Rat Model Of Insulin Resistance Research Articles

Chromium Picolinate and Rosiglitazone Improve Biochemical Derangement in a Rat Model of Insulin Resistance: Role of TNF-a and Leptin

Chromium Picolinate and Rosiglitazone Improve Biochemical Derangement in a Rat Model of Insulin Resistance: Role of TNF-a and Leptin

Supplementation ofLactobacillus plantarumK68 and Fruit-Vegetable Ferment along with High Fat-Fructose Diet Attenuates Metabolic Syndrome in Rats with Insulin Resistance

Lactobacillus plantarum K68 (isolated from fu-tsai) and fruit-vegetable ferment (FVF) have been tested for antidiabetic, anti-inflammatory, and antioxidant properties in a rat model of insulin resistance, induced by chronic high fat-fructose diet. Fifty rats were equally assigned into control (CON), high fat-fructose diet (HFFD), HFFD plus K68, HFFD plus FVF, and HFFD plus both K68 and FVF (MIX) groups. Respective groups were orally administered with K68 (1 × 109 CFU/0.5 mL) or FVF (180 mg/kg) or MIX for 8 weeks. We found that HFFD-induced increased bodyweights were prevented, and progressively increased fasting blood glucose and insulin levels were reversed (P < 0.01) by K68 and FVF treatments. Elevated glycated hemoglobin (HbA1c) and HOMA-IR values were controlled in supplemented groups. Furthermore, dyslipidemia, characterized by elevated total cholesterol (TC), triglyceride (TG), and low-density lipoproteins (LDLs) with HFFD, was significantly (P < 0.01) attenuated with MIX. Elevated pro-inflammatory cytokines, interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), were controlled (P < 0.01) by K68, FVF, and MIX treatments. Moreover, decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were substantially (P < 0.01) restored by all treatments. Experimental evidences demonstrate that K68 and FVF may be effective alternative medicine to prevent HFFD-induced hyperglycemia, hyperinsulinemia, and hyperlipidemia, possibly associated with anti-inflammatory and antioxidant efficacies.

Comparison of Tissue Metal Concentrations in Zucker Lean, Zucker Obese, and Zucker Diabetic Fatty Rats and the Effects of Chromium Supplementation on Tissue Metal Concentrations

Diabetes results in several metabolic changes, including alterations in the transport, distribution, excretion, and accumulation of metals. While changes have been examined in several rat models of insulin resistance and diabetes, the metal ion concentrations in the tissues of Zucker lean, Zucker obese (an insulin resistance and early stage diabetes model), and Zucker diabetic fatty (ZDF, a type 2 diabetes model) have not previously been examined in detail. The concentration of Cu, Zn, Fe, Mg, and Ca were examined in the liver, kidney, heart and spleen, and Cr concentration in the liver and kidney of these rats were examined. Zucker obese rats have a reduction in the concentration of Cu, Zn, Fe, Mg in the liver compared to ZDF and/or lean Zucker rats, presumably as a result of the increased fat content of the liver of the obese rats. ZDF rats have increased concentrations of kidney Cu compared to the lean rats, while kidney Ca concentrations are increased in the Zucker obese rats. Spleen Fe concentrations are decreased in Zucker obese rats compared to the lean rats. No effects on metal concentrations in the heart were observed between the lean, obese, and ZDF rats, and no effects on Cr concentrations were identified. Cr(III) complexes have previously been shown to have beneficial effects on the signs of insulin resistance in Zucker obese and ZDF rats. The effects of daily gavage administration of chromium picolinate ([Cr(pic)(3)]) (1 mg Cr/kg body mass), CrCl(3) (1 mg Cr/kg body mass), and Cr3 ([Cr(3)O(propionate)(6)(H(2)O)(3)](+)) (33 μg and 1 mg Cr/kg body mass) on metal concentrations in these tissues were examined. Treatment with CrCl(3) and Cr3, but not [Cr(pic)(3)], at 1 mg Cr/kg resulted in a statistically significant accumulation of Cr in the kidney of lean and obese but not ZDF rats but resulted in lowering the elevated levels of kidney Cu in ZDF rats, suggesting a beneficial effect on this symptom of type 2 diabetes.

Antiobesity actions of Embelia ribes

Embelia ribes has been used as a folk medicine whole world. An aqueous extract of Embelia ribes have visceral fat accumulation and improved insulin resistance in rat model with HFD induced obesity may possibly be through down regulation of leptin, TNF-α, SREBP1γ, and PPARγ2 gene expression. The leptin might contribute to hepatic steatosis by promoting insulin resistance and also by altering insulin signaling in hepatocytes, which consequently promote increased intracellular fatty acid. Hence, drug treatment to rats with HFD prevents increase of these levels due to decrease of the body fat content. Therefore we investigated the anti-obesity effects of the aqueous extract of Embelia ribes by feeding a high-fat diet to rats for 42 weeks. Body weights at 2-6 weeks and parametrial adipose tissue weights were significantly lower in rat fed the high-fat diet containing aqueous extract of Embelia ribes than in the controls fed the high-fat diet. Our data suggest that the antiobesity effects of aqueous extract of Embelia ribes in rat fed a high-fat diet may be through down regulation of leptin, TNF-α, SREBP1γ, and PPARγ2 gene expression.

Effects of metformin on insulin resistance in heart failure. Which came first: the chicken or the egg?

Effects of metformin on insulin resistance in heart failure. Which came first: the chicken or the egg?

ISP27: Omega 3 PUFA chain length: a key factor of their efficiency on cardiovascular risk factors in experimental metabolic syndrome

Background and aims The impact of dietary n-3 polyunsaturated fatty acids (PUFA), on cardiometabolic risk prevention was evaluated according to chain length, in two rat models of non-obese insulin resistance and hypertension. Materials and Methods Fructose-fed rat was used as a model of acquired metabolic syndrome (MS) and spontaneously hypertensive rat (SHR) rat as a model of inherited MS. The rats were submitted to a diet containing either no n-3 PUFAs (control) or α-linolenic acid (ALA) as single n-3 PUFA source or a mix of ALA and its two main longer chain metabolites (LC), eicosapentaenoic and docosahexaenoic acids. During the dietary period, glucose and insulin tolerance tests were performed and serum triglycerides concentration was quantified. Arterial blood pressure was evaluated punctually by tail-cuff or continuously by implanted telemetry. After 10 weeks of feeding, the fatty acid (FA) composition of insulin-sensitive tissues was analysed. Results The 2 experimental models developed insulin resistance and hypertension, associated to an alteration of the specific FA pattern in insulin sensitive tissues. Insulin resistance was also associated to a high cardiovascular risk as evaluated by the increase in blood pressure parameters and especially by the increase in pulse pressure in the fructose-fed rats. LC n-3 PUFA significantly affected the development of insulin resistance, impaired glucose tolerance, blood pressure rise and hypertriglyceridemia, in relation with a strong limitation of the FA composition in the insulin sensitive tissue phospholipids. Conversely, ALA alone affected only hypertriglyceridemia. Conclusion Whatever the etiology of insulin resistance, the significant beneficial effects of n-3 PUFAs on the prevention of cardiometabolic risk factors can be attributed to the long chain n-3 PUFAs but not to the precursor.

Dietary chia seed induced changes in hepatic transcription factors and their target lipogenic and oxidative enzyme activities in dyslipidaemic insulin-resistant rats

The present study analyses the effect of dietary chia seed rich in n-3 α-linolenic acid on the mechanisms underlying dyslipidaemia and liver steatosis developed in rats fed a sucrose-rich diet (SRD) for either 3 weeks or 5 months. The key hepatic enzyme activities such as fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), glucose-6-phosphate dehydrogenase (G-6-PDH), carnitine palmitoyltransferase-1 (CPT-1) and fatty acid oxidase (FAO) involved in lipid metabolism and the protein mass levels of sterol regulatory element-binding protein-1 (SREBP-1) and PPARα were studied. (1) For 3 weeks, Wistar rats were fed either a SRD with 11 % of maize oil (MO) as dietary fat or a SRD in which chia seed replaced MO (SRD+Chia). (2) A second group of rats were fed a SRD for 3 months. Afterwards, half the rats continued with the SRD while for the other half, MO was replaced by chia for 2 months (SRD+Chia). In a control group, maize starch replaced sucrose. Liver TAG and the aforementioned parameters were analysed in all groups. The replacement of MO by chia in the SRD prevented (3 weeks) or improved/normalised (5 months) increases in dyslipidaemia, liver TAG, FAS, ACC and G-6-PDH activities, and increased FAO and CPT-1 activities. Protein levels of PPARα increased, and the increased mature form of SREBP-1 protein levels in the SRD was normalised by chia in both protocols (1 and 2). The present study provides new data regarding some key mechanisms related to the fate of hepatic fatty acid metabolism that seem to be involved in the effect of dietary chia seed in preventing and normalising/improving dyslipidaemia and liver steatosis in an insulin-resistant rat model.

Suppression of Vascular Inflammation by Kinin B1 Receptor Antagonism in a Rat Model of Insulin Resistance

Kinin B1 receptor (B1R) intervenes in a positive feedback loop to amplify and perpetuate the vascular oxidative stress in glucose-fed rats, a model of insulin resistance. This study aims at determining whether B1R blockade could reverse vascular inflammation in this model. Young male Sprague-Dawley rats were fed with 10% D-glucose or tap water (controls) for 8 weeks, and during the last week, rats were administered the B1R antagonist SSR240612 (10 mg/kg/day, gavage) or the vehicle. The outcome was determined on glycemia, insulinemia, insulin resistance (homeostasis model assessment index), and on protein or mRNA expression of the following target genes in the aorta (by Western blot and real-time quantitative polymerase chain reaction): B1R, endothelial nitric oxide synthase, inducible nitric oxide synthase, macrophage CD68, macrophage/monocyte CD11b, interleukin (IL) -1β, tumor necrosis factor-α, IL-6, macrophage migration inhibitory factor, intercellular adhesion molecule-1, and E-selectin (endothelial adhesion molecule). Data showed increased expression of all these markers in the aorta of glucose-fed rats except endothelial nitric oxide synthase and tumor necrosis factor-α, which were not affected. SSR240612 reversed hyperglycemia, hyperinsulinemia, insulin resistance, and the upregulation of B1R, inducible nitric oxide synthase, macrophage CD68, and CD11b, IL-1β, inter-cellular adhesion molecule-1, macrophage migration inhibitory factor, and E-selectin in glucose-fed rats, yet it had no significant effect on IL-6 and in control rats. Kinin B1R antagonism reversed the upregulation of its own receptor and several pro-inflammatory markers in the aorta of glucose-fed rats. These data provide the first evidence that B1R may contribute to the low-grade vascular inflammation in insulin resistance, an early event in the development of type-2 diabetes.

Therapeutic Effect of Carboxymethylated and Quanternized Chitosan on Insulin Resistance in High-Fat-Diet-Induced Rats and 3T3-L1 Adipocytes

Owing to their distinct biochemical properties, chitosan and its derivatives have a great potential in a range of bioapplications. One such application is as a dietary antilipidemic supplement to be used in reducing obesity and to improve insulin resistance. The lipid-binding efficiency of chitosan and its derivatives, however, remains debatable. Accordingly, in this study we investigated the interaction of chitosan and its two derivatives, O-carboxymethyl chitosan (O-CMCs) and N-[(2-hydroxy-3-N,N-dimethylhexadecyl ammonium)propyl]chitosan chloride (N-CQCs), with plasma leptin, glucose, insulin and total cholesterol in a diet-induced insulin-resistant rat model, and further interaction with mRNA expression of adipocytokines and its related molecule PPAR-γ. The experiments were performed using the RT-PCR technique in cultured 3T3-L1 adipocytes, in which the mRNA expression of leptin, adiponectin, resistin and PPAR-γ was recorded in the absence and presence of chitosan, O-CMCs and N-CQCs. The experimental results proved that chitosan, O-CMCs and N-CQCs not only lowered the level of plasma leptin, glucose, insulin and total cholesterol in vivo, but down-regulated mRNA expression of leptin and resistin, and up-regulated mRNA expression of adiponectin and PPAR-γ in vitro, to achieve the desired insulin resistance therapy.

Glucose oxidase induces insulin resistance via influencing multiple targets in vitro and in vivo: The central role of oxidative stress

It is well known that reactive oxygen species (ROS) plays a role in the pathogenesis of insulin resistance which is the hallmark of type 2 diabetes. However, it is still needed to clarify the mechanism underlying insulin resistance. Glucose oxidase (GOD) is an oxi-reductase catalyzing the conversion of glucose to glucolactone, which is further converted to glucuronic acid and H(2)O(2). The present study was designed to establish a rat model of insulin resistance using GOD and to investigate possible mechanisms. The results showed that three days administration of GOD could significantly increase fasting blood glucose, resulting in impaired glucose and insulin tolerance. Moreover, GOD disrupted insulin signaling both in rats and in hepatocytes, as evidenced by decreased phosphorylation of insulin-stimulated Akt, GSK3 and FOXO1α. Furthermore, GOD administration decreased the expression of PPARγ, alterated the phosphorylation of MAPKs, including p38, ERK and JNK, increased the expression of GRP78 and reduced the expression of PGC-1α and decreased the activities of ATPase and respiratory complexes, all of which have been reported to contribute to insulin resistance. Redox balance was evaluated by detecting the expression of antioxidant defenses and ROS generation. After the treatment with GOD, nuclear factorerythroid 2 p45-related factor 2 (Nrf2)-regulated antioxidant enzymes were damaged and ROS production increased significantly. N-acetyl-L-cysteine (NAC), a potent antioxidant, could notably inhibit these effects of GOD. Although further studies are needed to investigate the clear mechanism, these data also support the conclusion that, if not the most early event, ROS generation is the most important event that plays a central role in the pathogenesis of insulin resistance. Overall, our study established an insulin resistant animal model induced by GOD, elucidated the importance of ROS in pathogenesis of insulin resistance and provided the clue for further studies on the underlying mechanisms.

Effect of dietary fat on carbohydrate response element binding protein in a rat model of fatty liver and insulin resistance

The effect of obesity and insulin resistance on content and translocation of carbohydrate response element binding protein (ChREBP) was studied in dietary obese rats.MethodMale Sprague‐Dawley rats were separated into: LF (N=12) fed 55% carbohydrate: 15% fat (% kcal) and HF (N=8) fed 19% carbohydrate: 55% fat ad libitum for 8 weeks. Liver samples were collected from LF and HF after 20 h food deprivation (D) and then 3 h after oral glucose load (G). Liver protein extracts and homogenates, separated into cytoplasmic and nuclear fractions were analyzed by immunoblotting.ResultsIn the deprived state, total ChREBP was greater in HF than LF rats (P&lt;0.05). However, after the glucose load the level of total ChREBP was increased in LF, but not HF rats, resulting in similar levels of total ChREBP in the two groups. In addition, both groups showed similar increases in nuclear ChREBP content after the glucose load.ConclusionHigher basal levels of ChREBP protein in the obese group suggest higher basal hepatic fat synthesis than in the lean group. Given that post‐glucose ChREBP protein content and nuclear translocation were similar in both groups, the increase in ChREBP‐stimulated fat synthesis by glucose may be greater in the LF vs. HF group.Grant number:1 SC3 GM086298‐01A1Grant Funding Source : SC3GM086298

The effect of metformin on expression of vaspin mRNA in insulin resistant rats induced by high-fat diet

High-fat diet-induced insulin resistance rat model was assessed by euglycemic-hyperinsulinemic clamp technique.Compared with the control group,the vaspin mRNA expression in adipose tissue was significantly decreased in insulin resistant rats induced by high-fat diet( P＜0.05 ),which was increased by metformin( P＜0.05 ).These data indicate that metformin may ameliorate insulin resistance in rats via upregulating vaspin mRNA expression. Key words: Insulin resistance; Vaspin; Metformin; Euglycemic-hyperinsulinemic clamp; Rats

Effects of pioglitazone and/or simvastatin on circulating TNFα and adiponectin levels in insulin resistance

The current study investigated the effects of 14-day pioglitazone (PIO) and/or simvastatin (SIM) treatments on serum adiponectin (Adp) and TNFα levels (markers of adipocyte dysfunction), as well as on metabolic perturbations that arise from prolonged (8 week) consumption of a high fructose (HFD; 60%) diet in a rat model of pre-diabetic insulin resistance. The HFD induced a deranged lipid profile that was associated with adipose tissue hypertrophy, increased ratios of visceral and epididymal fats to body weight, and fatty liver. These perturbations were associated with hypo-adiponectinemia (50.8%) and increased serum TNFα (6.5-fold) levels. Treatment with PIO ameliorated the altered blood and hepatic glucose metabolism via an Adp-dependent mechanism; PIO also mitigated the changes in blood TNFα and led to a hyperelevation of Adp levels. SIM amended hepatic and overall lipid metabolism, regulated TNFα, but failed to alter the glucose intolerance or significantly impact on the HFD-altered Adp levels. Coadministration of SIM + PIO was superior in improving overall metabolic parameters compared to each monotherapy. Cotreatment was optimal in reestablishing insulin resistance, most efficacious in improving serum lipid profiles, normalizing percentage ratios of epididymal and visceral fats to body weight, and augmenting Adp/reducing TNFα levels relative to that in the HFD group or with HFD + each drug alone. The results here show that use of either monotherapy or a combined SIM + PIO approach might, from a clinical perspective, provide an ability to delay progression to Type 2 diabetes and its associated inflammatory/cardiovascular effects.

Effect of Sutherlandia frutescens on the Lipid Metabolism in an Insulin Resistant Rat Model and 3T3‐L1 Adipocytes

High fat diet induced insulin resistance correlates with dyslipidaemia and ectopic fat deposits in skeletal muscle and liver. The effects of Sutherlandia frutescens, an antidiabetic medicinal plant, on lipid metabolism were evaluated in an insulin resistant (IR) rat model and in 3 T3-preadipocytes. Wistar rats received normal diet (ND) or high fat diet (HFD). After the onset of IR in the HFD group, the rats were subdivided into two subgroups, which either continued with HFD or were treated with 50 mg S. frutescens/kg BW/day and HFD (HFD + SF). After 4 weeks, the HFD + SF rats had a significantly lower body weight than the HFD rats (p < 0.05). Blood plasma analysis showed a decrease in insulin, free fatty acids and triglycerides. Related changes in lipid parameters were observed in the liver, skeletal muscle and adipose tissue. To investigate the effects of S. frutescens on adipose tissue, 3 T3-L1 cells were used as a model. Treatment with S. frutescens led to a decrease in triglyceride accumulation, whilst glucose consumption and lactate production were increased (p < 0.05). These results indicate that S. frutescens directly affects mitochondrial activity and lipid biosynthesis in adipose tissue and provide a mechanism by which S. frutescens can restore insulin sensitivity by modulating fatty acid biosynthesis.

ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat model of cardiac dysfunction and insulin resistance

ObjectiveLow plasma high-density lipoprotein cholesterol (HDL-C) concentration is associated with the metabolic syndrome (MetS) and increased prevalence of cardiovascular disease (CVD). Animal and human studies report infusion of apolipoprotein A-1 (apoA-1) can reduce endothelial dysfunction, and/or induce regression of atherosclerosis. However, the direct mechanisms underlying the vascular benefits of either apoA-1 or HDL-C remain unclear. In this study, we assessed the ability of reconstituted HDL (rHDL) to improve vascular complications of MetS, including left ventricular (LV)-hypertrophy, arterial cholesterol deposition and myocardial lesion development. Methods and resultsObese insulin resistant (IR) JCR:LA-cp rats were infused with rHDL (0.4mg/kg) over 3 days before assessing cardiac function (Echocardiography) at days 7 and 50 post-infusion, as well as haematoxylin and eosin staining of myocardial lesions at day 50. Acute ex vivo arterial cholesterol deposition was assessed with acute infusion of rHDL ex-vivo. Infusion of rHDL partially corrected abnormal diastolic compliance (18%; *p<0.05) and improved parameters of cardiac function in IR rats. Further, acute rHDL infusion in carotid vessels reduced remnant lipoprotein associated-cholesterol deposition (30–86%; **p<0.01) ex vivo in IR and male Wistar rats and reduced (41%; *p<0.05) the frequency of early-stage myocardial lesions in IR rats. ConclusionShort-term infusion of rHDL may beneficially reduce chronic vascular sequelae of MetS, including temporary improvement in LV-dysfunction, acute reduction of acute arterial cholesterol deposition and the development of early-stage myocardial lesions in the JCR:LA-cp rat.

Thiazolidinedione Treatment Decreases Oxidative Stress in Spontaneously Hypertensive Heart Failure Rats Through Attenuation of Inducible Nitric Oxide Synthase–Mediated Lipid Radical Formation

The current study was designed to test the hypothesis that inducible nitric oxide synthase (iNOS)-mediated lipid free radical overproduction exists in an insulin-resistant rat model and that reducing the accumulation of toxic metabolites is associated with improved insulin signaling and metabolic response. Lipid radical formation was detected by electron paramagnetic resonance spectroscopy with in vivo spin trapping in an obese rat model, with or without thiazolidinedione treatment. Lipid radical formation was accompanied by accumulation of toxic end products in the liver, such as 4-hydroxynonenal and nitrotyrosine, and was inhibited by the administration of the selective iNOS inhibitor 1400 W. The model showed impaired phosphorylation of the insulin signaling pathway. Ten-day rosiglitazone injection not only improved the response to an oral glucose tolerance test and corrected insulin signaling but also decreased iNOS levels. Similar to the results with specific iNOS inhibition, thiazolidinedione dramatically decreased lipid radical formation. We demonstrate a novel mechanism where a thiazolidinedione treatment can reduce oxidative stress in this model through reducing iNOS-derived lipid radical formation. Our results suggest that hepatic iNOS expression may underlie the accumulation of lipid end products and that reducing the accumulation of toxic lipid metabolites contributes to a better redox status in insulin-sensitive tissues.

Nutritional regulation of adipose tissue lipoprotein lipase is blunted in insulin resistant rats

Abstract

Rosmarinic acid treatment alleviates fibrotic changes in the myocardium induced in a rat model of insulin resistance

ObjectiveThe objective of the present study is to investigate whether rosmarinic acid (RA) could prevent cardiac fibrosis induced in a rat model of insulin resistance. MethodsInsulin resistance was induced in rats by feeding a semi-synthetic diet containing fructose (60%) as the source of carbohydrate for 60 days. Control group received a diet containing starch in place of fructose. RA (10mg/kg) administration was initiated from the 16th day of the experimental period. Electrocardiography, fibrotic changes and reactive oxygen species (ROS) production were measured at the end of 60 days. ResultsFructose-fed rats (FFR) showed insulin resistance and significant changes in the electrocardiogram pattern and heart rate. Increased cardiac superoxide production (50%) accompanied by collagen deposition and increased expression of transforming growth factor (TGF)-β1, α-smooth muscle actin (α-SMA) and matrix metalloproteinase (MMPs)−2 and −9 and decreased expression of tissue inhibitors of MMP (TIMPs)−1 and −2 were noted in the FFR. This was accompanied by increased angiotensin II (AII) in plasma and angiotensin II type 1 receptor (AT1R) and fibronectin mRNA in heart. RA treatment restored the electrocardiographic patterns and regulated heart rate. The levels of superoxide, AII and collagen and the expression of TGF-β1, α-SMA, MMPs and AT1R were significantly reduced while the expression of TIMPs was increased upon RA treatment. Masson's trichrome stained heart sections revealed reduction in collagen in RA-supplemented FFR. ConclusionsWe conclude that RA treatment improves cardiac function and prevents myocardial fibrotic changes and hence could be useful as a cardioprotective agent under insulin resistant conditions.

Spirulina Reverses Histomorphological Changes in Diabetic Osteoporosis in Pioglitazone Treated Rats

Aim: The study was undertaken to assess the protective effect of Spirulina fusiform on risk fracture of bone in insulin resistance rat model and pharmacodynamics effects of Pioglitazone with Spirulina in treating hyperglycemia and hyperlipidaemia of insulin resistance rat. Method: For this aim, 30 Wistar albino rats were equally divided into five groups as control (NC), diabetes mellitus (DM), diabetes mellitus + Pioglitazone (DM+P), diabetes mellitus + Spirulina (DM+S), and diabetes mellitus + Pioglitazone + Spirulina (DM+P+S). Serum glucose, Triglyceride, HDL, LDL and insulin concentrations were estimated by standard methods in blood samples collected on 21st day. Morphological changes in pancreas and microarchitectual structure in femur bone were observed by histopathology studies. Results: A significant decrease in bone thickness was observed in Diabetes Mellitus rats group (p < 0.001) when compared to DM+P+S. In Pioglitazone with Spirulina treated group, the results demonstrated that the trabeculae bone thickness restored to original position and showed better restoration of beta cell in comparison to Spirulina treated and Pioglitazone treated group. The intactness and integrity of the bone surface as well as the bone strength also improved. Besides, chromium and gamma-linoleic acid in Spirulina helped to decrease the fasting serum glucose, HDL, LDL and triglycerides levels in insulin resistance rats. Conclusion: These findings suggest that combination therapy of Pioglitazone with Spirulina reduced the risk of fracture in insulin resistance rats. Additionally, Spirulina complemented the anti hyperglycemic and anti lipidemic activity of Pioglitazone.

Relationship of glucose and oleate metabolism to cardiac function in lipin-1 deficient (fld) mice

Lipin-1 is the major phosphatidate phosphatase (PAP) in the heart and a transcriptional coactivator that regulates fatty acid (FA) oxidation in the liver. As the control of FA metabolism is essential for maintaining cardiac function, we investigated whether lipin-1 deficiency affects cardiac metabolism and performance. Cardiac PAP activity in lipin-1 deficient [fatty liver dystrophy (fld)] mice was decreased by >80% compared with controls. Surprisingly, oleate oxidation and incorporation in triacylglycerol (TG), as well as glucose oxidation, were not significantly different in perfused working fld hearts. Despite this, [³H]oleate accumulation in phosphatidate and phosphatidylinositol was increased in fld hearts, reflecting the decreased PAP activity. Phosphatidate accumulation was linked to increased cardiac mammalian target of rapamycin complex 1 (mTORC1) signaling and endoplasmic reticulum (ER) stress. Transthoracic echocardiography showed decreased cardiac function in fld mice; however, cardiac dysfunction was not observed in ex vivo perfused working fld hearts. This showed that changes in systemic factors due to the global absence of lipin-1 could contribute to the decreased cardiac function in vivo. Collectively, this study shows that fld hearts exhibit unchanged oleate esterification, as well as oleate and glucose oxidation, despite the absence of lipin-1. However, lipin-1 deficiency increases the accumulation of newly synthesized phosphatidate and induces aberrant cell signaling.