKGB rats showed an elevated glucagon:insulin ratio at 60 min in comparison with all other groups. Surprisingly, the augmented post-procedural glucagon secretion was accompanied by an improved overall glucose metabolism in GKSG and GKGB rats. Understanding the role of glucagon in the pathophysiology of type 2 diabetes requires further research.

Dietary restriction improves systemic and muscular oxidative stress in type 2 diabetic Goto-Kakizaki rats

No disponible

Type 2 diabetes is a heterogeneous metabolic disease characterized by insulin resistance and Beta-cell dysfunction leading to hyperglycaemia and dyslipidaemia. Dietary intervention seems to improve some of these cellular complications, namely insulin resistance. Our aim was to evaluate the effects of dietary restriction on systemic and skeletal muscle oxidative stress and insulin resistance in normal Wistar rats and (..) (AU)

Dietary restriction improves systemic and muscular oxidative stress in type 2 diabetic Goto-Kakizaki rats.

Type 2 diabetes is a heterogeneous metabolic disease characterized by insulin resistance and ß-cell dysfunction leading to hyperglycaemia and dyslipidaemia. Dietary intervention seems to improve some of these cellular complications, namely insulin resistance. Our aim was to evaluate the effects of dietary restriction on systemic and skeletal muscle oxidative stress and insulin resistance in normal Wistar rats and Goto-Kakizaki (GK) rats, a non-obese type 2 diabetic animal model. Four-month-old normal and diabetic rats were separated in four groups. One group of each strain was maintained with ad libitum standard diet, and the other group was submitted to a dietary restriction (50% of control animals daily food intake), during 2 months. Metabolic profile, insulin resistance indexes and muscle lipids were determined. Oxidative stress parameters were also measured at systemic and muscle levels: protein carbonyl, 8-hydroxy-2'-deoxyguanosine and free 8-isoprostane. Dietary restriction improved lipid profile in both strains and urinary free 8-isoprostane and plasma carbonyl compounds in diabetic rats. An improvement of muscle triglycerides accumulation and 8-isoprostane concentration and a reduction of insulin resistance were also observed in GK rats. Our data show that dietary restriction ameliorates systemic and skeletal muscle oxidative stress state in type 2 diabetes, which is associated with improved insulin resistance.

Metformin restores endothelial function in aorta of diabetic rats.

BACKGROUND AND PURPOSE: The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been fully elucidated. This study was designed to assess the effect of metformin on impaired endothelial function, oxidative stress, inflammation and advanced glycation end products formation in type 2 diabetes mellitus. EXPERIMENTAL APPROACH: Goto-Kakizaki (GK) rats, an animal model of nonobese type 2 diabetes, fed with normal and high-fat diet during 4 months were treated with metformin for 4 weeks before evaluation. Systemic oxidative stress, endothelial function, insulin resistance, nitric oxide (NO) bioavailability, glycation and vascular oxidative stress were determined in the aortic rings of the different groups. A pro-inflammatory biomarker the chemokine CCL2 (monocyte chemoattractant protein-1) was also evaluated. KEY RESULTS: High-fat fed GK rats with hyperlipidaemia showed increased vascular and systemic oxidative stress and impaired endothelial-dependent vasodilatation. Metformin treatment significantly improved glycation, oxidative stress, CCL2 levels, NO bioavailability and insulin resistance and normalized endothelial function in aorta. CONCLUSION AND IMPLICATIONS: Metformin restores endothelial function and significantly improves NO bioavailability, glycation and oxidative stress in normal and high-fat fed GK rats. This supports the concept of the central role of metformin as a first-line therapeutic to treat diabetic patients in order to protect against endothelial dysfunction associated with type 2 diabetes mellitus.

Insulin and metformin may prevent renal injury in young type 2 diabetic Goto-Kakizaki rats.

Type 2 diabetes is increasing at epidemic proportions throughout the world, and diabetic nephropathy is the principal cause of end stage renal failure. Approximately 40% of patients with type 2 diabetes may progress to nephropathy and a good metabolic control can prevent the development of diabetic renal injury. The aim of our study was to evaluate, in young type 2 diabetic Goto-Kakizaki (GK) rats fed with atherogenic diet, the effects of the anti-diabetic compounds insulin, metformin and gliclazide on renal damage. GK rats fed with atherogenic diet showed increased body weight and fasting blood glucose, total cholesterol, triglycerides, C-reactive protein and protein carbonyl levels and lower HDL-cholesterol concentration; renal markers of inflammation and fibrosis were also elevated. All the anti-diabetic agents ameliorated fasting glycaemia and insulin resistance but only insulin and metformin were able to improve glycoxidation, fibrosis and inflammation kidney parameters. Our data suggest that insulin and metformin treatments, improving glicoxidative, inflammatory and fibrotic renal damage markers, play a key role in the prevention of diabetic nephropathy.

Beneficial effects of dietary restriction in type 2 diabetic rats: the role of adipokines on inflammation and insulin resistance.

Inflammation plays an important role in diabetes mellitus and its complications. In this context, the negative cross-talk between adipose tissue and skeletal muscle leads to disturbances in muscle cell insulin signalling and induces insulin resistance. Because several studies have shown that energy restriction brings some benefits to diabetes, the aim of the present study was to evaluate the effects of dietary restriction on systemic and skeletal muscle inflammatory biomarkers, such C-reactive protein, adipokines and cytokines, and in insulin resistance in Goto-Kakizaki rats. This is an animal model of spontaneous non-obese type 2 diabetes with strongly insulin resistance and without dyslipidaemia. Animals were maintained during 2 months of dietary restriction (50 %) and were killed at 6 months of age. Some biochemical determinations were done using ELISA and Western blot. Data from the present study demonstrate that in Goto-Kakizaki rats the dietary restriction improved insulin resistance, NEFA levels and adipokine profile and ameliorated inflammatory cytokines in skeletal muscle. These results indicate that dietary restriction in type 2 diabetes enhances adipose tissue metabolism leading to an improved skeletal muscle insulin sensitivity.

Endothelial dysfunction in type 2 diabetes: effect of antioxidants.

Individuals with insulin resistance and diabetes mellitus have increased cardiovascular morbidity and mortality, caused in part by vascular complications. Endothelial dysfunction has been implicated in the pathogenesis of vascular diabetic disease. This abnormal function of the vasculature precedes cardiovascular disease and is associated with impaired endothelium-dependent vasorelaxation. The main etiology of the increased mortality and morbidity of type 2 diabetic patients is atherosclerosis. Increased production of free radicals is associated with the pathophysiology of diabetes, resulting in oxidative damage to lipids and proteins. Reduction of oxidative stress in diabetic patients may delay the onset of atherogenesis and the appearance of micro- and macrovascular complications. Alpha-lipoic acid (LA) is a multifunctional antioxidant that has been shown to have beneficial effects on polyneuropathy and on markers of oxidative stress in various tissues. This study was conducted to investigate the effects of LA on endothelial function in diabetic and hyperlipidemic animal models. Carbohydrate and lipid metabolism, endothelial function, plasma malondialdehyde (MDA) and urinary 8-hydroxydeoxyguanosine (8-OHdG) were assessed in non-diabetic controls (Wistar rats), untreated diabetic Goto-Kakizaki (GK) rats and, atherogenic diet (AD)-fed GK rats (fed with atherogenic diet only, treated with alpha-lipoic acid and treated with vehicle, for 3 months). AD resulted in a 3-fold increase in both total and non-HDL serum cholesterol levels and in a 2-fold increase triglyceride levels while endothelial function was significantly reduce MDA and 8-OHdG levels were higher in the GK and GK hyperlipidemic groups and were completely reversed by the antioxidant. Hyperlipidemic GK diabetic rats showed significantly reduced endothelial function that was partially improved with LA. Furthermore, lipoic acid significantly reduced serum cholesterol levels, without lowering HDL cholesterol. Alpha-lipoic acid supplementation represents an achievable adjunct therapy to improve endothelial function and reduce oxidative stress, factors that are implicated in the pathogenesis of atherosclerosis in diabetes.