Insulin Sensitivity In Rats Research Articles

Exercise Protects Against Defective Insulin Signaling and Insulin Resistance of Glucose Transport in Skeletal Muscle of Angiotensin II-Infused Rat.

Objectives: The present study investigated the impact of voluntary exercise on insulin-stimulated glucose transport and the protein expression and phosphorylation status of the signaling molecules known to be involved in the glucose transport process in the soleus muscle as well as other cardiometabolic risks in a rat model with insulin resistance syndrome induced by chronic angiotensin II (ANGII) infusion.Materials and Methods: Male Sprague-Dawley rats were assigned to sedentary or voluntary wheel running (VWR) groups. Following a 6-week period, rats in each group were subdivided and subcutaneously administered either normal saline or ANGII at 100 ng/kg/min for 14 days. Blood pressure, glucose tolerance, insulin-stimulated glucose transport and signaling proteins, including insulin receptor (IR), insulin receptor substrate 1 (IRS-1), Akt, Akt substrate of 160 kDa (AS160), AMPKα, c-Jun NH2-terminal kinase (JNK), p38 MAPK, angiotensin converting enzyme (ACE), ANGII type 1 receptor (AT1R), ACE2, Mas receptor (MasR) and oxidative stress marker in the soleus muscle, were evaluated.Results: Exercise protected against the insulin resistance of glucose transport and defective insulin signaling molecules in the soleus muscle; this effect was associated with a significant increase in AMPK Thr172 (43%) and decreases in oxidative stress marker (31%) and insulin-induced p38 MAPK Thr180/Tyr182 (45%) and SAPK/JNK Thr183/Tyr185 (25%), without significant changes in expression of AT1R, AT2R, ACE, ACE2, and MasR when compared to the sedentary rats given ANGII infusion. At the systemic level, VWR significantly decreased body weight, fat weight, and systolic blood pressure as well as improved serum lipid profiles.Conclusion: Voluntary exercise can alleviate insulin resistance of glucose transport and impaired insulin signaling molecules in the soleus muscle and improve whole-body insulin sensitivity in rats chronically administered with ANGII.

Combining Various Methods to Assess Insulin Sensitivity in Nonobese Rat after Sleeve Gastrectomy.

Sleeve gastrectomy (SG) procedure has been proved to improve insulin sensitivity and sustain anti-diabetic effects. Our aim is to co-use several methods to measure insulin sensitivity and investigate the effect of SG on hepatic and peripheral insulin sensitivity at early and long-term stages of postoperation. Thirty 11-week-old male Goto-Kakizaki rats were divided into SG, sham-operated SG (SOSG), and control groups. They were observed before operation and for 36 weeks of postoperation. Insulin tolerance test (ITT) and homeostasis model of assessment for insulin resistance index(HOMA-IR)were used to measure insulin resistance before operations and at 2 and 36 weeks of postoperation; Pyruvate challenge test (PCT) was administrated to assess the gluconeogenesis capability in order to reflect hepatic insulin sensitivity before operation and at 2 and 36 weeks of postoperation; Hyperinsulinemic euglycemic clamps (HIEC) was conducted before operation and at 2 and 36 weeks of postoperation to calculate the endogenous hepatic glucose production (HGP) at the basal and steady-state for evaluation of hepatic insulin sensitivity, and calculate the exogenous glucose infusion rate (GIR) at the steady-state for evaluation of peripheral insulin sensitivity. The data showed that compared with rats in the sham and control groups, rats in SG group had 1) significantly lower AUCITT, HOMA-IR and AUC PCT values at 2 and 36 weeks of postoperation, 2) lower basal state HGP, but not steady-state GIR at 2 weeks of postoperation, and 3) significantly different basal and steady-state HGP and steady-state GIR at 36 weeks of postoperation. In addition, the basal and steady-state HGP and the steady-state GIR were significantly different between rats in SG group at 2 and 36 weeks of postoperation. This study explored insulin sensitivity of rats after SG by jointly using a variety of techniques. The results showed that SG time-dependently improved the hepatic and peripheral insulin sensitivity.

Obesity Induced by High Fat Diet Impairs Glucose Tolerance and Insulin Sensitivity in Rats

Introduction: Obesity is a chronic disease, besides a risk factor for cardiovascular diseases, nowadays, it is characterized as a worldwide epidemic. The food imbalance and physical inactivity are factors that contribute to the emergence of obesity as well as diabetes. Objective: To evaluate the injury on glucose tolerance and insulin sensitivity in obese rats induced by high fat diet. Methodology: Male Rats Wistar (8 weeks old) were submitted to the standard diet (chow group, 11.8% kcal-Lipids; n = 5) and dietary intervention with high fat diet during 8 weeks (HFD group, 58.4% kcal-Lipids; n= 5). It was evaluated the body weight weekly, and fasting and fed blood glucose. At the end of the experimental period, was measured the glucose tolerance, insulin sensitivity and gluconeogenesis. After the animal sacrifice, it was analyzed relative weight of white adipose tissue, as well as the adipocytes diameter (epididymal white adipose tissue) and circulating levels of leptin. Results and Discussion: The group HFD presented higher body weight (from the 2nd week of diet), an increase accumulation of epididymal and perirenal white adipose tissue. In addition, in these animals, it was observed a significant increase in the adipocytes diameter and the levels of leptin in plasma when compared to animals chow, indicating obesity with increased release of cytokines. In HFD group, the fasting blood glucose levels were significantly higher in the 6th week of high fat diet consumption compared to the chow group. Adding up to the frame of obesity, at the end of the 8th week of high fat diet consumption, the obese group had higher fasting plasma glucose in fed state, glucose intolerance, insulin resistance, as well as increased gluconeogenesis as compared with the chow group. Conclusion: Obesity with adipocyte hypertrophy, induced by high fat diet, induces glycemic damages, as the elevation of blood glucose, glucose intolerance and lower insulin sensitivity in rats.

Melatonin Receptor Agonist Piromelatine Ameliorates Impaired Glucose Metabolism in Chronically Stressed Rats Fed a High-Fat Diet.

Modern lifestyle factors (high-caloric food rich in fat) and daily chronic stress are important risk factors for metabolic disturbances. Increased hypothalamic-pituitary-adrenal (HPA) axis activity and the subsequent excess production of glucocorticoids (GCs) in response to chronic stress (CS) leads to increases in metabolic complications, such as type 2 diabetes and insulin resistance (IR). Melatonin (MLT), which protects several regulatory components of the HPA axis from GC-induced deterioration, might improve glucose homeostasis. Piromelatine is a melatonin receptor-1/melatonin receptor-2 (MT1/MT2) agonist with high affinity for MLT receptors and a longer duration of action than MLT. The objective of the present study was to explore the potential effects of piromelatine on glucose and lipid metabolism and insulin sensitivity in rats with IR induced by a high-fat diet combined with CS (CF). The results showed that piromelatine prevented the suppression of body weight gain and energy intake induced by CF and normalized CF-induced hyperglycemia and homeostasis model assessment-IR index, which suggests that piromelatine prevented whole-body IR. Piromelatine also prevented CF-induced dysregulation of genes involved in glucose and lipid metabolism, including proinflammatory cytokines, in adipose tissue. In addition, piromelatine also attenuated CF-induced excess free corticosterone release, increased glucocorticoid receptor expression, and decreased 11β-hydroxysteroid dehydrogenase-1 expression, suggesting that piromelatine might ameliorate impaired glucose metabolism and prevent IR by normalizing HPA-axis functions. In conclusion, piromelatine might be a novel therapeutic agent for glucose intolerance and IR.

Heat-killed Bifidobacterium animalis subsp. Lactis CECT 8145 increases lean mass and ameliorates metabolic syndrome in cafeteria-fed obese rats

To evaluate the ability of the heat-killed probiotic Bifidobacterium animalis subsp. lactis CECT 8145 (Ba8145) to ameliorate Metabolic Syndrome (MetS), four groups of male Wistar rats were fed either standard chow (ST) or the obesogenic cafeteria diet (CAF) and were orally supplemented with either heat-killed Ba8145 (1010 CFU/day) (ST-Ba8145 and CAF-Ba8145 groups) or vehicle (ST-veh and CAF-veh groups) for 84days. Both ST-Ba8145 and CAF-Ba8145 rats displayed increased energy expenditure (EE) and a decrease of relative mesenteric white adipose tissue (MWAT%). CAF-BA8145 animals showed decreased cumulative energy intake, increased relative lean mass, higher insulin sensitivity, elevated gene expression of adipose triacylglycerol lipase and fatty acid transporter 1 in MWAT and lower circulating levels of non-esterified free fatty acids, LDL/VLDL cholesterol and triacylglycerols than CAF-veh rats. In conclusion, heat-killed Ba8145 intake ameliorates mesenteric adiposity and dyslipidaemia, increases EE and lean mass and improves insulin sensitivity in rats induced to MetS.

Antihyperglycemic Effect of Rosa Damascena is Mediated by PPAR.γ Gene Expression in Animal Model of Insulin Resistance.

Insulin resistance is a condition in which insulin signaling and action are impaired in insulin sensitive tissues and result in hyperglycemia, hyperlipidemia, and type 2 diabetes mellitus. Our previous studies have shown that Rosa damascena has antihyperglycemic effects on diabetic and normal rats. Therefore, we conducted a study to evaluate the effect of this medicinal plant on insulin sensitivity in rats. This study was performed on high fructose diet insulin resistant rats and pioglitazone, an insulin sensitizing drug, was used as a positive control. Insulin resistance was developed in animals by high fructose diet within six weeks. Then, Rosa damascena extract and pioglitazone were administered by gavage for two weeks and results were compared with two control groups. After treatment period, serum glucose, insulin, adiponectin, triglyceride, and cholesterol were assayed in fasting state. Plasma free fatty acid profile was analyzed by GC. Liver PPAR.γ and muscle GLUT.4 gene expressions were assessed by real time PCR and western blotting. Animals were treated with rosa damascena extract showed levels of insulin (42 ± 2.7 pmol/L). adiponectin (5.6±0.17 μg/mL). glucose (129±4.7 mg/dL). and triglyceride (75 ± 9 mg/dl) which were significantly improved as compared with control group insulin (137 ± 34 pmol/L), adiponectin (3.9±0.15 μg/mL). glucose (187±15 mg/dL). and triglycerides (217±18 mg/dL). PPARγ protein level was also significantly increased in Rosa damascene treated group. Our results demonstrated that rosa damascena extract has useful effects on insulin resistant animals and by increasing insulin sensitivity can be considered as a potential agent in control of diabetes.

Swimming training induces liver adaptations to oxidative stress and insulin sensitivity in rats submitted to high-fat diet

ABSTRACTOxidative stress, physical inactivity and high-fat (FAT) diets are associated with hepatic disorders such as metabolic syndrome (MS). The therapeutic effects of physical training (PT) were evaluated in rats with MS induced by FAT diet for 13 weeks, on oxidative stress and insulin signaling in the liver, during the last 6 weeks. FAT-sedentary (SED) rats increased body mass, retroperitoneal fat, mean arterial pressure (MAP) and heart rate (HR), and total cholesterol, serum alanine aminotransferase, glucose and insulin. Livers of FAT-SED rats increased superoxide dismutase activity, thiobarbituric acid-reactive substances, protein carbonyl and oxidized glutathione (GSSG); and decreased catalase activity, reduced glutathione/GSSG ratio, and the mRNA expression of insulin receptor substrate 1 (IRS-1) and serine/threonine kinase 2. FAT-PT rats improved in fitness and reduced their body mass, retroperitoneal fat, and glucose, insulin, total cholesterol, MAP and HR; and their livers increased superoxide dismutase and catalase activities, the reduced glutathione/GSSG ratio and the expression of peroxisome proliferator-activated receptor gamma and insulin receptor compared to FAT-SED rats. These findings indicated adaptive responses to PT by restoring the oxidative balance and insulin signaling in the liver and certain biometric and biochemical parameters as well as MAP in MS rats.

Consumption of guava may have beneficial effects in type 2 diabetes: A bioactive perspective

The objectives of this study were to evaluate the anti-diabetic and anti-hyperlipidemic effects and relative mechanisms of guava polysaccharides (GPs) in rats with type 2 diabetic mellitus (T2DM). The chemical characterization and monosaccharide compositions of GPs, named as GP-1, GP-2, GP-3, and GP-4, were determined by PMP-HPLC and FT-IR. The results revealed that all GPs had the typical saccharide absorptions, and all were heteropolysaccharides. In addition, GPs efficiently decreased levels of fasting blood glucose, glucosylated serum protein, serum insulin, homeostasis model assessment of insulin resistance, total cholesterol, triglyceride and serum alanine transaminase, improved oral glucose tolerance, and increased insulin sensitivity in rats with T2DM. Histopathological observations suggested that GP-1, GP-3, and GP-4 could alleviate injury in pancreatic islet cells, and Western blot analysis showed that these GPs upregulated gene expression of the insulin receptor, insulin receptor substrate 2, Akt, and glucose transporter type 4. Taken together, these data suggest that GPs may be beneficial in treating T2DM and reducing the risk of hyperlipidemia, vascular disease, and cirrhosis via the PI3K/Akt signaling pathway.

Of the milk sugars, galactose, but not prebiotic galacto-oligosaccharide, improves insulin sensitivity in male Sprague-Dawley rats.

BackgroundConsumption of dairy products reduces risk of type 2 diabetes. Milk proteins and fats exhibit anti-diabetic properties but milk sugars have been studied little in this context. Galactose from milk lactose is readily converted to glycogen in the liver but its effects on insulin sensitivity have not been assessed. Prebiotic oligosaccharides from milk alter gut microbiota and can thereby influence host metabolism. Our objective was to assess the effect on insulin sensitivity of dietary galactose compared to glucose and fructose, and fermentable galacto-oligosaccharides compared to non-fermentable methylcellulose.MethodsDiets containing 15% of dry matter from glucose, fructose, galactose, galacto-oligosaccharides, or methylcellulose were fed to 36 rats per diet for 9 weeks. Hyperinsulinemic-euglycemic clamps with [3-3H]glucose infusion and a steady-state 2-[1-14C]deoxyglucose bolus injection were used to assess insulin sensitivity and glucose uptake indices. Tissue was collected in fed, fasted and fasted, insulin-stimulated states.ResultsGalactose increased glucose infusion rate during the clamp by 53% and decreased endogenous glucose production by 57% compared to glucose and fructose. Fed-state hepatic glycogen content was greater with galactose compared to glucose and fructose, consistent with a potentiation of the insulin effect on glycogen synthase by dephosphorylation. Galactose decreased the fecal Firmicutes:Bacteroidetes ratio while galacto-oligosaccharides increased abundance of fecal Bifidobacterium spp. 481-fold compared to methylcellulose, and also increased abundance of Lactobacillus spp. and Bacteroidetes. Galacto-oligosaccharides did not affect glucose infusion rate or endogenous glucose production during basal or clamp periods compared to methylcellulose.ConclusionsGalactose at 15% of daily intake improved hepatic insulin sensitivity in rats compared to glucose and fructose. Galactose caused an increase in fed-state hepatic glycogen content and a favourable shift in gut microbial populations. Intake of galacto-oligosaccharides improved the gut microbial profile but did not improve insulin sensitivity.

Supranutritional selenium intake from enriched milk casein impairs hepatic insulin sensitivity via attenuated IRS/PI3K/AKT signaling and decreased PGC-1α expression in male Sprague–Dawley rats

Selenium (Se)-enriched milk provides antioxidant benefits and has therapeutic potential against cancer. However, both antidiabetic and prodiabetic effects have been attributed to Se. Our objective was to evaluate the effect of Se-enriched milk casein on insulin sensitivity in rats when given at the requirement of 0.25 ppm Se and supranutritionally on both low- and high-fat diets. Two hundred sixteen male Sprague–Dawley rats were fed low- or high-fat diets containing one, two or eight times the Se requirement in a randomized block design. After 7 weeks, 72 rats were subjected to the hyperinsulinemic–euglycemic clamp with [3-3H]glucose infusion to estimate glucose fluxes. Tissues were collected from the remaining 144 rats 8 min after ip saline or insulin injection. During hyperinsulinemic–euglycemic clamps, glucose infusion rate was 22% lower (P=.058), and endogenous glucose production was 76% higher (P=.054) when Se content increased from one to eight times the requirement on low-fat diets, indicating impaired hepatic insulin sensitivity. Se also decreased the ability for insulin to stimulate Akt phosphorylation at Thr308. Hepatic oxidation state and expression of selenoprotein P and glutathione peroxidase-1 were unaffected while expression of insulin receptor substrate (IRS)-1 and−2 and PPARγ coactivator-1α (PGC-1α) decreased with supranutritional Se and high-fat intake. In addition, hepatic expression of regulatory and catalytic subunits of phosphatidylinositol 3-kinase (PI3K) decreased with supranutritional intake of Se. Se intake from enriched casein up to eight times the requirement impairs hepatic insulin sensitivity in a mechanism similar to fat feeding, via attenuated IRS/PI3K/Akt signaling and decreased PGC-1α expression.

Docosapentaenoic acid and docosahexaenoic acid are positively associated with insulin sensitivity in rats fed high-fat and high-fructose diets.

The aim of the present study was to compare insulin resistance and metabolic changes using a global lipidomic approach. Rats were fed a high-fat diet (HFD) or a high-fructose diet (HFrD) for 12 weeks to induce insulin resistance (IR) syndrome. After 12 weeks feeding, physiological and biochemical parameters were examined. Insulin sensitivity and plasma metabolites were evaluated using a euglycemic-hyperinsulinemic clamp and mass spectrometry, respectively. Pearson's correlation coefficient was used to investigate the strength of correlations. Rats on both diets developed IR syndrome, characterized by hypertension, hyperlipidemia, hyperinsulinemia, impaired fasting glucose, and IR. Compared with HFrD-fed rats, non-esterified fatty acids were lower and body weight and plasma insulin levels were markedly higher in HFD-fed rats. Adiposity and plasma leptin levels were increased in both groups. However, the size of adipocytes was greater in HFD- than HFrD-fed rats. Notably, the lipidomic heat map revealed metabolites exhibiting greater differences in HFD- and HFrD-fed rats compared with controls. Plasma adrenic acid levels were higher in HFD- than HFrD-fed rats. Nevertheless, linoleic and arachidonic acid levels decreased in HFrD-fed rats compared with controls. Plasma concentrations of docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) were significantly reduced after feeding of both diets, particularly the HFrD. There was a strong positive correlation between these two fatty acids and the insulin sensitivity index. The systemic lipidomic analysis indicated that a reduction in DHA and DPA was strongly correlated with IR in rats under long-term overnutrition. These results provide a potential therapeutic target for IR and metabolic syndrome.

Differential effects of hypercaloric choice diets on insulin sensitivity in rats.

We showed previously that rats on a free-choice high-fat, high-sugar (fcHFHS) diet become rapidly obese and develop glucose intolerance within a week. Interestingly, neither rats on a free-choice high-fat diet (fcHF), although equally obese and hyperphagic, nor rats on a free-choice high-sugar (fcHS) diet consuming more sugar water, develop glucose intolerance. Here, we investigate whether changes in insulin sensitivity contribute to the observed glucose intolerance and whether this is related to consumption of saturated fat and/or sugar water. Rats received either a fcHFHS, fcHF, fcHS or chow diet for one week. We performed a hyperinsulinemic-euglycemic clamp with stable isotope dilution to measure endogenous glucose production (EGP; hepatic insulin sensitivity) and glucose disappearance (Rd; peripheral insulin sensitivity). Rats on all free-choice diets were hyperphagic, but only fcHFHS-fed rats showed significantly increased adiposity. EGP suppression by hyperinsulinemia in fcHF-fed and fcHFHS-fed rats was significantly decreased compared with chow-fed rats. One week fcHFHS diet also significantly decreased Rd. Neither EGP suppression nor Rd was affected in fcHS-fed rats. Our results imply that, short-term fat feeding impaired hepatic insulin sensitivity, whereas short-term consumption of both saturated fat and sugar water impaired hepatic and peripheral insulin sensitivity. The latter likely contributed to glucose intolerance observed previously. In contrast, overconsumption of only sugar water affected insulin sensitivity slightly, but not significantly, in spite of similar adiposity as fcHF-fed rats and higher sugar intake compared with fcHFHS-fed rats. These data imply that the palatable component consumed plays a role in the development of site-specific insulin sensitivity.

Regulation of glucose dynamics by noninvasive peripheral electrical stimulation in normal and insulin-resistant rats

BackgroundThe epidemic nature of type 2 diabetes mellitus (T2DM), along with the downsides of current treatments, has raised the need for therapeutic alternatives. MethodsWe studied normo-glycemic and high-fat diet (HFD), induced insulin-resistant Wistar Han rats for 2 to 3weeks. Rats received peripheral electrical stimulation (PES) treatment (2Hz/16Hz bursts, 10mA) in their hind limbs for 3min, 3 times per week. Glucose tolerance was evaluated by using a glucose tolerance test at the beginning and again at the end of the study. The effect of an acute PES treatment on metabolic rates of glucose appearance and turnover was measured by using the hyperinsulinemic–euglycemic clamp (HEGC) test. ResultsRepeated PES treatment significantly inhibited the progression of glucose intolerance in normal and insulin-resistant rats and prevented HFD-induced gains in body weight and fat mass. Acute treatment induced a prolonged effect on glucose turnover, as evaluated by the HEGC test. Increased hepatic glucose output was observed during the basal state (P<0.005). Under hyperinsulinemic conditions, PES improved tissue sensitivity to insulin (41.1%, P<0.01), improved suppression of hepatic glucose production (58.9±4.4% vs. 87.1±4.4%, P<0.02) and significantly elevated the rate of glycogenesis (P<0.01), compared with controls. ConclusionsThe present study indicates that a noninvasive PES treatment of very short duration is sufficiently potent to stimulate glucose utilization and improve hepatic insulin sensitivity in rats. Repeated PES treatment may have a beneficial effect on HFD-induced adiposity and control of body weight.

7-week aerobic exercise training reduces adipocyte area and improves insulin sensitivity in Wistar rats fed a highly palatable diet

The aim of this study was to evaluate the effect aerobic exercise training on fat pad mass, adipocyte size, leptin release and insulin sensitivity in rats fed with high fat-palatable diet. Twenty-four male Wistar rats (250-260g) were divided into four groups: sedentary control (CTR/SD), trained control (CTR/TR), obese sedentary (OB/SD) and obese trained (OB/TR). Obese groups were fed with high fat-palatable diet (27% of fat) and control groups fed with AIN-93. Our results showed that aerobic exercise training was effective to reduce body weight and epididymal fat mass in CTR/TR and OB/TR. Insulin and glucose levels were increased in OB/TR compared with OB/SD. Aerobic exercise training reduced the average area of adipocytes in CTR/TR and OB/TR and it was associated with reduced plasma insulin and leptin. In conclusion, 7-week aerobic exercise training reduces adipocyte area and improves insulin sensitivity and leptin levels in high fat-palatable diet-fed Wistar rats.

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 Crucial Role of C18-Cer in Fat-Induced Skeletal Muscle Insulin Resistance

Background/Aims: Muscle bioactive lipids accumulation leads to several disorder states. The most common are insulin resistance (IR) and type 2 diabetes. There is an ongoing debate which of the lipid species plays the major role in induction of muscle IR. Our aim was to elucidate the role of particular lipid group in induction of muscle IR. Methods: The analyses were performed on muscle from the following groups of rats: 1. Control, fed standard diet, 2 HFD, fed high fat diet, 3. HFD/Myr, fed HFD and treated with myriocin (Myr), an inhibitor of ceramide de novo synthesis. We utilized [U¹³C] palmitate isotope tracer infusion and mass spectrometry to measure content and synthesis rate of muscle long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramide (Cer). Results: HFD led to intramuscular accumulation of LCACoA, DAG and Cer and skeletal muscle IR. Myr-treatment caused decrease in Cer (most noticeable for stearoyl-Cer and oleoyl-Cer) and accumulation of DAG, possibly due to re-channeling of excess of intramuscular LCACoA towards DAG synthesis. An improvement in insulin sensitivity at both systemic and muscular level coincided with decrease in ceramide, despite elevated intramuscular DAG. Conclusion: The improved insulin sensitivity was associated with decreased muscle stearoyl- and oleoyl-ceramide content. The results indicate that accumulation of those ceramide species has the greatest impact on skeletal muscle insulin sensitivity in rats.

Effects of Growth Hormone on Diurnal Insulin Sensitivity in Normal and Type 2 Diabetic Patients and Animal Models

This review addresses the effects of growth hormone on diurnal insulin sensitivity in normal, patients with type 2 diabetes mellitus (T2DM) and animal models described in our previous studies. Results confirmed the presence of diurnal insulin sensitivity, or greater insulin sensitivity in the morning, in normal subjects. The exact cause of this circadian rhythm in plasma glucose levels in healthy subjects has not been established, and nocturnal surges in growth hormone secretion remain a possible explanation. Results showed that growth hormone is an important factor controlling the diurnal variation of glucose tolerance and insulin sensitivity in rats. Data from our previous study provided direct evidence that the role of growth hormone in regulating insulin sensitivity in healthy subjects may be related to changes in the metabolic clearance rate of insulin and the metabolism of non-esterified fatty acids. A different circadian rhythm for plasma glucose appears to be present in patients with T2DM with nadirs in the early evening and peaks in the early morning, indicating greater insulin sensitivity in the evening. As in normal subjects, the exact cause of these circadian rhythms in the plasma glucose levels of patients with T2DM provided direct evidence that the reduction in insulin sensitivity may be due to the nocturnal surge of growth hormone in the early morning hours.

The effect of L-arginine and ascorbic acid on the visceral fat and the concentrations of metalloproteinases 2 and 9 in high-fat-diet rats.

L-arginine (L-arg) and vitamin C supplementation may decrease fat accumulation and have a favourable effect on carbohydrate metabolism. This is partly caused by matrix metalloproteinases (MMPs), which are involved in adipocyte development and remodelling. Our study evaluated the effects of L-arg and vitamin C supplementation on the content of visceral fat (VF%), activity of MMPs, and insulin resistance (IR) in rats fed a high-fat diet (HFD). The experiment was performed using 48 Wistar rats divided into four groups: Group 1 was fed a standard diet, Group 2 a HFD, Group 3 a HFD supplemented with L-arg (A), and Group 4 a HFD supplemented with L-arg and vitamin C (AC). The animals were euthanized after six weeks. The concentrations of serum glucose, insulin, MMP-2, and MMP-9, as well as IR by Homeostatic Model Assessment (HOMA) and VF% were measured. Statistically significant increases in VF%, MMP-2, MMP-9, insulin, and HOMA-IR levels were observed in the HFD group when compared to the control group. A smaller increase in VF%, insulin, and HOMA-IR was seen in Group 3 (A) and 4 (AC). L-arg supplementation protected against increases in MMP-2 and MMP-9 in Group 3 (A) and 4 (AC). L-arginine could protect from an increase in visceral fat through a change in the activity of MMPs and amelioration of insulin sensitivity in rats fed a HFD. The addition of vitamin C did not improve the effects of L-arginine supplementation.

Colonic Fermentation of Unavailable Carbohydrates from Unripe Banana and its Influence over Glycemic Control.

The aim of this study was to evaluate the effect of the colonic fermentation of unavailable carbohydrates from unripe banana (mass - UBM - and starch - UBS) over parameters related to glucose and insulin response in rats. Wistar male rats were fed either a control diet, a UBM diet (5 % resistant starch - RS) or a UBS diet (10 % RS) for 28 days. In vivo (oral glucose tolerance test) and in vitro (cecum fecal fermentation, pancreatic islet insulin secretion) analyses were performed. The consumption of UBM and UBS diets by Wistar rats for 28 days improved insulin/glucose ratio. Also, pancreatic islets isolated from the test groups presented significant lower insulin secretion compared to the control group, when the same in vitro glucose stimulation was done. Total short chain fatty acids produced were higher in both experimental groups in relation to the control group. These findings suggest that UBM and UBS diets promote colonic fermentation and can influence glycemic control, improving insulin sensitivity in rats.

Supplementing diet with blackberry extract causes a catabolic response with increments in insulin sensitivity in rats.

Blackberry (Rubus sp.) fruit has a high content of anthocyanins, but its health benefits have not been sufficiently explored in healthy individuals. Thus, the aim of the study was to determine the effects of blackberry extract on lipid and glucose variables in female and male rats. Sprague Dawley rats were given a standard pellet (SD) or cafeteria (CD) diet supplemented (SD+R and CD+R) or not with Rubus extract for 80 days. Female rats given SD+R had lower body and liver weights than SD females; both sexes given SD+R showed lower plasma glucose and insulin, higher plasma NEFA, glycerol and 3-hydroxybutyrate, and higher liver concentration of triacylglycerols than SD rats. The homeostasis model of insulin resistance (HOMA) was lower in SD+R rats than in SD rats, but higher in CD rats. No effects of Rubus extract were observed in CD rats. In conclusion, Rubus extract, in rats given SD, decreased glycemia and increased insulin sensitivity. It also increased lipid breakdown in adipose tissue. The effects were greater in females than in males. No effect was seen in rats given CD, probably as a result of their high insulin resistance.