Decreased Serum Insulin Concentrations Research Articles

237 Disrupted insulin signaling due to an acute immune response in swine

Abstract Insulin is an anabolic hormone involved in glucose uptake and synthesis of fats, proteins, and glycogen. Altered insulin signaling can occur due to metabolic state, pathogen exposure, and autoimmune disorders. Lipopolysaccharide (LPS), an endotoxin secreted produced by gram-negative bacteria, can induce a severe, systemic immune response. In pigs, chronic LPS exposure has induced insulin resistance. However, the effects of acute exposure to LPS on insulin signaling and resistance have not been elucidated. Crossbred nursery pigs [n = 58, initial body weight (BW) = 12.1 kg ± 0.23 kg] were randomly assigned into two experimental subsets, where 10 animals were designated for repeated blood sampling and 48 animals underwent timed euthanasia for tissue collection. For repeated blood sampling, jugular catheters were placed under anesthesia and the animals were given 48 h to recover before being randomly assigned to treatments. These treatments were an intraperitoneal injection of either 15µg/kg BW LPS or an equal volume of 0.9% Saline (n = 5 pigs/treatment). Blood was collected for 48 h followed by euthanasia. The other 48 pigs were randomly assigned to the same treatments, and then randomly assigned to euthanasia timepoints of 0, 3, 6, 12, 24 or 48 h post injection for tissue collection. Among the catheterized pigs, 2-h post LPS challenge there was a decrease in serum insulin concentration (P < 0.05) and mild hyperglycemia (P < 0.05) post challenge. At 12- and 24-h post LPS challenge there was a decrease in insulin (P < 0.05) and a trend hyperglycemia was also apparent at 24 h (P = 0.063). In liver tissue, insulin related genes exhibited alterations post LPS injection. Phosphoinositide 3-kinase (pi3k) and insulin receptor substrate 1 (irs1) expression were decreased at 3 and 6 h (p< 0.05) and protein kinase b (akt) expression were decreased at 3 h (P < 0.05) post challenge. The expression of insulin inhibitor growth factor receptor bound protein 10 (grb10) was decreased at 6-, 12-, and 24-h after challenge (P < 0.05). Fructose-1-6-bisphosphatase (f16bp) expression was reduced at 3-, 6-, and 12-h (P < 0.05) in the liver while phosphoenolpyruvate carboxykinase (pepck) expression was decreased at 3- and 6-h (P < 0.01) post challenge. Other metabolic genes were decreased at 3-, 6-, and 12-h post LPS challenge, including fatty acid synthase (fas; P < 0.05), carbohydrate response element binding protein (chrebp; P < 0.05), and acetyl CoA carboxylase (acc; P < 0.05). Protein abundance of Akt 3 h after LPS injection was decreased in the liver (P < 0.05). In skeletal muscle 6 h post LPS injection, insulin receptor (insr), insulin-like growth factor receptor (igfr) and fas were all increased (P < 0.05) These results indicate disrupted insulin signaling at various levels after an acute immune response.

Effect of Resistance Training on Adipose Tissue and Serum METRNL Levels in Sucrose Solution Fed Rats

Background: Meteorin-like protein (METRNL) is a novel adipomyokine that may improve glucose tolerance, and its circulating levels are affected by changes in body weight. Objectives: This study aimed to evaluate the effects of eight weeks of resistance training (RT) and high sucrose consumption on serum and adipose tissue METRNL levels in male rats. Methods: In this study, 32 Wistar male rats were divided into normal diet and high sucrose diet groups. After 4 weeks, each group was divided into control and training groups. The rats in the training group were subjected to the RT program (3 days/week, for 8 weeks). In addition to serum and adipose tissue levels of METRNL, we measured epididymal and mesenteric fat mass, serum glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR). Results: High sucrose diet increased fat weights and serum levels of glucose, insulin, and IR index; nevertheless, it reduced the serum levels of METRNL. RT decreased serum insulin concentrations and HOMA-IR. The result of two-way ANOVA and the t-test showed that eight weeks of RT decreased serum levels of METRNL, insulin, and HOMA-IR in sugar solution-fed rats. Conclusions: The results suggest that RT may be an effective intervention to reduce serum METRNL and HOMA-IR levels, which is associated with improving body composition.

Combinatorial treatment of mupirocin nanomicelle in insulin-based gel for wound healing in diabetic rats

Abstract Background: Diabetic wounds remain an important clinical challenge over the past few decades. Nanodrug delivery systems play a crucial role in the treatment of chronic infections and wound healing. Objectives: To evaluate the wound healing potential of newly synthesized and characterized mupirocin (MP) nanomicelle (NM) in insulin (I)-based gel (MP-NM-I), utilizing alloxan-induced diabetic rat model. Materials and Methods: MP-NM-I was prepared by solvent evaporation technique, 96 male rats were assigned randomly into eight groups (n = 12): one group is healthy, and the remaining seven groups were diabetic and wounded receiving treatments of gel base, tween 80, I, MP, MP-I, MP-NM, and MP-NM-I, respectively. Rats were sacrificed after 7 and 14 days of wounding. Blood samples were collected for glucose and insulin concentration measurement. Skin biopsies were examined by histological and immunohistochemical analyses. Results: Diabetes was confirmed after a significant increase in blood glucose and a decrease in serum insulin concentrations (P ≤ 0.001). MP-NM– and MP-NM-I–treated groups presented a rapid wound closure (100 ± 0, P ≤ 0.001), and the bacterial growth in these samples was relatively low (P ≤ 0.001). Histological examination established a significant decrease in inflammatory cells (P ≤ 0.001) with a significant elevation in tissue re-epithelialization, fibroblasts, angiogenesis, and collagen fibers (P ≤ 0.001). Immunohistochemical investigation presented a significant decrease in tumor necrosis factor-α, increase in vascular endothelial growth factors, and interleukin-10 scores (P ≤ 0.001). Conclusion: The developed formula of MP-NM with or without insulin is more effective than MP alone for diabetic wound healing in rats, because it accelerated wound closure. Accordingly, the formula might serve as an innovative tool for diabetic wound healing.

Associations among serum insulin, calprotectin, and C-reactive protein concentrations in Miniature Schnauzers with idiopathic hyperlipidemia before and after feeding an ultra-low-fat diet.

BackgroundMiniature Schnauzers (MS) commonly have idiopathic hypertriglyceridemia (HTGL), which is associated with insulin resistance (IR) and a subclinical inflammatory phenotype.ObjectivesDetermine the association between indicators of IR and inflammatory biomarkers in MS with and without HTGL and identify how indicators of IR are affected by dietary intervention in MS with HTGL.AnimalsSeventy MS with HTGL and 79 MS without HTGL. In addition, 15 MS with HTGL were placed on a low‐fat diet.MethodsSerum concentrations of triglycerides, cholesterol, calprotectin, insulin, and glucose were compared between groups.ResultsSerum glucose and calprotectin concentrations (shown to be higher in MS with HTGL than in MS without HTGL) were inversely correlated (ρ = −.28; P < .001). After dietary intervention, median serum insulin concentrations were 8.1 mU/L compared to 20.8 mU/L before dietary intervention (P = .06). Dogs with complete resolution of HTGL after dietary intervention (5 dogs) had significantly lower serum insulin concentrations compared to baseline (P = .03).Conclusion and Clinical ImportanceThe subclinical inflammatory phenotype in MS with HTGL appears to be associated with IR. Resolution of HTGL by dietary intervention is associated with a decrease in serum insulin concentrations. The implication of the increase in serum calprotectin concentrations after resolution of HTGL warrants further study.

Pemafibrate, a PPAR alpha agonist, attenuates neointima formation after vascular injury in mice fed normal chow and a high-fat diet

Recently, the prevention of cardiovascular events has become one of the most important aims of diabetes care. Peroxisome proliferator-activated receptor (PPAR) agonists have been reported to have vascular protective effects. Here, we examined whether pemafibrate, a selective PPAR alpha agonist, attenuated neointima formation after vascular injury and vascular smooth muscle cell (VSMC) proliferation. We performed endothelial denudation injury in mice treated with a high-fat diet (HFD) or normal chow. Orally administered pemafibrate significantly attenuated neointima formation after vascular injury in HFD and normal chow mice. Interestingly, pemafibrate increased the serum fibroblast growth factor 21 concentration and decreased serum insulin concentrations in HFD mice. In addition, body weight was slightly but significantly decreased by pemafibrate in HFD mice. Pemafibrate, but not bezafibrate, attenuated VSMC proliferation in vitro. The knockdown of PPAR alpha abolished the anti-VSMC proliferation effect of pemafibrate. BrdU assay results revealed that pemafibrate dose-dependently inhibited DNA synthesis in VSMCs. Flow cytometry analysis demonstrated that G1-to-S phase cell cycle transition was significantly inhibited by pemafibrate. Pemafibrate attenuated serum-induced cyclin D1 expression in VSMCs. However, apoptosis was not induced by pemafibrate as assessed by the TUNEL assay. Similar to the in vitro data, VSMC proliferation was also decreased by pemafibrate in mice. These data suggest that pemafibrate attenuates neointima formation after vascular injury and VSMC proliferation by inhibiting cell cycle progression.

476-P: Pemafibrate, a PPAR Alpha Agonist, Attenuates Neointima Formation after Vascular Injury in Nondiabetic and Diabetic Mice

Recently, the prevention of cardiovascular events has become one of most important purpose of diabetes care. We have previously reported that GLP-1 receptor agonist exendin-4 (BBRC 2011) and DPP-4 inhibitor linagliptin (Cardiovasc Diabetol 2014) attenuate neiontima formation after vascular injury. On the other hand, PPAR agonist is also reported its vascular protective effect. Then, we examined whether selective PPAR alpha agonist pemafibrate could attenuate neointima formation after vascular injury and vascular smooth muscle cell (VSMC) proliferation. We performed endothelial denudation injury in mice treated with high fat diet (HFD) or normal chow. Orally administered pemafibrate significantly attenuated neointima formation after vascular injury in both HFD and normal chow mice. Interestingly, pemafibrate increased serum FGF-21 concentration and decreased serum insulin concentration in HFD mice. In addition, body weight was slightly but significantly decreased by pemafibrate in HFD mice. In vitro experiments, pemafibrate attenuated VSMC proliferation in growth curve in a dose dependent manner, but not another PPAR alpha agonist bezafibrate. This suggested that the attenuation of VSMC proliferation by pemafibrate could be the drug effect, not class effect of PPAR alpha agonist. BrdU assay revealed that pemafibrate inhibited DNA synthesis in VSMC dose-dependently. In cell cycle distribution, G1 to S phase entry was significantly inhibited by pemafibrate in flow cytometry analysis. However, apoptosis was not induced by pemafibrate in VSMC in TUNEL assay. These data suggested that pemafibrate attenuates neiontima formation after vascular injury and VSMC proliferation inhibiting cell cycle progression. Disclosure T. Horikawa: None. T. Nomiyama: None. H. Takahashi: None. T. Kawanami: None. Y. Hamaguchi: None. T. Tanaka: None. T. Yanase: None.

Thoracic epidural anaesthesia reduces insulin resistance and inflammatory response in experimental acute pancreatitis

Aims: The activity of the sympathetic nervous system (SNS) is crucial at an early stage in the development of an inflammatory reaction. A study of metabolic events globally and locally in the early phase of acute pancreatitis (AP), implying hampered SNS activity, is lacking.We hypothesized that thoracic epidural anaesthesia (TEA) modulates the inflammatory response and alleviates the severity of AP in pigs.Material and methods: The taurocholate (TC) group (n = 8) had only TC AP. The TC + TEA group (n = 8) had AP and TEA. A control group (n = 8) underwent all the preparations, without having AP or TEA. Metabolic changes in the pancreas were evaluated by microdialysis and by histopathological examination.Results: The relative increase in serum lipase concentrations was more pronounced in the TC group than in TC + TEA and control groups. A decrease in relative tissue oxygen tension (PtiO2) levels occurred one hour later in the TC + TEA group than in the TC group. The maintenance of normoglycaemia in the TC group required a higher glucose infusion rate than in the TC + TEA group. The relative decrease in serum insulin concentrations was most pronounced in the TC + TEA group.Conclusion: TEA attenuates the development of AP, as indicated by changes observed in haemodynamic parameters and by the easier maintenance of glucose homeostasis. Further, TEA was associated with attenuated insulin resistance and fewer local pathophysiological events.

Clinical trial of the effects of coenzyme Q10 supplementation on glycemic control and markers of lipid profiles in diabetic hemodialysis patients.

The current study was conducted to determine the effects of coenzyme Q10 (CoQ10) supplementation on glycemic control and markers of lipid profiles risk in diabetic hemodialysis (HD) patients. This randomized, double blind, placebo-controlled clinical trial was performed among 60 diabetic HD patients. Subjects were randomly allocated into two groups to take either 120mg/day of CoQ10 supplements or placebo (n = 30 each group) for 12 weeks. After 12 weeks of intervention, CoQ10 supplementation, compared with the placebo, resulted in a significant decrease in serum insulin concentrations (- 2.5 ± 4.0 vs. + 2.8 ± 5.3 µIU/mL, P < 0.001), homeostasis model of assessment-estimated insulin resistance (- 0.9 ± 2.1 vs. + 1.2 ± 3.0, P = 0.002), and significant increase in the quantitative insulin sensitivity check index (+ 0.009 ± 0.01 vs. - 0.02 ± 0.05, P = 0.003). In addition, a trend toward a greater decrease in serum triglycerides (- 5 ± 53 vs. + 17 ± 44, P = 0.078) and VLDL-cholesterol levels (- 0.9 ± 10 vs. + 3 ± 9, P = 0.078) was observed in the CoQ10 group compared to the placebo group. We did not observe any significant effect of CoQ10 supplementation on fasting glucose, HbA1c and other lipid profiles compared with the placebo. Overall, our study supported that CoQ10 supplementation to diabetic HD patients for 12 weeks had beneficial effects on markers of insulin metabolism, but did not affect fasting glucose, HbA1c, and lipid profiles. Clinical registration http://www.irct.ir : IRCT2016081811763N30.

Clinical Trial on the Effects of Vitamin D Supplementation on Metabolic Profiles in Diabetic Hemodialysis.

The current study was conducted to assess the effects of vitamin D supplementation on insulin metabolism, lipid fractions, biomarkers of inflammation, and oxidative stress in diabetic hemodialysis (HD) patients. This randomized double-blind placebo-controlled clinical trial was carried out among 60 diabetic HD patients. Subjects were randomly allocated into two groups to intake either oral vitamin D3 supplements at a dosage of 50 000 IU (n=30) or placebo (n=30) every 2 weeks for 12 weeks. After 12 weeks of intervention, subjects who received vitamin D supplements compared with the placebo had significantly decreased serum insulin concentrations (-3.4±3.7 vs. +2.0±4.2 μIU/ml, p<0.001), homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (-1.2±1.8 vs. +0.9±2.3, p<0.001), and improved quantitative insulin sensitivity check index (QUICKI) (+0.02±0.03 vs. -0.01±0.02, p<0.001). In addition, compared with the placebo, vitamin D supplementation led to significant reductions in serum high-sensitivity C-reactive protein (hs-CRP) (-1.4±2.5 vs. +1.4±4.8 mg/l, p=0.007), plasma malondialdehyde (MDA) (-0.1±0.2 vs. +0.1±0.2 μmol/l, p=0.009) and a significant increase in plasma total antioxidant capacity (TAC) concentrations (+33.8±56.7 vs. -2.0±74.5 mmol/l, p=0.04). We did not see any significant effect of vitamin D supplementation on lipid profiles and other biomarkers of inflammation and oxidative stress compared with the placebo. Overall, we found that vitamin D supplementation had beneficial effects on serum insulin, HOMA-IR, QUICKI, serum hs-CRP, plasma MDA, and TAC levels among diabetic HD patients for 12 weeks. CLINICAL REGISTRATION:: http://www.irct.ir: IRCT201611155623N92.

The Effect of Dietary Supplements Containing Green Tea, Capsaicin and Ginger Extracts on Weight Loss and Metabolic Profiles in Overweight Women: A Randomized Double-Blind Placebo-Controlled Clinical Trial

Background: This study was conducted to determine the effects of dietary supplements containing green tea, capsaicin and ginger extracts on weight loss and metabolic profiles among overweight women. Methods: This randomized double-blind placebo-controlled clinical trial was implemented among 50 overweight women. Participants were randomly divided into 2 groups. Group A received dietary supplements containing 125 mg green tea, 25 mg capsaicin and 50 mg ginger extracts (n = 25) group B received placebos (n = 25) twice with lunch and twice with dinner daily for 8 weeks. Results: Compared with placebo, taking dietary supplements containing green tea, capsaicin and ginger resulted in a significant decrease in weight (-1.8 ± 1.5 vs. +0.4 ± 1.2 kg, respectively, p < 0.001) and body mass index (BMI; -0.7 ± 0.5 vs. +0.1 ± 0.5 kg/m², respectively, p < 0.001). In addition, subjects who received green tea, capsaicin and ginger co-supplements had significantly decreased serum insulin concentrations (-2.6 ± 3.9 vs. -0.6 ± 2.0 µIU/mL, p = 0.02), homeostatic model of assessment for insulin resistance (-0.5 ± 0.8 vs. -0.05 ± 0.6, p = 0.01), and increased quantitative insulin sensitivity check index (+0.01 ± 0.01 vs. +0.001 ± 0.01, p = 0.008) and plasma glutathione (GSH) levels (+73.8 ± 120.6 vs. -28.3 ± 193.4 µmol/L, p = 0.03) compared with the placebo. Conclusions: Our study indicated that taking green tea, capsaicin and ginger co-supplements for 8 weeks among overweight women had beneficial effects on weight, BMI, markers of insulin metabolism and plasma GSH levels.

Effects of rumen-protected Capsicum oleoresin on productivity and responses to a glucose tolerance test in lactating dairy cows

The objective of this experiment was to investigate the effects of rumen-protected Capsicum oleoresin (RPC) supplementation on feed intake, milk yield and composition, nutrient utilization, fecal microbial ecology, and responses to a glucose tolerance test in lactating dairy cows. Nine multiparous Holstein cows were used in a replicated 3 × 3 Latin square design balanced for residual effects with three 28-d periods. Each period consisted of 14 d for adaptation and 14 d for data collection and sampling. Treatments were 0 (control), 100, and 200 mg of RPC/cow per day. They were mixed with a small portion of the total mixed ration and top-dressed. Glucose tolerance test was conducted once during each experimental period by intravenous administration of glucose at a rate of 0.3 g/kg of body weight. Dry matter intake was not affected by RPC. Milk yield tended to increase for RPC treatments compared to the control. Feed efficiency was linearly increased by RPC supplementation. Concentrations of fat, true protein, and lactose in milk were not affected by RPC. Apparent total-tract digestibility of dry matter, organic matter, and crude protein was linearly increased, and fecal nitrogen excretion was linearly decreased by RPC supplementation. Rumen-protected Capsicum oleoresin did not affect the composition of fecal bacteria. Glucose concentration in serum was not affected by RPC supplementation post glucose challenge. However, compared to the control, RPC decreased serum insulin concentration at 5, 10, and 40 min post glucose challenge. The area under the insulin concentration curve was also decreased 25% by RPC. Concentration of nonesterified fatty acids and β-hydroxybutyrate in serum were not affected by RPC following glucose administration. In this study, RPC tended to increase milk production and increased feed efficiency in dairy cows. In addition, RPC decreased serum insulin concentration during the glucose tolerance test, but glucose concentration was not affected by treatment.

Adiponectin Deficiency Impairs Maternal Metabolic Adaptation to Pregnancy in Mice.

Hypoadiponectinemia has been widely observed in patients with gestational diabetes mellitus (GDM). To investigate the causal role of hypoadiponectinemia in GDM, adiponectin gene knockout (Adipoq−/−) and wild-type (WT) mice were crossed to produce pregnant mouse models with or without adiponectin deficiency. Adenoviral vector–mediated in vivo transduction was used to reconstitute adiponectin during late pregnancy. Results showed that Adipoq−/− dams developed glucose intolerance and hyperlipidemia in late pregnancy. Increased fetal body weight was detected in Adipoq−/− dams. Adiponectin reconstitution abolished these metabolic defects in Adipoq−/− dams. Hepatic glucose and triglyceride production rates of Adipoq−/− dams were significantly higher than those of WT dams. Robustly enhanced lipolysis was found in gonadal fat of Adipoq−/− dams. Interestingly, similar levels of insulin-induced glucose disposal and insulin signaling in metabolically active tissues in Adipoq−/− and WT dams indicated that maternal adiponectin deficiency does not reduce insulin sensitivity. However, remarkably decreased serum insulin concentrations were observed in Adipoq−/− dams. Furthermore, β-cell mass, but not glucose-stimulated insulin release, in Adipoq−/− dams was significantly reduced compared with WT dams. Together, these results demonstrate that adiponectin plays an important role in controlling maternal metabolic adaptation to pregnancy.

An Alteration in the Cecal Microbiota Composition by Feeding of 1-Kestose Results in a Marked Increase in the Cecal Butyrate Content in Rats.

Functional food ingredients, including prebiotics, have been ardently developed for improving the intestinal environment. Fructooligosaccarides (FOS), including fructans, are the well researched and commercialized prebiotics. However, to our knowledge, few studies have been conducted on the physiological effects of each component of FOS as prebiotics. 1-Kestose, a component of FOS, is composed of one glucose and two fructose molecules, and is considered as a key prebiotic component in short-chain FOS. In the present study, we examined the effects of dietary 1-kestose using 0.5–5% 1-kestose diets on cecal microbiota composition and cecal contents of short-chain fatty acids and lactate in rats. The findings indicate that dietary 1-kestose induced cecal hypertrophy and alterations in the cecal microbiota composition, including a marked increase in the cell number of Bifidobacterium spp. These alterations were associated with significant increases in acetate and lactate, and a marked increase in butyrate in cecal contents. Furthermore, dietary 1-kestose induced a significant decrease in serum insulin concentration in rats fed 2.5–5% 1-kestose diet. These findings suggest a potential of 1-kestose to be a prebiotic for improving the metabolism of the host.

Effects of Probiotic Supplementation on Metabolic Status in Pregnant Women: a Randomized, Double-blind, Placebo-Controlled Trial.

Limited data is available on the effects of multispecies probiotic supplementation on metabolic status in pregnant women in the first half of pregnancy. The current study was carried out to determine the effects of multispecies probiotic capsule supplementation on metabolic status among pregnant women in the first half of pregnancy. A randomized clinical trial was conducted among 60 pregnant women aged 18-37 years. The participants were randomly divided into two groups: group A (n = 30) received multispecies probiotic supplements containing three probiotic bacteria spices Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum (2 × 109 CFU/g each) and group B (n = 30) received placebo from 9 weeks of gestation for a duration of 12 weeks. Fasting blood samples were taken at the beginning of the study and after 12 weeks of intervention to determine metabolic profiles, inflammatory cytokines and biomarkers of oxidative stress. After 12 weeks of intervention, compared to the placebo group, the pregnant women who consumed probiotic capsule had significantly decreased serum insulin concentrations (-1.5 ± 4.8 vs. +1.3 ± 5.2 µIU/mL, P = 0.03), the homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (-0.3 ± 0.9 vs. +0.3 ± 1.1, P = 0.04), the homeostasis model of assessment-estimated b cell function (HOMA-B) (-7.2 ± 23.1 vs. +5.3 ± 22.6, P = 0.03) and increased quantitative insulin sensitivity check index (QUICKI) (+0.01 ± 0.05 vs. -0.01 ± 0.02, P = 0.03). In addition, changes in serum triglycerides levels (-14.7 ± 46.5 vs. +37.3 ± 74.2 mg/dL, P = 0.002), high-sensitivity C-reactive protein (hs-CRP) (-1.0 ± 2.6 vs. +1.7 ± 4.3 mg/L, P = 0.004), plasma nitric oxide (NO) (+6.8 ± 9.3 vs. -4.7 ± 7.4 µmol/L, P < 0.001), total antioxidant capacity (TAC) (+171.9 ± 187.6 vs. -51.9 ± 208.8 mmol/L, P < 0.001) and glutathione (GSH) concentrations (+34.3 ± 71.6 vs. -36.9 ± 108.3 µmol/L, P = 0.004) in supplemented women were significantly different from those of the placebo group. However, after controlling for baseline levels, age and BMI at the study baseline, the changes in plasma GSH were not significantly different between the groups. Overall, probiotic supplementation for 12 weeks among pregnant women in the first half of pregnancy had beneficial effects on markers of insulin metabolism, triglycerides, biomarkers of inflammation and oxidative stress.

Grape Seed Extract Supplementation and the Effects on the Biomarkers of Oxidative Stress and Metabolic Profiles in Female Volleyball Players: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BackgroundOnly limited data are available for evaluating the effects of the administration of grape seed extract (GSE) on the metabolic status of female volleyball players.ObjectivesThis study was conducted to determine the effects of GSE administration on the metabolic status of female volleyball players.MethodsThis randomized, double-blind, placebo-controlled clinical trial was performed among 40 female volleyball players. The subjects were randomly divided into two groups, with members of the test group (n = 20) taking 300 mg of GSE twice a day for eight weeks and members of the control group (n = 20) taking a placebo pearl for the same period. Fasting blood samples were taken before and after the eight-week intervention period in order to determine the related variables.ResultsSupplementation with GSE resulted in a significant rise in the plasma glutathione (GSH) level (+265.5 ± 344.2 vs. +2.2 ± 378.2 µmol/L, P = 0.02), as well as a significant decrease in the malondialdehyde (MDA) level (-1.4 ± 2.0 vs. -0.2 ± 1.2 µmol/L, P = 0.01) when compared to the placebo group. In addition, when compared to the group that received the placebo, the subjects who received GSE had significantly decreased serum insulin concentrations (-23.4 ± 23.4 vs. +1.8 ± 25.2 pmol/L, P = 0.002), a decreased homeostasis model of assessment for insulin resistance (HOMA-IR) (-0.7 ± 0.7 vs. +0.2 ± 0.9, P = 0.002), and an increased quantitative insulin sensitivity check index (QUICKI) (+0.01 ± 0.01 vs. -0.01 ± 0.02, P = 0.03). The administration of GSE had no significant effects on creatine phosphokinase (CPK), total antioxidant capacity (TAC), nitric oxide (NO), fasting plasma glucose (FPG), and lipid concentrations when compared with the administration of the placebo. However, after controlling for baseline NO levels, age, and baseline BMI, the changes in the plasma NO concentrations were significantly different between the two groups.ConclusionsIn conclusion, taking GSE for eight weeks had beneficial effects on the plasma GSH, MDA levels, and markers of insulin metabolism of female volleyball players.

Anti-diabetic and anti-oxidant potential of aged garlic extract (AGE) in streptozotocin-induced diabetic rats.

BackgroundAlthough aged garlic extract (AGE) shares some active components with fresh garlic and in spite of its palatability and milder side effects, the anti-diabetic and related anti-oxidant properties of AGE have not been investigated extensively, and the reported findings are inconsistent.This study investigated the anti-diabetic effects of 3 incremental doses of AGE in streptozotocin (STZ)-induced diabetic rats (fasting blood sugar > 20 mM).MethodDiabetic rats were divided into a control diabetic group (CD) and AGE-treated diabetic group (AGE-D). The AGE-D was divided into 3 groups and accordingly treated with AGE i.p. at 100, 300 and 600 mg/kg daily for 8 weeks. A control normal group (CN) was also included for reference.ResultsCompared to the CN group, the CD group showed significant loss of body weight (over 50 %); and decreased serum insulin concentration (10 fold) and total anti-oxidant level and catalase activity (45–70 %) in serum, kidney and liver. Conversely, the CD rats had an elevated blood glucose (nearly 4 fold), serum cholesterol (nearly 2 fold) and triglycerides (>2 fold), erythrocyte glycated hemoglobin (GHb, 3 fold) and kidney and liver lipid peroxidation (MDA levels). Treatment with AGE positively reversed the diabetic changes in the targeted parameters to levels significantly lower than those measured in the CD group and the degrees of attenuation were almost dose dependent especially with the two higher doses.ConclusionAGE exhibits a dose-dependent ameliorative action on indicators of diabetes in STZ-induced diabetic rats.

The impact of iron content in a diet high in fat, fructose, and salt on metabolic state and mineral status of rats

The purpose of the study was to assess the influence of dietary iron content on lipid and carbohydrate metabolism and on zinc and copper status in rats fed with a diet high in fat, fructose, and salt. Wistar rats were fed with diets high in fat, fructose, and salt, containing differing amounts of iron, namely, deficit, normal, and high levels. After 6 weeks, the animals were weighed and killed. The liver, heart, and pancreas were collected, as were blood samples. The total cholesterol, triglycerides, fasting glucose, and insulin levels in the serum were measured. The iron, zinc, and copper concentrations in tissues and serum were determined. It was found that in rats fed with the iron-deficit diet, cholesterol and glucose profiles improved. Both deficit and excess iron in the diet decreased insulin concentration in rats and disturbed iron, zinc, and copper status. High-iron level in the diet decreased the relative mass of the pancreas. In conclusion, the decrease in serum insulin concentration observed in rats fed with the modified diet high in iron was associated with iron and copper status disorders, and also, with a relatively diminished pancreas mass. A deficit of iron in the diet improved lipid and carbohydrate metabolism in rats.

Maternal Exercise During Pregnancy Improves Glucose Metabolism of Offspring

The intrauterine environment during pregnancy is a critical factor in the development of diabetes and obesity in offspring. To determine the effects of maternal exercise during pregnancy on the metabolic health of offspring, 6wk old C57BL/6 virgin female mice were fed a chow or high‐fat (HF) (60%) diet and divided into 4 sub‐groups: Trained (housed with running wheels for 2wks preconception and during gestation); Pre‐Pregnancy Trained (housed with running wheels for 2wks pre‐conception); Gestation Trained (housed with running wheels during gestation); or Sedentary (static cages). Breeders were sedentary and chow‐fed. Offspring were sedentary, chow‐fed and studied for 12 months. From 6 months on, male offspring from Trained dams had decreased serum insulin concentrations, improved glucose tolerance, and decreased % body fat vs. all other groups. This improved metabolic profile occurred in offspring of both chow‐ and HF‐fed dams. Female offspring had similar responses. 12 month old offspring from Trained dams had significant changes in hepatic expression of key genes regulating Krebs cycle activity and fatty acid oxidation, suggesting liver adaptations are central for this effect. In conclusion, maternal exercise before and during pregnancy in mice has profound effects to improve the metabolic health of offspring. Thus, maternal exercise may combat the increasing rates of diabetes and obesity.

Effect of broccoli sprouts on insulin resistance in type 2 diabetic patients: a randomized double-blind clinical trial

Use of antioxidant components is a new approach for improvement of insulin resistance (IR) as a main feature of type 2 diabetes and its complications. The aim of this study was to investigate the effects of broccoli sprouts powder (BSP) containing high concentration of sulphoraphane on IR in type 2 diabetic patients. Eighty-one patients were randomly assigned to receive 10 g/d BSP (A, n = 27), 5 g/d BSP (B, n = 29) and placebo (C, n = 25) for 4 weeks. Fasting serum glucose and insulin concentration, glucose to insulin ratio and homoeostasis model assessment of IR (HOMA-IR) index were measured at baseline and again 4 weeks after treatment. Seventy-two patients completed the study and 63 were included in the analysis. After 4 weeks, consumption of 10 g/d BSP resulted in a significant decrease in serum insulin concentration and HOMA-IR (p = 0.05 for treatment effect). Therefore, broccoli sprouts may improve IR in type 2 diabetic patients.

Testosterone deficiency impairs glucose oxidation through defective insulin and its receptor gene expression in target tissues of adult male rats

Testosterone and insulin interact in their actions on target tissues. Most of the studies that address this issue have focused on the physiological concentration of testosterone, which maintains normal insulin sensitivity but has deleterious effects on the same when the concentration of testosterone is out of this range. However, molecular basis of the action of testosterone in the early step of insulin action is not known. The present study has been designed to assess the impact of testosterone on insulin receptor gene expression and glucose oxidation in target tissues of adult male rat. Adult male albino rats were orchidectomized and supplemented with testosterone (100 μg/100 g b. wt., twice daily) for 15 days from the 11th day of post orchidectomy. On the day after the last treatment, animals were euthanized and blood was collected for the assay of plasma glucose, serum testosterone and insulin. Skeletal muscles, such as gracilis and quadriceps, liver and adipose tissue were dissected out and used for the assay of various parameters such as insulin receptor concentration, insulin receptor mRNA level and glucose oxidation. Testosterone deprivation due to orchidectomy decreased serum insulin concentration. In addition to this, insulin receptor number and its mRNA level and glucose oxidation in target tissues were significantly decreased ( p < 0.05) when compared to control. However, testosterone replacement in orchidectomized rats restored all these parameters to control level. It is concluded from this study that testosterone deficiency-induced defective glucose oxidation in skeletal muscles, liver and adipose tissue is mediated through impaired expression of insulin and its receptor gene.