14-Day Ketone Supplementation Lowers Glucose and Improves Vascular Function in Obesity: A Randomized Crossover Trial.

CONTEXT: Postprandial hyperglycemia increases systemic inflammation and is a risk factor for cardiovascular disease. A ketone monoester (KME) drink containing ß-hydroxybutyrate (ß-OHB) rapidly lowers plasma glucose, which may be a strategy protecting against postprandial hyperglycemia. OBJECTIVE: We hypothesized that KME would attenuate 2-hour postprandial glucose, lower systemic inflammation, and improve vascular function in adults with obesity. METHODS: In a randomized crossover design, 14 participants with obesity (age = 56 ±â€…12 years; body mass index = 32.8 ±â€…7.7 kg/m2) consumed KME (12 g ß-OHB) or placebo 15 minutes prior to each meal for 14 days with all meals provided and matched between conditions. Postprandial glycemia was assessed by continuous glucose monitoring. Vascular function and inflammation were assessed before and after treatment periods. RESULTS: Postprandial glucose was 8.0% lower in KME versus placebo (g = 0.735; P = 0.011) and 24-hour average glucose reduced by 7.8% (g = 0.686; P = 0.0001). Brachial artery flow-mediated dilation increased from 6.2  ±â€… 1.5% to 8.9 ±â€…3.3% in KME (g = 1.05; P = 0.0004) with no changes in placebo (condition × time interaction, P = 0.004). There were no changes in plasma cytokines; however, lipopolysaccharide-stimulated monocyte caspase-1 activation was lower following KME supplementation versus placebo (stimulation × condition × time interaction; P = 0.004). The KME supplement was well tolerated by participants and adherence to the supplementation regimen was very high. CONCLUSIONS: In adults with obesity, 14 days of premeal KME supplementation improves glucose control, enhances vascular function, and may reduce cellular inflammation. KME supplementation may be a viable, nonpharmacological approach to improving and protecting vascular health in people with heightened cardiometabolic risk.

Herbal formula LLKL ameliorates hyperglycaemia, modulates the gut microbiota and regulates the gut-liver axis in Zucker diabetic fatty rats.

LLKL, a new traditional Chinese medicine formula containing Edgeworthia gardneri (Wall.) Meisn., Sibiraea angustata and Crocus sativus L. (saffron), was designed to ameliorate type 2 diabetes mellitus. Despite the therapeutic benefits of LLKL, its underlying mechanisms remain elusive. This study evaluated the LLKL anti-diabetic efficacy and its effect on gut microbiota to elucidate its mechanism of action in Zucker diabetic fatty rats. We found that administration of different LLKL concentrations (4.68, 2.34 and 1.17 g/kg/d) improved several diabetic parameters after a 6-week treatment. Moreover, LLKL modulated gut microbiota dysbiosis, increased the expression of occluding and maintained intestinal epithelial homeostasis, leading to a reduction in LPS, TNF-α and IL-6 levels. Hepatic transcriptomic analysis showed that the Toll-like receptor signalling pathway was markedly enriched by LLKL treatment. RT-qPCR results validated that LLKL treatment decreased the expressions of TLR4, MyD88 and CTSK. Furthermore, a gene set enrichment analysis indicated that LLKL enhanced the insulin signalling pathway and inhibited glycerolipid metabolism and fatty acid metabolism, which were verified by the liver biochemical analysis. These findings demonstrate that LLKL ameliorates hyperglycaemia, modulates the gut microbiota and regulates the gut-liver axis, which might contribute to its anti-diabetic effect.

Isoliquiritigenin attenuates diabetic cardiomyopathy via inhibition of hyperglycemia-induced inflammatory response and oxidative stress.

BACKGROUND: Inflammation and oxidative stress play essential roles in the occurrence and progression of diabetic cardiomyopathy (DCM). Isoliquiritigenin (ISL), a natural chalcone, exhibits strong anti-inflammatory and antioxidant activities. HYPOTHESIS/PURPOSE: In this study, we aimed to investigate the protective effects of ISL on DCM using high glucose (HG)-challenged cultured cardiomyocytes and streptozotocin (STZ)-induced diabetic mice. STUDY DESIGN AND METHODS: Embryonic rat heart-derived H9c2 cells challenged with a high concentration of glucose were used to evaluate the anti-inflammatory and antioxidant effects of ISL. STZ-induced diabetic mice were used to study the effects of ISL in DCM in vivo. Furthermore, cardiac fibrosis, hypertrophy, and apoptosis were explored both in vitro and in vivo. RESULTS: ISL effectively inhibited HG-induced hypertrophy, fibrosis, and apoptosis probably by alleviating the inflammatory response and oxidative stress in H9c2 cells. Results from in vivo experiments showed that ISL exhibited anti-inflammatory and antioxidant stress activities that were characterized by the attenuation of cardiac hypertrophy, fibrosis, and apoptosis, which resulted in the maintenance of cardiac function. The protective effects of ISL against inflammation and oxidative stress were mediated by the inhibition of mitogen-activated protein kinases (MAPKs) and induction of nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway, respectively. CONCLUSION: Our results provided compelling evidence that ISL, by virtue of neutralizing excessive inflammatory response and oxidative stress, could be a promising agent in the treatment of DCM. Targeting the MAPKs and Nrf2 signaling pathway might be an effective therapeutic strategy for the prevention and treatment of DCM.

Physalis alkekengi L. Extract Reduces the Oxidative Stress, Inflammation and Apoptosis in Endothelial Vascular Cells Exposed to Hyperglycemia.

To find new natural remedies in diabetes, this study investigated the biological activity of two extracts obtained from the fruits (PhyF) and herba (PhyH) of Physalis alkekengi var. franchetii L. on human umbilical vein endothelial cells (HUVECs) exposed to normo- and hyperglycemic conditions. The biological effect was quantified by malondialdehyde, IL-31 and IL-33 levels in correlation with physico-chemical characterization and antioxidant activity. Additionally, from PhyP extract, the caspase-3, IL-6, IL-10, tumor necrosis factor (TNF)-α and nuclear transcription factor NFkB expressions were evaluated. HPLC analysis revealed a significant number of phenolic compounds, especially in PhyF extract, with a good antioxidant activity as highlighted by TEAC, CUPRAC or DPPH methods. On HUVECS cells, the extracts were not toxic even at high concentrations. Particularly PhyF extract, diminished lipid peroxidation and inhibited the IL-31 and IL-33 secretions induced by hyperglycemia. The inhibitory effect on proinflammatory cytokines was noticed after both doses of PhyF extract in parallel with the upregulation of anti-inflammatory cytokine IL-10. Moreover, PhyF, especially in a low dose, reduced caspase-3 active form. These experimental findings suggest that Physalis fruits extract exerted beneficial effects in hyperglycemia by inhibition of oxidative stress, inflammation and apoptosis being a good adjuvant option in diabetes.

The Powdered Root of Eurycoma longifolia Jack Improves Beta-Cell Number and Pancreatic Islet Performance through PDX1 Induction and Shows Antihyperglycemic Activity in db/db Mice.

Non-insulin-dependent diabetes mellitus (NIDDM) is a common metabolic disorder worldwide. In addition to the chief feature of long-standing hyperglycemia, dyslipidemia, hyperinsulinemia, and a number of complications develop in parallel. It is believed that an adequate control of blood glucose levels can cause these complications to go into remission. This study was performed to evaluate the antidiabetic activity of Eurycoma longifolia Jack (EL) in vivo. The blood-glucose-lowering activity of EL was studied in db/db mice administered crude powdered EL root (25, 50, and 100 mg/kg) orally for eight weeks. At the end of the study, HbA1c, insulin, plasma lipid levels, and histopathology were performed. Powdered EL root showed significant antihyperglycemic activity along with the control of body weight. After eight weeks of treatment, both the blood cholesterol level and the glycogen deposit in hepatocytes were remarkably lower, whereas the secreting insulin level was elevated. An improvement in islet performance was manifested as an increase in beta-cell number and pancreatic and duodenal homeobox 1 (PDX1) expression. Neogenesis or formation of new islets from pancreatic duct epithelial cells seen in the EL-treated group was encouraging. This study confirms the antihyperglycemic activity of EL through PDX1-associated beta-cell expansion resulting in an enhancement of islet performance.

Allithiamine Alleviates Hyperglycaemia-Induced Endothelial Dysfunction.

Diabetes mellitus-related morbidity and mortality is a rapidly growing healthcare problem, globally. Several nutraceuticals exhibit potency to target the pathogenesis of diabetes mellitus. The antidiabetic effects of compounds of garlic have been extensively studied, however, limited data are available on the biological effects of a certain garlic component, allithiamine. In this study, allithiamine was tested using human umbilical cord vein endothelial cells (HUVECs) as a hyperglycaemic model. HUVECs were isolated by enzymatic digestion and characterized by flow cytometric analysis using antibodies against specific marker proteins including CD31, CD45, CD54, and CD106. The non-cytotoxic concentration of allithiamine was determined based on MTT, apoptosis, and necrosis assays. Subsequently, cells were divided into three groups: incubating with M199 medium as the control; or with 30 mMol/L glucose; or with 30 mMol/L glucose plus allithiamine. The effect of allithiamine on the levels of advanced glycation end-products (AGEs), activation of NF-κB, release of pro-inflammatory cytokines including IL-6, IL-8, and TNF-α, and H2O2-induced oxidative stress was investigated. We found that in the hyperglycaemia-induced increase in the level of AGEs, pro-inflammatory changes were significantly suppressed by allithiamine. However, allithiamine could not enhance the activity of transketolase, but it exerts a potent antioxidant effect. Collectively, our data suggest that allithiamine could alleviate the hyperglycaemia-induced endothelial dysfunction due to its potent antioxidant and anti-inflammatory effect by a mechanism unrelated to the transketolase activity.

Protective Effects of Antioxidant Polyphenols against Hyperglycemia-Mediated Alterations in Cerebral Endothelial Cells and a Mouse Stroke Model.

SCOPE: Hyperglycemia alters cerebral endothelial cell and blood-brain barrier functions, aggravating cerebrovascular complications such as stroke during diabetes. Redox and inflammatory changes play a causal role. This study evaluates polyphenol protective effects in cerebral endothelial cells and a mouse stroke model during hyperglycemia. METHODS AND RESULTS: Murine bEnd.3 cerebral endothelial cells and a mouse stroke model are exposed to a characterized, polyphenol-rich extract of Antirhea borbonica or its predominant constituent caffeic acid, during hyperglycemia. Polyphenol effects on redox, inflammatory and vasoactive markers, infarct volume, and hemorrhagic transformation are determined. In vitro, polyphenols improve reactive oxygen species levels, Cu/Zn superoxide dismutase activity, and both NAPDH oxidase 4 and nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression deregulated by high glucose. Polyphenols reduce Nrf2 nuclear translocation and counteract nuclear factor-ĸappa B activation, interleukin-6 secretion, and the altered production of vasoactive markers mediated by high glucose. In vivo, polyphenols reduce cerebral infarct volume and hemorrhagic transformation aggravated by hyperglycemia. Polyphenols attenuate redox changes, increase vascular endothelial-Cadherin production, and decrease neuro-inflammation in the infarcted hemisphere. CONCLUSION: Polyphenols protect against hyperglycemia-mediated alterations in cerebral endothelial cells and a mouse stroke model. It is relevant to assess polyphenol benefits to improve cerebrovascular damages during diabetes.

Postprandial Hyperglycemia Stimulates Neuroglial Plasticity in Hypothalamic POMC Neurons after a Balanced Meal.

Mechanistic studies in rodents evidenced synaptic remodeling in neuronal circuits that control food intake. However, the physiological relevance of this process is not well defined. Here, we show that the firing activity of anorexigenic POMC neurons located in the hypothalamus is increased after a standard meal. Postprandial hyperactivity of POMC neurons relies on synaptic plasticity that engages pre-synaptic mechanisms, which does not involve structural remodeling of synapses but retraction of glial coverage. These functional and morphological neuroglial changes are triggered by postprandial hyperglycemia. Chemogenetically induced glial retraction on POMC neurons is sufficient to increase POMC activity and modify meal patterns. These findings indicate that synaptic plasticity within the melanocortin system happens at the timescale of meals and likely contributes to short-term control of food intake. Interestingly, these effects are lost with a high-fat meal, suggesting that neuroglial plasticity of POMC neurons is involved in the satietogenic properties of foods.

Inhibition of GLUT2 transporter by geraniol from Cymbopogon martinii: a novel treatment for diabetes mellitus in streptozotocin-induced diabetic rats.

OBJECTIVE: To isolate and identify the bioactive component from Cymbopogon martinii having GLUT2 transporter inhibitory activity - towards development of a novel strategy for treatment of diabetes mellitus. METHOD: Isolation of bioactive component was carried out using differential solvent extraction, HPTLC and HPLC, and identification was done by GC-MS. In-vitro studies on intestine, liver, kidney and in-vivo assessment by OGTT and long-term treatment on diabetic rats were carried out. KEY FINDINGS: Geraniol was isolated and identified as bioactive component. Intestinal glucose absorption demonstrated 60.28% inhibition of transport at 648.34 µm of geraniol. It was found to inhibit glucose release from liver on adrenaline challenge by 89.82% at 324.17 µm/ml. Kidney glycogen content doubled using 648.34 µm of geraniol as compared to control. Geraniol demonstrated 2.14 times higher renal glucose output than diabetic control. OGTT demonstrated prevention of postprandial spikes. Prolonged treatment for 60 days with 29.37 mm/kg B.W. twice a day of geraniol improved the lipid profile, HbA1C levels and renal parameters. In mRNA studies for 10 days, over expression of GLUT2 was prevented by geraniol. CONCLUSIONS: Inhibition of GLUT2 by geraniol has the potential to reduce hyperglycaemia and prevent secondary complications in diabetes.

Sheng Mai San protects H9C2 cells against hyperglycemia-induced apoptosis.

BACKGROUND: Sheng Mai San (SMS) has been proven to exhibit cardio-protective effects. This study aimed to explore the molecular mechanisms of SMS on hyperglycaemia (HG)-induced apoptosis in H9C2 cells. METHODS: HG-induced H9C2 cells were established as the experimental model, and then treated with SMS at 25, 50, and 100 µg/mL. H9C2 cell viability and apoptosis were quantified using MTT and Annexin V-FITC assays, respectively. Furthermore, Bcl-2/Bax signalling pathway protein expression and Fas and FasL gene expression levels were quantified using western blotting and RT-PCR, respectively. RESULTS: SMS treatments at 25, 50, 100 µg/mL significantly improved H9C2 cell viability and inhibited H9C2 cell apoptosis (p < 0.05). Compared to the HG group, SMS treatment at 25, 50, and 100 µg/mL significantly downregulated p53 and Bax expression and upregulated Bcl-2 expression (p < 0.05). Moreover, SMS treatment at 100 µg/mL significantly downregulated Fas and FasL expression level (p < 0.05) when compared to the HG group. CONCLUSION: SMS protects H9C2 cells from HG-induced apoptosis probably by downregulating p53 expression and upregulating the Bcl-2/Bax ratio. It may also be associated with the inhibition of the Fas/FasL signalling pathway.

Management of people with Type 2 diabetes shared between a specialized outpatient clinic and primary health care is noninferior to management in a specialized outpatient clinic: a randomized, noninferiority trial.

AIM: To evaluate whether management of people with Type 2 diabetes shared between a specialized outpatient clinic and primary health care has noninferior HbA1c outcomes compared with mono-sectorial management in a specialized outpatient clinic. METHODS: A randomized controlled, noninferiority study. People with moderate hyperglycaemia, hypertension and/or incipient complications were eligible for the study. All participants had annual comprehensive check-ups at the outpatient clinic. Quarterly check-ups were conducted by general practitioners (GPs) for the shared care group and by endocrinologists at the outpatient clinic for the control group. The primary outcome was the mean difference in HbA1c from baseline to 12 months of follow-up. The noninferiority margin for HbA1c was 4.4 mmol/mol. RESULTS: A total of 140 people were randomized [age 65.0 ± 0.9 years, HbA1c 52 ± 0.8 mmol/mol (6.9 ± 0.1%), systolic BP 135.6 ± 1.1 mmHg; all mean ± sem]. Peripheral neuropathy was present in 68% of participants and microalbuminuria in 19%; 15% had history of a previous major cardiovascular event. Among study completers (n = 133), HbA1c increased by 2.3 mmol/mol (0.2%) in the shared care group and by 1.0 mmol/mol (0.1%) in the control group, with a between-group difference of 1.3 mmol/mol [90% confidence interval (CI) -1.3, 3.9] (0.1%, 90% CI -0.1, 0.4). Noninferiority was confirmed in both per protocol and intention to treat analyses. CONCLUSION: We found that our shared care programme was noninferior to specialized outpatient management in maintaining glycaemic control in this group of people with Type 2 diabetes. Shared care should be considered for the future diabetes management of Type 2 diabetes.

Sweet fish: Fish models for the study of hyperglycemia and diabetes.

Fish are good for your health in more ways than you may expect. For one, eating fish is a common dietary recommendation for a healthy diet. However, fish have much more to provide than omega-3 fatty acids to your circulatory system. Some fish species now serve as important and innovative model systems for diabetes research, providing novel and unique advantages compared with classical research models. Not surprisingly, the largest share of diabetes research in fish occurs in the laboratory workhorse among fish, the zebrafish (Danio rerio). Established as a genetic model system to study development, these small cyprinid fish have eventually conquered almost every scientific discipline and, over the past decade, have emerged as an important model system for metabolic diseases, including diabetes mellitus. In this review we highlight the practicability of using zebrafish to study diabetes and hyperglycemia, and summarize some of the recent research and breakthroughs made using this model. Equally exciting is the appearance of another emerging discipline, one that is taking advantage of evolution by studying cases of naturally occurring insulin resistance in fish species. We briefly discuss two such models in this review, namely the rainbow trout (Oncorhynchus mykiss) and the cavefish (Astyanax mexicanus).

Tocotrienol-rich fraction supplementation reduces hyperglycemia-induced skeletal muscle damage through regulation of insulin signaling and oxidative stress in type 2 diabetic mice.

Chronic hyperglycemia induces impairment of muscle growth and development of diabetes mellitus (DM). Since skeletal muscle is the major site for disposal of ingested glucose, impaired glucose metabolism causes imbalance between protein synthesis and degradation which adversely affects physical mobility. In this study, we investigated the effect of tocotrienol-rich fraction (TRF) supplementation on skeletal muscle damage in diabetic mice. Diabetes was induced by a high-fat diet with streptozotocin (STZ) injection (100 mg/kg) in male C57BL/6J mice. After diabetes was induced (fasting blood glucose levels≥250 mg/dl), normal control (CON) and diabetic control (DMC) groups were administrated with olive oil, while TRF treatment groups were administrated with TRF (dissolved in olive oil) at low dose (100 mg/kg BW, LT) or high dose (300 mg/kg BW, HT) by oral gavage for 12 weeks. TRF supplementation ameliorated muscle atrophy, plasma insulin concentration and homeostatic model assessment estimated insulin resistance in diabetic mice. Moreover, TRF treatment up-regulated IRS-1 and Akt levels accompanied by increased translocation of GLUT4. Furthermore, TRF increased mitochondrial biogenesis by activating SIRT1, SIRT3 and AMPK in diabetic skeletal muscle. These changes were in part mechanistically explained by reduced levels of skeletal muscle proteins related to oxidative stress (4-hydroxynonenal, protein carbonyls, Nrf2 and HO-1), inflammation (NFkB, MCP-1, IL-6 and TNF-α), and apoptosis (Bax, Bcl2 and caspase-3) in diabetic mice. Taken together, these results suggest that TRF might be useful as a beneficial nutraceutical to prevent skeletal muscle atrophy associated with diabetes by regulating insulin signaling via AMPK/SIRT1/PGC1α pathways in type 2 diabetic mice.

Quercetin Prevents Diastolic Dysfunction Induced by a High-Cholesterol Diet: Role of Oxidative Stress and Bioenergetics in Hyperglycemic Rats.

Alterations in cardiac energy metabolism play a key role in the pathogenesis of diabetic cardiomyopathy. Hypercholesterolemia associated with bioenergetic impairment and oxidative stress has not been well characterized in the cardiac function under glycemic control deficiency conditions. This work aimed to determine the cardioprotective effects of quercetin (QUE) against the damage induced by a high-cholesterol (HC) diet in hyperglycemic rats, addressing intracellular antioxidant mechanisms and bioenergetics. Quercetin reduced HC-induced alterations in the lipid profile and glycemia in rats. In addition, QUE attenuated cardiac diastolic dysfunction (increased E:A ratio), prevented cardiac cholesterol accumulation, and reduced the increase in HC-induced myocyte density. Moreover, QUE reduced HC-induced oxidative stress by preventing the decrease in GSH/GSSG ratio, Nrf2 nuclear translocation, HO-1 expression, and antioxidant enzymatic activity. Quercetin also counteracted HC-induced bioenergetic impairment, preventing a reduction in ATP levels and alterations in PGC-1α, UCP2, and PPARγ expression. In conclusion, the mechanisms that support the cardioprotective effect of QUE in rats with HC might be mediated by the upregulation of antioxidant mechanisms and improved bioenergetics on the heart. Targeting bioenergetics with QUE can be used as a pharmacological approach to modulate structural and functional changes of the heart under hypercholesterolemic and hyperglycemic conditions.

Protective effect of mulberry fruit anthocyanin on human hepatocyte cells (LO2) and Caenorhabditis elegans under hyperglycemic conditions.

Type 2 diabetes is a chronic disease and hyperglycemia is important in the pathogenesis of diabetic complications. Exposure of LO2 cells to high glucose resulted in cellular glucose consumption and uptake decreases, reactive oxygen species (ROS) and superoxide anion (O2-) accumulation and mitochondrial dysfunction, which could be partly recovered by mulberry anthocyanin extract (MAE). And these protective effects were partly associated with regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets. As the insulin-signaling pathway is evolutionarily well conserved from Caenorhabditis elegans to mammals, C. elegans has been considered as a model system to study effects of glucose toxicity. Glucose shortened the lifespan of C. elegans, while MAE suppressed the damage, accompanied by malondialdehyde (MDA) and triglyceride accumulation reduction as well as total superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity recovery and PMK-1/p38 expression promotion. In contrast, MAE failed to recover shortened longevity, glucose and triglyceride accumulation in daf-2 (-) mutants fed a glucose-supplemented diet. Transcriptional profile revealed MAE intervention led to 92 genes alteration compared with the glucose-treatment. Interestingly, expressions of DAF-2/insulin receptor related genes were increased by glucose but impaired by MAE in nematodes. Our studies suggested that MAE might help to improve the antioxidant defense system, resulting in prevention of glucose-induced damage both in vitro and in vivo.

Marked recovery from glucotoxicity of ß-cell function after medical nutrition therapy without pharmacotherapy in type 2 diabetic outpatients with extreme hyperglycemia: a pilot retrospective study.

We investigated whether glucotoxicity of ß-cell function could be eliminated after medical nutrition therapy (MNT) without forced correction of hyperglycemia by anti-diabetic medications including exogenous insulin administration. We analyzed newly diagnosed type 2 diabetic outpatients with hemoglobin A1c (HbA1c) of 10.1 ± 1.5%, who were treated by MNT at least for three months, without any aid of anti-diabetic medications. The ß-cell function was calculated as the product of the ΔIns0-120/ΔGlu0-120 and the Matsuda index, where ΔIns0-120/ΔGlu0-120 represents the ratio of the incremental concentrations of insulin to those of glucose during the 0- to 120-min time periods under a 75-g oral glucose tolerance test. After MNT, HbA1c levels were reduced to 7.0 ± 1.0% (p < 0.001). The ß-cell function was significantly improved (n = 13; p = 0.001; effect size d = 1.9). Fasting plasma glucose became below 7.0 mmol/l in 57% (8/13), and 120-minute plasma glucose became below 11.1 mmol/l in 43% (6/13). The ß-cell function after MNT was significantly correlated with HbA1c levels achieved after MNT (Pearson's correlation coefficient r = -0.62, p = 0.025). In conclusion, the ß-cell dysfunction was ameliorated after MNT without glucose-lowering pharmacotherapy in newly diagnosed type 2 diabetic outpatients who presented extreme hyperglycemia.

Grape powder consumption affects the expression of neurodegeneration-related brain proteins in rats chronically fed a high-fructose-high-fat diet.

Abnormal glucose metabolism in the brain is recognized to be associated with cognitive decline. Because grapes are rich in polyphenols that produce antioxidative and blood sugar-lowering effects, we investigated how grape consumption affects the expression and/or phosphorylation of neurodegeneration-related brain proteins in aged rats fed a high-fructose-high-fat (HFHF) diet. Wistar rats were maintained on the HFHF diet from the age of 8 weeks to 66 weeks, and then on an HFHF diet containing either 3% or 6% grape powder as an intervention for 12 weeks. Western blotting was performed to measure the expression/phosphorylation levels of several cortical and hippocampal proteins, including amyloid precursor protein (APP), tau, phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase (ERK), receptor for advanced glycation end products (RAGEs), erythroid 2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF). Inclusion of up to 6% grape powder in the diet markedly reduced RAGE expression and tau hyperphosphorylation, but upregulated the expression of Nrf2 and BDNF, as well as the phosphorylation of PI3K and ERK, in the brain tissues of aged rats fed the HFHF diet. Thus, grape powder consumption produced beneficial effects in HFHF-diet-fed rats, exhibiting the potential to ameliorate changes in neurodegeneration-related proteins in the brain.

Zinc's role in the glycemic control of patients with type 2 diabetes: a systematic review.

Past research has shown the importance of zinc in several metabolic processes, such as the glucidic metabolism. The present systematic review aims to discuss zinc's participation in the glycemic control of type 2 diabetes mellitus (DM2) patients. In order to accomplish that, a systematic search was performed in the Pubmed database using the following indexed and theme-related descriptors: "zinc" AND "type 2 diabetes mellitus", AND MeSH terms related to glycemic control combined with the boolean operator OR. In total, 1078 articles were retrieved from the research, of which 15 articles of original studies conducted with DM2 patients were included, with three being about the effect of mineral supplementation and 12 reporting observational studies. The main findings of these studies consisted of low body contents of zinc and high excretion of zinc in urine. Hyperglycemia was one of the mechanisms that caused these alterations owing to its interference in zinc reabsorption via renal cells. Another evidence was the negative correlation between the glycated hemoglobin percentage (%HbA1c) and the plasma zinc levels. Additionally, it has been observed that zinc supplementation in DM2 patients has improved glycemic control, since the %HbA1c significantly reduced in these individuals. This present review shows the positive effect of adequate zinc levels on glycemic control, whether it is through dietetic ingestion or supplementation, since its role in insulin homeostasis is clear.

Association between clinical condition and F-waves changes in the acute phase of stroke.

OBJECTIVE: To relate F-waves with clinical and laboratory exams in the acute phase of stroke. METHODS: Inclusion criteria for this cross-sectional study were: hemiplegia, absence of previous cranial trauma, myopathy, diabetes, alcoholism or other known causes of peripheral neuropathy, and normal sensory and motor conduction. The National Institutes of Health Stroke Scale (NIHSS) score, glycemia, glucosilate hemoglobin, and CPK were obtained at admission by routine blood exams. After hospital admission, the F-wave latencies and persistence were obtained from the deep peroneal nerve using symmetrical techniques. RESULTS: Evaluation of 20 individuals - mean age 66 years, 50% male and 85% Caucasian - showed association of F-wave persistence with glycemia (r = 0.71; p < 0.001) and NIHSS categorized (NIHSS 1-7 = 65.0 x NIHSS 9-23 = 100; p = 0.004). Multivariate analysis found only association of F-wave persistence with glycemia ß = 0.59 (0.44-0.74); p < 0.001. CONCLUSION: The increase in the persistence of F-waves are associated with hyperglycemia in the acute phase of stroke.

Association between clinical condition and F-waves changes in the acute phase of stroke / Associação entre condição clínica e alterações das ondas-F na fase aguda do acidente vascular cerebral

ABSTRACT Objective To relate F-waves with clinical and laboratory exams in the acute phase of stroke. Methods Inclusion criteria for this cross-sectional study were: hemiplegia, absence of previous cranial trauma, myopathy, diabetes, alcoholism or other known causes of peripheral neuropathy, and normal sensory and motor conduction. The National Institutes of Health Stroke Scale (NIHSS) score, glycemia, glucosilate hemoglobin, and CPK were obtained at admission by routine blood exams. After hospital admission, the F-wave latencies and persistence were obtained from the deep peroneal nerve using symmetrical techniques. Results Evaluation of 20 individuals – mean age 66 years, 50% male and 85% Caucasian – showed association of F-wave persistence with glycemia (r = 0.71; p < 0.001) and NIHSS categorized (NIHSS 1-7 = 65.0 x NIHSS 9-23 = 100; p = 0.004). Multivariate analysis found only association of F-wave persistence with glycemia β = 0.59 (0.44–0.74); p < 0.001. Conclusion The increase in the persistence of F-waves are associated with hyperglycemia in the acute phase of stroke.

RESUMO Objetivo Relacionar as ondas-F com exames clínicos e laboratoriais na fase aguda do acidente vascular cerebral (AVC). Os critérios de inclusão para este estudo transversal foram: hemiplegia, ausência de trauma craniano, miopatia, diabetes, alcoolismo ou outra causa conhecida de neuropatia periférica, além de condução sensorial e motora normal. O National Institutes of Health Stroke Scale (NIHSS), glicemia, hemoglobina glicada e CPK foram obtidos na admissão por meio de exames de rotina. Após a admissão hospitalar, a latência e persistência das ondas-F foram obtidas por meio da estimulação do nervo fibular profundo utilizando técnicas simétricas. Foram avaliados 20 indivíduos – média de idade 66 anos, 50% homem e 85% caucasianos – apresentaram associação univariada da persistência das ondas-F com glicemia (r = 0.71; p < 0.001) e NIHSS categorizado (NIHSS 1–7 = 65.0 x NIHSS 9-23 = 100; p = 0.004). Na regressão multivariada foi encontrado associação somente entre persistência de ondas-F com glicemia β = 0.59(0.44–0.74); p < 0.001. Conclusão O aumento da persistência de ondas-F está associado com maior nível de glicemia na fase aguda do AVC.