Increased Insulin Sensitivity Index Research Articles

Flaxseed extract: A potential therapeutic intervention for type-2 diabetes mellitus and cardiovascular risk reduction in Wistar rats

Introduction: Type 2 diabetes mellitus (T2DM) affects millions of people worldwide, highlighting the importance of dietary interventions. Flaxseed (Linum usitatissimum L.) has shown promise in treating chronic metabolic diseases. This study investigates the therapeutic potential of flaxseed as an antidiabetic agent and its protective effect on cardiovascular diseases. Methods: Rats were randomly divided into five groups: normal fed with drug carrier group (N), diabetes with drug carrier group (D), diabetes with metformin (M) group (D+M), and diabetes with flaxseed extract doses of 100 and 200 mg/kg (D+F1 and D+F2) groups. The diabetic rat model was established by administration of drinking water containing 25% fructose and a single intraperitoneal injection of 100 mg/kg alloxan. After a six-week intervention, the rats were sacrificed to assess the antidiabetic and cardiovascular effects. Results: The doses of 100 and 200 mg/kg flaxseed extract significantly reduced body weight and fasting glucose levels and increased insulin sensitivity index (KITT) compared to the diabetes group (P<0.05). In addition, histological analysis showed a significant improvement and increase in pancreatic beta cells in the treatment group compared to the diabetes group (P<0.05). Flaxseed extract doses of 100 and 200 mg/kg significantly reduced weight gain and insulin resistance, contributing to decreased arterial stiffness and atherogenic index compared to the diabetic group (P<0.05). The hypoglycemic effect suggested a dose-dependent response. Conclusion: Flaxseed extract regulates blood glucose levels probably by enhancing insulin sensitivity and revitalizing damaged pancreatic beta cells. It mitigates cardiovascular risk, by reducing arterial stiffness and atherogenicity.

Cardiovascular and metabolic effects of MANP. a novel GC-A activator, in human hypertension with metabolic syndrome

Abstract Background/Introduction Hypertension (HTN) and metabolic syndrome (MetS) are both leading risk factors for major cardiovascular diseases, which frequently coexist as a complicated cardiometabolic disorder. The cardiac hormone atrial natriuretic peptide (ANP) plays a key role in both blood pressure and metabolic regulation through activation of the guanylyl cyclase-A receptor (GC-A) and the second messenger 3’,5’ cyclic guanosine monophosphate (cGMP). Indeed, ANP decreases blood pressure, induces lipolysis by increasing plasma levels of non-esterified fatty acids (NEFA) and improves insulin-sensitivity. MANP is a new Mayo Clinic designed natriuretic peptide consisting of the native ANP with a 12-amino-acid C-terminus extension and its biological actions are mediated by the GC-A/cGMP pathway. MANP is less susceptible to neprilysin degradation and exert more sustained cGMP dependent biological actions than ANP. Purpose In a proof-of-principle human study, for the first time we aimed to determine the cardiovascular and metabolic properties of MANP, a novel ANP analog, in the clinical setting of HTN with MetS. Methods We conducted a double-blind, placebo-controlled trial in 22 patients (17 receiving MANP) with HTN and MetS involving single subcutaneous injection of MANP (2.5 µg/kg) or placebo (NCT03781739). Blood pressure (BP) and circulating cGMP were monitored for 24 hours post treatment. Circulating metabolic parameters including insulin, glucose, non-esterified fatty acids (NEFA) and insulin resistance (HOMA-IR) and insulin sensitivity (HOMA-IS) indexes were assessed for the first 4 hours post treatment. Results Compared to baseline, MANP increased plasma cGMP at 30 minutes (delta: 4.8 ± 2.0 pmol/mL, P = 0.02) and 1 hour (delta: 2.9 ± 1.3 pmol/mL, P = 0.03) post injection. At 6 hours, systolic BP decreased by 5.7 ± 2.9 mmHg (P = 0.06) in the MANP group, whereas no reduction in BP was observed in placebo group. Among the 17 subjects receiving MANP, lower baseline cGMP levels were associated with greater mean reductions in systolic BP (ρ = 0.66, P = 0.005). After MANP injection, glucose levels decreased at 2 (delta: -4.7 ± 2.1 mg/mL, P = 0.04) and 4 hours (delta: -13.1 ± 3.9 mg/mL, P = 0.003) compared to baseline while insulin levels remained stable. During the first 4 hours post injection, we also observed a trend of increase in insulin sensitivity index (HOMA2-IS) and decrease in insulin resistance index (HOMA2-IR) with MANP, both were opposite to the trends in placebo. At 1 hour post MANP administration, NEFA increased by 108.2 ± 37.4 µM compared to baseline (P = 0.01). Conclusion(s) Our findings support the favorable cardiovascular and metabolic actions of MANP as a potential therapeutic strategy for HTN with MetS.

Genetic evidence that high BMI in childhood has a protective effect on intermediate diabetes traits, including measures of insulin sensitivity and secretion, after accounting for BMI in adulthood

Aims/hypothesisDetermining how high BMI at different time points influences the risk of developing type 2 diabetes and affects insulin secretion and insulin sensitivity is critical.MethodsBy estimating childhood BMI in 441,761 individuals in the UK Biobank, we identified which genetic variants had larger effects on adulthood BMI than on childhood BMI, and vice versa. All genome-wide significant genetic variants were then used to separate the independent genetic effects of high childhood BMI from those of high adulthood BMI on the risk of type 2 diabetes and insulin-related phenotypes using Mendelian randomisation. We performed two-sample MR using external studies of type 2 diabetes, and oral and intravenous measures of insulin secretion and sensitivity.ResultsWe found that a childhood BMI that was one standard deviation (1.97 kg/m2) higher than the mean, corrected for the independent genetic liability to adulthood BMI, was associated with a protective effect for seven measures of insulin sensitivity and secretion, including increased insulin sensitivity index (β=0.15; 95% CI 0.067, 0.225; p=2.79×10−4) and reduced fasting glucose levels (β=−0.053; 95% CI −0.089, −0.017; p=4.31×10−3). However, there was little to no evidence of a direct protective effect on type 2 diabetes (OR 0.94; 95% CI 0.85, 1.04; p=0.228) independently of genetic liability to adulthood BMI.Conclusions/interpretationOur results provide evidence of the protective effect of higher childhood BMI on insulin secretion and sensitivity, which are crucial intermediate diabetes traits. However, we stress that our results should not currently lead to any change in public health or clinical practice, given the uncertainty regarding the biological pathway of these effects and the limitations of this type of study.Graphical

Effect of Denosumab on Glucose Homeostasis in Postmenopausal Women with Breast Cancer Treated with Aromatase Inhibitors: A Pilot Study.

Background Aromatase inhibitors in women with breast cancer have been associated with cancer treatment-induced bone loss (CTIBL), increased fracture risk, and impairment of glucose metabolism. Denosumab (Dmab), a monoclonal antibody against RANKL, which is a key regulator of the osteoclast activity, is effective as an antiresorptive agent in the treatment of CTIBL. Since RANKL/RANK pathway may contribute to the pathogenesis of glucometabolic disorders, it has been suggested that Dmab may improve glucose homeostasis. Our pilot study evaluated the effect of a single administration of 60 mg Dmab on glucose metabolism in a cohort of women with breast cancer treated with aromatase inhibitors. Methods Fifteen postmenopausal nondiabetic women were prospectively enrolled. Oral glucose tolerance test (OGTT) and metabolic parameters, including FGF21, were assessed at baseline and one month after Dmab injection. Midterm glucose control was evaluated by measuring glycated haemoglobin (HbA1c) levels 5 months after Dmab. Results Parameters of glucose metabolism were not different one month after Dmab but circulating FGF21 levels significantly decreased (128.5 ± 46.8 versus 100.2 ± 48.8 pg/mL; p=0.016). Considering patients with insulin resistance at baseline (HOMA-IR > 2.5 and Matsuda Index < 2.5; n = 5), reduced mean fasting insulin levels (16.3 ± 4.9 versus 13.5 ± 3.5 mcU/mL; p=0.029) and increased insulin sensitivity index QUICKI (0.317 ± 0.013 versus 0.327 ± 0.009; p=0.025) were found. Nonetheless, HbA1c increased 5 months after Dmab (36.0 ± 2.3 versus 39.6 ± 3.1 mmol/mol; p=0.01). Conclusions Although RANKL blockade induced a short-term positive effect on insulin sensitivity, particularly in insulin-resistant patients, a benefit on long-term glucose metabolism was not evident. In conclusion, Dmab is safe for glucose metabolism in aromatase inhibitor-treated women with breast cancer.

Effects of high-intensity interval training and nutrition advice on cardiometabolic markers and aerobic fitness in adolescent girls with obesity.

The aim of the study was to compare the effects of high-intensity interval training (HIIT) and nutrition advice on cardiometabolic biomarkers, hormonal parameters, and cardiorespiratory fitness in adolescent girls with obesity. Adolescent girls with obesity (n = 44, aged 13-19 years) were randomized into a 12-week intervention as follows: (i) dietary advice and HIIT (n = 22), and (ii) dietary advice only (n = 22). The concentration of biomarkers of inflammation, biochemical and hormonal testing, oral glucose tolerance test, cardiorespiratory fitness, physical activity levels, and nutrition were assessed. After a 3-month intervention, the diet+HIIT group significantly increased insulin sensitivity index (-0.34 ± 1.52 vs. 1.05 ± 3.21; p = 0.001) and work load (0.6 ± 11.3 W vs. 14.6 ± 20.2 W; p = 0.024) and decreased glucose area under the curve (-0.29 ± 4.69 vs. -0.98 ± 4.06; p = 0.040), insulin area under the curve (-9.65 ± 117.9 vs. -98.7 ± 201.8; p = 0.003), and high-sensitivity C-reactive protein (hs-CRP) (0.12 ± 1.92 mg/L vs. -1.47 ± 3.67 mg/L; p = 0.039) in comparison with the diet group. Regarding within-group changes, both groups had significant improvements in body mass index (BMI), BMI-standard deviation score, body fat percentage, and systolic blood pressure. Positive impact on waist circumference, waist circumference/height ratio, diastolic blood pressure, hs-CRP, work load, maximal heart rate, and resting heart rate was observed only after the diet+HIIT intervention. No significant change was noted in peak oxygen uptake, lipid profile, and hormonal parameters between groups after intervention. Novelty HIIT and nutrition advice increased insulin sensitivity and decreased BMI, body fat, systolic blood pressure, and diastolic blood pressure. Nutrition advice decreased BMI, body fat, and systolic blood pressure in adolescent girls with obesity.

Diosgenin and Its Fenugreek Based Biological Matrix Affect Insulin Resistance and Anabolic Hormones in a Rat Based Insulin Resistance Model.

Fenugreek is known since ancient times as a traditional herbal medicine of its multiple beneficial effects. Fenugreek's most studied and employed effect is its hypoglycemic property, but it can also be useful for the treatment of certain thyroid disorders or for the treatment of anorexia. The regulation of glucose homeostasis is a complex mechanism, dependent on the interaction of different types of hormones and neurotransmitters or other compounds. For the study of how diosgenin and fenugreek seeds modify insulin sensitivity, we used a rat insulin resistance model induced by high-fat diet. Diosgenin in three different doses (1mg/bwkg, 10mg/bwkg, and 50 mg/bwkg, respectively) and fenugreek seed (0.2 g/bwkg) were administered orally for 6 weeks. Insulin sensitivity was determined by hyperinsulinemic euglycemic glucose clamp method. Our research group found that although glucose infusion rate was not significantly modified in either group, the increased insulin sensitivity index and high metabolic clearance rate of insulin found in the 1 mg/kg diosgenin and the fenugreek seed treated group suggested an improved peripheral insulin sensitivity. Results from the 10 mg/kg diosgenin group, however, suggest a marked insulin resistance. Fenugreek seed therapy results on the investigated anabolic hormones support the theory that, besides insulin and gastrointestinal peptides, the hypothalamic-hypopituitary axis regulated hormones synchronized action with IGF-1 also play an important role in the maintaining of normal glucose levels. Both diosgenin and fenugreek seeds are capable of interacting with substrates of the above-mentioned regulatory mechanisms, inducing serious hormonal disorders. Moreover, fenugreek seeds showed the ability to reduce the thyroid hormone levels at the periphery and to modify the T4/T3 ratio. It means that in healthy people this effect could be considered a severe side effect; however, in hypothyroidism this effect represents a possibility of alternative natural therapy.

Propionate Affects Insulin Signaling and Progesterone Profiles in Dairy Heifers

Emerging data highlighting gut microbiome influences on health support evaluation of how microbial fermentation end-products influence postabsorptive systems. This study aimed to investigate the effect of increased propionate status on progesterone profiles and insulin sensitivity in dairy heifers. Eleven Holstein heifers, synchronized in estrus, were assigned to one of two continuous, 5-day IV treatments: sodium propionate (PRO; n = 5) or saline (CON; n = 6). These infusions culminated in a hyperglycemic clamp with daily blood samples for an additional 7 days. Plasma propionate concentrations increased over the first 9 h in PRO heifers, then decreased until day 3 when they matched CON heifers. Maximum plasma progesterone concentrations tended to be greater in PRO heifers than CON heifers (4.19 vs 3.73 ng/mL; P = 0.087). Plateau insulin concentrations in CON animals were significantly greater than those in PRO animals (249.4 ± 25.1 vs 123.9 ± 35.8; P = 0.008) with a trend for an increased insulin sensitivity index in PRO heifers compared to CON heifers (P = 0.06). These changes in plasma propionate clearance leading to increased progesterone response and changes in insulin sensitivity suggest a role for SCFA metabolism in reproductive hormone regulation.

Metabolic effects of Lactobacillus reuteri DSM 17938 in people with type 2 diabetes: A randomized controlled trial.

To investigate the metabolic effects of 12-week oral supplementation with Lactobacillus reuteri DSM 17938 in patients with type 2 diabetes on insulin therapy. In a double-blind trial, we randomized 46 people with type 2 diabetes to placebo or a low (108 CFU/d) or high dose (1010 CFU/d) of L. reuteri DSM 17938 for 12 weeks. The primary endpoint was the effect of supplementation on glycated haemoglobin (HbA1c). Secondary endpoints were insulin sensitivity (assessed by glucose clamp), liver fat content, body composition, body fat distribution, faecal microbiota composition and serum bile acids. Supplementation with L. reuteri DSM 17938 for 12 weeks did not affect HbA1c, liver steatosis, adiposity or microbiota composition. Participants who received the highest dose of L. reuteri exhibited increases in insulin sensitivity index (ISI) and serum levels of the secondary bile acid deoxycholic acid (DCA) compared with baseline, but these differences were not significant in the between-group analyses. Post hoc analysis showed that participants who responded with increased ISI after L. reuteri supplementation had higher microbial diversity at baseline, and increased serum levels of DCA after supplementation. In addition, increases in DCA levels correlated with improvement in insulin sensitivity in the probiotic recipients. Intake of L. reuteri DSM 17938 for 12 weeks did not affect HbA1c in people with type 2 diabetes on insulin therapy; however, L. reuteri improved insulin sensitivity in a subset of participants and we propose that high diversity of the gut microbiota at baseline may be important.

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency.

The visceral adiposity index, based on anthropometric and metabolic parameters, has been shown to be related to adipose tissue function and insulin sensitivity. We aimed to evaluate the performance of the visceral adiposity index in adult patients with growth hormone deficiency. We enrolled 52 patients(mean age 51 ± 13 years) with newly diagnosed growth hormone deficiency and 50 matched healthy subjects as controls at baseline. At baseline and after 12 and 24 months of treatment we evaluated anthropometric measures, lipid profile, glucose and insulin during an oral glucose tolerance test, hemoglobin A1c, homeostasis model assessment estimate of insulin resistance, quantitative insulin sensitivity check index, insulin sensitivity index Matsuda, insulin-like growth factor-I and visceral adiposity index. At baseline growth hormone deficiency patients showed higher waist circumference (p < 0.001), low-density lipoprotein cholesterol (p < 0.001) and visceral adiposity index (p = 0.003) with lower insulin sensitivity index (p = 0.007) and high-density lipoprotein cholesterol (p = 0.001) than controls. During growth hormone treatment we observed a significant increase in insulin-like growth factor-I (p < 0.001), high-density lipoprotein (p < 0.001) with a trend toward increase in insulin sensitivity index (p = 0.055) and a significant decrease in total cholesterol (p < 0.001) and visceral adiposity index (p < 0.001), while no significant changes were observed in other clinical and metabolic parameters. The visceral adiposity index was the only parameter that significantly correlated with growth hormone peak at diagnosis (p < 0.001) and with insulin-like growth factor-I and insulin sensitivity index both at diagnosis (p = 0.009 and p < 0.001) and after 12 (p = 0.026 and p = 0.001) and 24 months (p < 0.001 and p = 0.001) of treatment. The visceral adiposity index, which has shown to be associated with both insulin-like growth factor-I and insulin sensitivity, proved to be the most reliable index of metabolic perturbation, among the most common indexes of adiposity assessment and a marker of benefit during treatment in adult growth hormone deficiency patients.

Exercise improved lipid metabolism and insulin sensitivity in rats fed a high-fat diet by regulating glucose transporter 4 (GLUT4) and musclin expression.

This study aimed to evaluate the effects of exercise training on triglyceride deposition and the expression of musclin and glucose transporter 4 (GLUT4) in a rat model of insulin resistance. Thirty male Sprague-Dawley rats (8 weeks old, weight 160±10 g) were fed a high-fat diet (40% calories from fat) and randomly divided into high-fat control group and swimming intervention group. Rats fed with standard food served as normal control. We found that 8-week swimming intervention significantly decreased body weight (from 516.23±46.27 to 455.43±32.55 g) and visceral fat content (from 39.36±2.50 to 33.02±2.24 g) but increased insulin sensitivity index of the rats fed with a high-fat diet. Moreover, swimming intervention improved serum levels of TG (from 1.40±0.83 to 0.58±0.26 mmol/L) and free fatty acids (from 837.80±164.25 to 556.38±144.77 μEq/L) as well as muscle triglycerides deposition (from 0.55±0.06 to 0.45±0.02 mmol/g) in rats fed a high-fat diet. Compared with rats fed a standard food, musclin expression was significantly elevated, while GLUT4 expression was decreased in the muscles of rats fed a high-fat diet. In sharp contrast, swimming intervention significantly reduced the expression of musclin and increased the expression of GLUT4 in the muscles of rats fed a high-fat diet. In conclusion, increased musclin expression may be associated with insulin resistance in skeletal muscle, and exercise training improves lipid metabolism and insulin sensitivity probably by upregulating GLUT4 and downregulating musclin.

The effect of vitamin K1 supplementation on sensitivity and insulin resistance via osteocalcin in prediabetic women: a double-blind randomized controlled clinical trial.

A relationship between osteocalcin (OC) levels and factors associated with energy metabolism and insulin resistance has been reported recently. The aim of this study was to investigate whether modulation of ostecalcin isoforms via vitamin K1 supplementation would affect glucose metabolism or insulin sensitivity in prediabetic and premenopause women. Eighty-two prediabetic women were randomized to consume vitamin K1 supplement (n = 39) or placebo (n = 43) for 4 weeks. Participants in the vitamin K1 supplement group received one pearl softgel capsule containing 1000 μm of phylloquinone, and the placebo group received one placebo capsule daily for 4 weeks. Blood samples were collected at baseline and after the 4-week intervention period to quantify carboxylated OC (cOC), undercarboxylated OC (ucOC) and relevant variables. Phylloquinone supplementation increased the serum levels of cOC and decreased ucOC, compared with placebo (12.53 ± 5.95 compared with 7.43 ± 4.85 ng/ml and 2.47 ± 1.91 compared with 4.79 ± 2.43 ng/ml, respectively; P < 0.001). Furthermore, intake of phylloquinone supplement led to significant decreases in %ucOC (17.97 ± 12.24 compared with 43.80 ± 19.86) and 2-h post-oral glucose tolerance test (OGTT) glucose (7.32 ± 1.50 compared with 8.62 ± 1.45 mmol/l), and 2-h post-OGTT insulin level (80.34 ± 42.24 compared with 112.43 ± 53.19 μIU/ml) and increased insulin sensitivity index (2.46 ± 0.71 compared with 1.75 ± 0.61) compared with placebo. Overall, a significant association was found between changes in %ucOC and changes in 2-h post-OGTT glucose (r = 0.308, P = 0.028). The results of this study demonstrated that vitamin K1 supplementation for 4 weeks did not affect insulin resistance in premenopausal and prediabetic women but had beneficial effects on glycemic status and insulin sensitivity.

Mechanisms behind the superior effects of interval vs continuous training on glycaemic control in individuals with type 2 diabetes: a randomised controlled trial.

By use of a parallel and partly crossover randomised, controlled trial design we sought to elucidate the underlying mechanisms behind the advantageous effects of interval walking training (IWT) compared with continuous walking training (CWT) on glycaemic control in individuals with type 2 diabetes. We hypothesised that IWT, more than CWT, would improve insulin sensitivity including skeletal muscle insulin signalling, insulin secretion and disposition index (DI). By simple randomisation (sequentially numbered, opaque sealed envelopes), eligible individuals (diagnosed with type 2 diabetes, no exogenous insulin treatment) were allocated to three groups: a control group (CON, n = 8), an IWT group (n = 12) and an energy expenditure-matched CWT group (n = 12). Training groups were prescribed free-living training, five sessions per week (60 min/session). A three-stage hyperglycaemic clamp, including glucose isotope tracers and skeletal muscle biopsies, was performed before and after a 4 month intervention in a hospitalised setting. No blinding was performed. The improved glycaemic control, which was only seen in the IWT group, was consistent with IWT-induced increases in insulin sensitivity index (49.8 ± 14.6%; p < 0.001), peripheral glucose disposal (14.5 ± 4.9%; p < 0.05) and DI (66.2 ± 21.8%; p < 0.001), with no changes in the CWT or CON group. Moreover, only IWT improved insulin signalling in skeletal muscle via increased insulin-stimulated phosphorylation of AS160 (29.0 ± 10.8%; p < 0.05). No changes were seen in insulin secretion during hyperglycaemia alone, hyperglycaemia + glucagon-like peptide 1 infusion or arginine injection. IWT maintains insulin secretion and improves insulin sensitivity and DI, in contrast to energy expenditure-matched CWT. These results suggest that training with alternating intensity, and not just training volume and mean intensity, is a key determinant of changes in whole body glucose disposal in individuals with type 2 diabetes. ClinicalTrials (NCT01234155).

Modulation of fasting blood glucose by raw banana powder in alloxan-induced diabetic rats

This study aimed to observe the influence of raw banana powder (RBP) on fasting blood glucose (FBG), blood lipid and other biochemical indicators in type-2 diabetic rats and therefore to provide experimental evidences for developing suitable food from banana powder for diabetic patients. Eight Sprague-Dawley rats were selected randomly as the normal control group (NCG) before the experiment. After establishing type-2 diabetic rat models (11.1-16.7 mmoL/L) by alloxan, 32 rats were divided into four groups: the diabetic control group (DCG, n=8), low-dose group (LDG, n=8), middle-dose group (MDG, n=8) and high-dose group (HDG, n=8). The LDG, MDG and HDG rats received gastric perfusion of RBP at the doses of 2 g/kg, 4 g/kg and 6 g/kg per day, respectively. After four weeks, oral glucose tolerance test was carried out in each group, and then the FBG level, blood lipid, insulin, short chain fatty acids content, pH value of colon content and other biochemical indicators of rats in each group were determined and compared among the groups. Results showed that the levels of FBG significantly decreased in the LDG (11.97+-0.83), MDG (8.95+-0.45) and HDG (9.28+-1.45), compared with their initial values (13.00+-1.25, 13.68+-0.75 and 13.91+-0.80, respectively). The FBG levels in these three groups were obviously lower than that in the DCG. However, there were no dramatic FBG changes in the NCG and DCG (5.77+-0.59, 14.14+-0.72) compared with the initial stage (5.55+-0.23, 13.93+-0.47). The RBP intervention increased insulin-sensitivity index and regulated postprandial blood glucose. Besides, RBP showed the positive effects on symptoms of type 2 diabetic rats, such as the reduction of weight gain and total cholesterol.

Lifetime congenital isolated GH deficiency does not protect from the development of diabetes

ObjectivesAdult subjects with untreated, lifetime, isolated GH deficiency (IGHD) due to a homozygous GHRH receptor gene mutation (MUT/MUT) residing in Itabaianinha, Brazil, present with lower BMI, higher prevalence of impaired glucose tolerance (IGT), increased insulin sensitivity (IS), and reduced β-cell function (βCF) when compared with non-BMI-matched homozygous normal controls. However, the prevalence of diabetes mellitus (DM) in this cohort is unknown. Comparing their IS and βCF with BMI-matched individuals heterozygous for the same mutation (MUT/N) may be useful to elucidate the role of the GH–IGF1 axis in IS and βCF. The purposes of this work were to verify the prevalence of IGT and DM in adult MUT/MUT subjects from this kindred and to compare IS and βCF in MUT/MUT and MUT/N.DesignCross-sectional study.MethodsWe studied most (51) of the living IGHD adults of this kindred who are GH naive. The oral glucose tolerance test (OGTT) could be performed in 34 subjects, fasting glucose was measured in 15, while two had a previous diagnosis of DM. The OGTT results of 24 MUT/MUT subjects were compared with those of 25 BMI-matched MUT/N subjects. IS was assessed by homeostatic model assessment of insulin resistance (HOMA–IR), quantitative IS check index, and oral glucose IS index for 2 and 3 h. βCF was assayed by HOMA-β, insulinogenic index, and the area under the curve of insulin:glucose ratio.ResultsThe prevalence of DM and IGT in IGHD was 15.68 and 38.23% respectively. IS was increased and βCF was reduced in MUT/MUT in comparison with MUT/N.ConclusionsLifetime, untreated IGHD increases IS, impairs βCF, and does not provide protection from diabetes.

Comparative effects of single-mode vs. duration-matched concurrent exercise training on body composition, low-grade inflammation, and glucose regulation in sedentary, overweight, middle-aged men

The effect of duration-matched concurrent exercise training (CET) (50% resistance (RET) and 50% endurance (EET) training) on physiological training outcomes in untrained middle-aged men remains to be elucidated. Forty-seven men (age, 48.1 ± 6.8 years; body mass index, 30.4 ± 4.1 kg·m(-2)) were randomized into 12-weeks of EET (40-60 min of cycling), RET (10 exercises; 3-4 sets × 8-10 repetitions), CET (50% serial completion of RET and EET), or control condition. The following were determined: intervention-based changes in fitness and strength; abdominal visceral adipose tissue (VAT), total body fat (TB-FM) and fat-free (TB-FFM) mass; plasma cytokines (C-reactive protein (CRP), tumor necrosis factor-α (TNFα) interleukin-6 (IL-6)); muscle protein content of p110α and glucose transporter 4 (GLUT4); mRNA expression of GLUT4, peroxisome proliferator-activated receptor-γ coactivator-1α-β, cytochrome c oxidase, hexokinase II, citrate synthase; oral glucose tolerance; and estimated insulin sensitivity. CET promoted commensurate improvements of aerobic capacity and muscular strength and reduced VAT and TB-FM equivalently to EET and RET (p < 0.05), yet only RET increased TB-FFM (p < 0.05). Although TNFα and IL-6 were reduced after all training interventions (p < 0.05), CRP remained unchanged (p > 0.05). EET reduced area under the curve for glucose, insulin, and C-peptide, whilst CET and RET respectively reduced insulin and C-peptide, and C-peptide only (p < 0.05). Notwithstanding increased insulin sensitivity index after all training interventions (p < 0.05), no change presented for GLUT4 or p110α total protein, or chronic mRNA expression of the studied mitochondrial genes (p > 0.05). In middle-aged men, 12 weeks of duration-matched CET promoted commensurate changes in fitness and strength, abdominal VAT, plasma cytokines and insulin sensitivity, and an equidistant glucose tolerance response to EET and RET; despite no change of measured muscle mechanisms associative to insulin action, glucose transport, and mitochondrial function.

Increased Insulin Sensitivity and Distorted Mitochondrial Adaptations during Muscle Unloading

We aimed to further investigate mitochondrial adaptations to muscle disuse and the consequent metabolic disorders. Male rats were submitted to hindlimb unloading (HU) for three weeks. Interestingly, HU increased insulin sensitivity index (ISI) and decreased blood level of triglyceride and insulin. In skeletal muscle, HU decreased expression of pyruvate dehydrogenase kinase 4 (PDK4) and its protein level in mitochondria. HU decreased mtDNA content and mitochondrial biogenesis biomarkers. Dynamin-related protein (Drp1) in mitochondria and Mfn2 mRNA level were decreased significantly by HU. Our findings provide more extensive insight into mitochondrial adaptations to muscle disuse, involving the shift of fuel utilization towards glucose, the decreased mitochondrial biogenesis and the distorted mitochondrial dynamics.

Oat β-Glucan Increased ATPases Activity and Energy Charge in Small Intestine of Rats

Dietary oat or oat products may potentially help to fight against high risk of cardiovascular diseases and β-glucan in oat was considered as a central player. The present study aimed to investigate the effects of dietary oat whole meal or β-glucan on insulin sensitivity and energy metabolism of rats. Rats were fed with control diet, oat whole meal based diet, or control diet with supplemented β-glucan for 4 weeks. Oat whole meal and β-glucan increased insulin sensitivity index. Interestingly, supplementation of oat whole meal or β-glucan induced increases in intestinal Na(+)K(+)-ATPase activity, Ca(2+)Mg(2+)-ATPase activity, and energy charge, particularly in the distal part of small intestine (ileum). Furthermore, amounts of Bifidobacterium and Lactobacillus in colon contents were elevated by oat whole meal or β-glucan. These findings provide an insight into that β-glucan increased insulin sensitivity and benefited intestinal health.

Antidiabetic Effect of the Total Polyphenolic Acids Fraction from Salvia miltiorrhiza Bunge in Diabetic Rats

An investigation was made to evaluate the therapeutic potential of the total polyphenolic acids fraction (PAF) from Salvia miltiorrhiza Bunge in the type 2 diabetes mellitus rats model with an oral dose of 187 mg/kg for 28 days. The results showed that PAF induced a significant decrease in fasting blood glucose (FBG), fasting blood insulin (FINS), total cholesterol (TC), triglyceride (TG) and blood urea nitrogen (BUN), and an obvious increase in insulin sensitivity index (ISI) in diabetic rats induced by a high fat diet and a low dose of streptozocin (STZ). These results suggested that PAF has antidiabetic potential in vivo.

ANTIHYPERGLYCEMIC EFFECT OF AQUEOUS EXTRACT OF SEA BUCKTHORN (HIPPOPHAE RHAMNOIDES L.) SEED RESIDUES IN STREPTOZOTOCIN-TREATED AND HIGH FAT-DIET-FED RATS

ABSTRACT The present study was designed to investigate the antihyperglycemic activity of the aqueous extract of sea buckthorn (Hippophae rhamnoides L.) seed residues (ASSR) in streptozotocin (STZ) and high-fat diet (HFD)-induced type 2 diabetic rats. Male Sprague-Dawley rats were divided into a normal control group (control), diabetic group and diabetic group supplemented with ASSR. Type 2 diabetes was induced by intravenous injection of low-dose STZ (25 mg/kg b.w.) and feeding with HFD for 10 weeks. Vehicle (distilled water) and ASSR (400 mg/kg b.w.) were orally administered once a day for 6 weeks. Our results showed that administration of ASSR significantly lowered the body weight, serum glucose, total cholesterol and low-density lipoprotein cholesterol levels in diabetic rats. Meanwhile, ASSR also significantly increased insulin sensitivity index in diabetic rats. These results suggest that ASSR might exhibit hypoglycemic and hypolipidemic effects in the STZ–HFD-induced type 2 diabetic rats. PRACTICAL APPLICATIONS Sea buckthorn (Hippophae rhamnoides L.) bush, bearing delicious and nutritious orange-colored berries, is locally called “Shaji” in China. The berry of sea buckthorn is one of the edible crude herbs that have been in use in Tibetan and Mongolian traditional medicines for a long time. In addition to medicinal use, the berries are processed into various products such as juice and marmalade, and are used for flavoring of dairy products. As a part of sea buckthorn berry, its seed is a by-product of the berry processing industry and also contains many bioactive substances. It was demonstrated in this study that ASSR was of hypoglycemic and hypolipidemic properties in experimental type 2-like diabetic rats. Therefore, seed residues of sea buckthorn and its aqueous extract could be added as supplement in health-care food or drugs or combined with other hypoglycemic drugs.

Diet and Exercise Interventions Reduce Intrahepatic Fat Content and Improve Insulin Sensitivity in Obese Older Adults

Both obesity and aging increase intrahepatic fat (IHF) content, which leads to nonalcoholic fatty liver disease (NAFLD) and metabolic abnormalities such as insulin resistance. We evaluated the effects of diet and diet in conjunction with exercise on IHF content and associated metabolic abnormalities in obese older adults. Eighteen obese (BMI >or=30 kg/m(2)) older (>or=65 years old) adults completed a 6-month clinical trial. Participants were randomized to diet (D group; n = 9) or diet + exercise (D+E group; n = 9). Primary outcome was IHF quantified by magnetic resonance spectroscopy (MRS). Secondary outcomes included insulin sensitivity (assessed by oral glucose tolerance), body composition (assessed by dual-energy X-ray absorptiometry), physical function (VO(2 peak) and strength), glucose, lipids, and blood pressure (BP). Body weight (D: -9 +/- 1%, D+E: -10 +/- 2%, both P < 0.05) and fat mass (D: -13 +/- 3%, D+E -16 +/- 3%, both P < 0.05) decreased in both groups but there was no difference between groups. IHF decreased to a similar extent in both groups (D: -46 +/- 11%, D+E: -45 +/- 8%, both P < 0.05), which was accompanied by comparable improvements in insulin sensitivity (D: 66 +/- 25%, D+E: 68 +/- 28%, both P < 0.05). The relative decreases in IHF correlated directly with relative increases in insulin sensitivity index (ISI) (r = -0.52; P < 0.05). Improvements in VO(2 peak), strength, plasma triglyceride (TG), and low-density lipoprotein-cholesterol concentration, and diastolic BP occurred in the D+E group (all P < 0.05) but not in the D group. Diet with or without exercise results in significant decreases in IHF content accompanied by considerable improvements in insulin sensitivity in obese older adults. The addition of exercise to diet therapy improves physical function and other obesity- and aging-related metabolic abnormalities.