Insulin Resistance In Wistar Rats Research Articles

Curcumin Treatment Ameliorates Hepatic Insulin Resistance Induced by Sub-chronic Oral Exposure to Cadmium LOAEL Dose via NF-κB and Nrf2 Pathways.

Cadmium (Cd) is a global pollutant, and its accumulation in the liver causes oxidative stress, inflammation, insulin resistance (IR), and metabolic complications. This study investigated whether curcumin treatment could alleviate hepatic IR in Wistar rats exposed to sub-chronic cadmium and explored the underlying molecular pathways. Male Wistar rats were divided into a control group (standard normocaloric diet + cadmium-free water) and a cadmium group (standard normocaloric diet + drinking water with 32.5ppm CdCl2) for 30days. Oral glucose tolerance, insulin response, and IR were assessed using mathematical models. Liver tissue was analyzed for markers of oxidative stress, inflammation, and key regulatory pathways, including NF-κB, Nrf2, MAPKs (JNK and p38), and the IRS1-Akt pathway. We established an effective curcumin dose of 250mg/kg for 5days orally. Results demonstrated that after 30days of exposure, cadmium accumulated in the liver, inducing an oxidative and inflammatory state. This was characterized by increased expression of NF-κB, JNK, and p38, along with diminished Nrf2 expression, hepatic IR, hyperglycemia, and hyperinsulinemia. Curcumin treatment effectively alleviated these metabolic disorders by restoring the balance between NF-κB and Nrf2 in the liver, modulating the MAPK pathway, and, consequently, improving oxidative and inflammatory balance. In conclusion, this study suggests that cadmium induces hepatic IR through an imbalance between NF-κB and Nrf2 signaling pathways. Curcumin treatment appears to improve these pathways, thereby ameliorating hepatic IR.

Insulin-sensitizing and antioxidant effects of <i>Ethulia</i> <i>conyzoïdes</i> aqueous extract in dexamethasone-induced insulin resistant rats

Rising the prevalence of type 2 diabetes mellitus in sub-saharian Africa has necessitated surveys of antidiabetic medicinal plants. Ethulia conyzoïdes is a plant widely used in traditional medicine to treat diabetes. However, the different mechanisms by which it exerts its antidiabetic effects remain unknown. Thus, this study aimed to investigate the effect of Ethulia conyzoïdes aqueoux extract on dexamethasone-induced insulin resistance in Wistar rats. Insulin resistance was induced by intraperitoneal injection of dexamethasone (1mg/kg) for 8 days and the animals received simultaneously, orally, distilled water (insulin resistant control group) and, metformin (100 mg/kg) or Ethulia conyzoïdes aqueoux extract at doses of 133 and 266 mg/kg. Normal control rats received NaCl 0.9% (intraperitoneal by injection) and distilled water orally. Insulin sensitivity, total cholesterol, triglycerides, transaminases activity and redox status were evaluated. Results showed a significant reduction of insulin tolerance (p<0.001), a drastic increased of transaminase activity (p<0.05), hyperlipidemia, and a great potentiation of liver antioxidant enzymes (GSH, SOD and catalase) in insulin resistant control group. Ethulia conyzoïdes aqueoux extract markedly improved insulin sensitivity and reversed all the modified parameters. This study demonstrated the efficacy of Ethulia conyzoïdes aqueoux extract to improve insulin sensitivity and manage biochemical disorders induced by insulin resistance. Short term administration of dexamethasone appears to stimulate the first line antioxidant defense in order to counteract oxidative stress, meaning that Ethulia conyzoïdes aqueoux extract inhibited free radicals production.

Hypercaloric Cafeteria Diet-Induces Obesity, Dyslipidemia, Insulin Resistance, Inflammation and Oxidative Stress in Wistar Rats

Obesity is a public health problem associated with oxidative stress, chronic inflammation, and insulin resistance. The present study analyzed the cafeteria diet's effects on obesity, oxidative stress, chronic inflammation, and insulin resistance in Wistar rats. Thirty-five male rats were divided into four groups: 1, control (n=10); 2, cafeteria diet (n=9) during 26 weeks (age relative to human adolescence); 3, control 38 weeks (n=9); 4, cafeteria diet during 38 weeks (n=7) (age relative to human adults). The percentage of total adipose tissue (TAT), body mass index, Lee's index, and insulin sensitivity (QUICKI-HOMA) were calculated, as well as metabolic parameters such as lipid profile, glucose levels, glycosylated hemoglobin, antioxidant and oxidative status, TNF-α, and IL-6. Both rat groups with cafeteria diet increased their weight 45.13±15.73 g and TAT 7.75 ± 0.64 g significantly at 26-week, and 46.7±9.05 g weight and TAT 9.97 ± 0.46 at 38 weeks compared to the control group (p<0.05 and p<0.01, respectively). Total cholesterol, HDL, LDL, triglycerides, glucose, Insulin, TBARS, GSH, and catalase activity levels increased in both 26 and 38-week groups vs. control (p<0.01), and TNF-α only at 26 weeks (p<0.01). In conclusion, the cafeteria diet induces obesity in rats, accompanied by hyperglycemia, dyslipidemia, oxidative stress, inflammation, insulin resistance, and TAT. Induction of obesity with a cafeteria diet could be used to study the mechanisms involved in the genesis of overweight, obesity, and comorbidities to establish intervention strategies to prevent these pathologies during adolescence and adulthood. Keywords: Inflammation, Oxidative Stress, Total Adipose Tissue, QUICKI-HOMA.

Effect of Ficus lacor Buch. Ham. Fruit Extract on Dexamethasone Induced Insulin Resistant Rats

Fruits of plant Ficus lacor Buch. Ham. were evaluated for its antidiabetic efficacy in dexamethasone induced insulin resistant rats. Extraction of fruits was done by soxhlation method to get fruit extract. Acute toxicity study of fruit extract was performed as per OECD 425 guidelines using wistar rats. Rats weighing between 200 to 250 g were selected for experimental work and divided randomly in to five groups normal control, diabetic Control, standard control (metformin, 2mg/kg), fruit extract (200mg/kg), fruit extract (400mg/kg) with five animals in each group. Dexamethasone (10mg/kg s.c) was used to induce insulin resistance in wistar rats weighing between 200 to 250g for 11 days. Animals in treatment group were treated with metformin (40mg/kg), fruit extract (200 and 400mg/kg) for 11 days daily. At the end of 11 days study, different parameters like body weight, food intake, water intake, glucose, cholesterol, triglyceride, HDL, LDL, VLDL, urea, uric acid, creatinine, aspartate aminotransferase (AST) and alanine transaminase (ALT) were determined. Liver and muscle was isolated for estimation of glycogen level. The result indicates significant (P ˂ 0.05) improvement in different biochemical parameters when compared with diabetic control group. The liver glycogen level was increased significantly (P ˂ 0.001) when compared with diabetic control group. The antidiabetic effect of fruit extract of plant Ficus Lacor Buch. Ham. was found to be dose dependent.

ROS and ERK Pathway Mechanistic Approach on Hepatic Insulin Resistance After Chronic Oral Exposure to Cadmium NOAEL Dose.

Cadmium is a critical toxic agent in occupational and non-occupational settings and acute and chronic environmental exposure situations that have recently been associated with metabolic disease development. Until now, the no observed adverse effect level (NOAEL) of cadmium has not been studied regarding insulin resistance development. Therefore, we aimed to monitor whether chronic oral exposure to cadmium NOAEL dose induces insulin resistance in Wistar rats and investigate if oxidative stress and/or inflammation are related. Male Wistar rats were separated into control (standard normocalorie diet + water free of cadmium) and cadmium groups (standard normocalorie diet + drinking water with 15ppm CdCl2). At 15, 30, and 60days, oral glucose tolerance, insulin response, and insulin resistance were analyzed using mathematical models. In the liver glycogen, triglyceride, pro- and anti-inflammatory cytokines, cadmium, zinc, metallothioneins, and redox balance were quantified. Immunoreactivity analysis of proteins involved in metabolic and mitogenic insulin signaling was performed. The results showed that a cadmium NOAEL dose after 15days of exposure causes ROS and mitogenic arm of insulin signaling to increase while hepatic glycogen diminishes. At 30days, Cd accumulation accentuated ROS production, hepatic triglyceride overaccumulation, and mitogenic signals that develop insulin resistance. Finally, inflammation and lipid peroxidation appear after 60days of Cd exposure, while lipids and carbohydrate homeostasis deteriorate. In conclusion, environmental exposure to cadmium NAOEL dose causes hepatic Cd accumulation and ROS overproduction that chronically declines the antioxidant defense, deteriorates metabolic homeostasis associated with the mitogenic pathway of insulin signaling, and induces insulin resistance.

Fructose prevents the development of hyperglycaemia in WBN/Kob diabetic fatty rats via maintaining high insulin levels.

Fructose is considered to negatively affect type 2 diabetes mellitus (T2DM); however, there are contradictory reports. The present study aimed to elucidate the effects of fructose-rich diet (FRD) on glucose metabolism of Wistar Bonn Kobori (WBN/Kob) fatty diabetic (WBKDF) rats, a spontaneous T2DM model, and Wistar rats. Wistar Bonn Kobori fatty diabetic and Wistar rats were fed either FRD or standard diet (STD) for 4weeks. The food intake, body weight, plasma glucose and insulin were measured weekly. After the 4-week challenge, rats were subjected to an intravenous glucose tolerance test (IVGTT). The liver and pancreas were used for histological analysis. The 4-week challenge of FRD in Wistar rats did not cause hyperglycaemia, but increased insulin resistance (Homeostatic Model Assessment for Insulin Resistance [HOMA-IR]). Feeding WBKDF rats with a FRD accelerated obesity, but prevented the onset of severe hyperglycaemia via maintaining high plasma insulin levels. Homeostatic Model Assessment for Insulin Resistance in WBKDF rats was not changed by FRD feeding. Intravenous glucose tolerance test revealed that FRD feeding in Wistar rats did not affect glucose tolerance, but slightly increased the plasma insulin level. In contrast, FRD feeding in WBKDF rats significantly reduced the glucose tolerance, but insulin response was not improved. Fructose-rich diet feeding did not alter the β cell area in Wistar rats, but significantly increased it in WBKDF rats. In conclusion, FRD caused insulin resistance in Wistar rats, suggesting that fructose overconsumption is a risk factor for T2DM, whereas FRD inhibited severe hyperglycaemia by maintaining high insulin levels in WBKDF rats. Fructose may be a beneficial sugar for T2DM patients with severe obesity-induced insulin resistance.

The Roles of Liver Inflammation and the Insulin Signaling Pathway in PM2.5 Instillation-Induced Insulin Resistance in Wistar Rats.

To elucidate the mechanism of how the liver participates in PM2.5-caused insulin resistance. A novel Wistar rat model was developed in this study by instilling a suspension of lyophilized PM2.5 sample (2.5 mg/kg, 5 mg/kg, or 10 mg/kg) collected from the atmosphere. Systemic insulin resistance indicators, including serum fasting blood glucose (FBG), fasting insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and hemoglobin A1 (HbA1), were upregulated by the PM2.5 instillation. The area under the curve (AUCglu) calculated by intraperitoneal glucose tolerance testing (IPGTT) was also significantly greater in the PM2.5 instillation groups. Additionally, PM2.5 instillation was found to cause liver damage and inflammation. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly elevated by PM2.5 instillation. PM2.5 also triggered IL-6 and TNF-α transcription but inhibited mRNA synthesis and suppressed signaling activation of the insulin-phosphoinositide 3-kinase- (PI3K-) Akt-glucose transporter 2 (GLUT2) pathway in the rat liver by reducing the ratio of phosphorylated Akt to phosphorylated insulin receptor substrate 1 (IRS-1). Thus, PM2.5-induced inflammation activation and insulin signaling inhibition in the rat liver contribute to the development of systemic insulin resistance.

D-Allulose Ameliorates Skeletal Muscle Insulin Resistance in High-Fat Diet-Fed Rats.

Background: d-Allulose is a rare sugar with antiobesity and antidiabetic activities. However, its direct effect on insulin sensitivity and the underlying mechanism involved are unknown. Objective: This study aimed to investigate the effect of d-allulose on high-fat diet (HFD)-induced insulin resistance using the hyperinsulinemic–euglycemic (HE)-clamp method and intramuscular signaling analysis. Methods: Wistar rats were randomly divided into three dietary groups: chow diet, HFD with 5% cellulose (HFC), and HFD with 5% d-allulose (HFA). After four weeks of feeding, the insulin tolerance test (ITT), intraperitoneal glucose tolerance test (IPGTT), and HE-clamp study were performed. The levels of plasma leptin, adiponectin, and tumor necrosis factor (TNF)-α were measured using the enzyme-linked immunosorbent assay. We analyzed the levels of cell signaling pathway components in the skeletal muscle using Western blotting. Results: d-allulose alleviated the increase in HFD-induced body weight and visceral fat and reduced the area under the curve as per ITT and IPGTT. d-Allulose increased the glucose infusion rate in the two-step HE-clamp test. Consistently, the insulin-induced phosphorylation of serine 307 in the insulin receptor substrate-1 and Akt and expression of glucose transporter 4 (Glut-4) in the muscle were higher in the HFA group than HFC group. Furthermore, d-allulose decreased plasma TNF-α concentration and insulin-induced phosphorylation of stress-activated protein kinase/Jun N-terminal kinase in the muscle and inhibited adiponectin secretion in HFD-fed rats. Conclusions: d-allulose improved HFD-induced insulin resistance in Wistar rats. The reduction of the proinflammatory cytokine production, amelioration of adiponectin secretion, and increase in insulin signaling and Glut-4 expression in the muscle contributed to this effect.

The Role of High Fat Diets and Liver Peptidase Activity in the Development of Obesity and Insulin Resistance in Wistar Rats.

High-fat diets (HFD) have been widely associated with an increased risk of metabolic disorders and overweight. However, a high intake of sources that are rich in monounsaturated fatty acids has been suggested as a dietary agent that is able to positively influence energy metabolism and vascular function. The main objective of this study was to analyze the role of dietary fats on hepatic peptidases activities and metabolic disorders. Three diets: standard (S), HFD supplemented with virgin olive oil (VOO), and HFD supplemented with butter plus cholesterol (Bch), were administered over six months to male Wistar rats. Plasma and liver samples were collected for clinical biochemistry and aminopeptidase activities (AP) analysis. The expression of inducible nitric oxide synthase (iNOS) was also determined by Western blot in liver samples. The diet supplement with VOO did not induce obesity, in contrast to the Bch group. Though the VOO diet increased the time that was needed to return to the basal levels of plasma glucose, the fasting insulin/glucose ratio and HOMA2-%B index (a homeostasis model index of insulin secretion and valuation of β-cell usefulness (% β-cell secretion)) were improved. An increase of hepatic membrane-bound dipeptidyl-peptidase 4 (DPP4) activity was found only in VOO rats, even if no differences in fasting plasma glucagon-like peptide 1 (GLP-1) were obtained. Both HFDs induced changes in hepatic pyroglutamyl-AP in the soluble fraction, but only the Bch diet increased the soluble tyrosyl-AP. Angiotensinase activities that are implicated in the metabolism of angiotensin II (AngII) to AngIV increased in the VOO diet, which was in agreement with the higher activity of insulin-regulated-AP (IRAP) in this group. Otherwise, the diet that was enriched with butter increased soluble gamma-glutamyl transferase (GGT) and Leucyl-AP, iNOS expression in the liver, and plasma NO. In summary, VOO increased the hepatic activity of AP that were related to glucose metabolism (DPP4, angiotensinases, and IRAP). However, the Bch diet increased activities that are implicated in the control of food intake (Tyrosine-AP), the index of hepatic damage (Leucine-AP and GGT), and the expression of hepatic iNOS and plasma NO. Taken together, these results support that the source of fat in the diet affects several peptidases activities in the liver, which could be related to alterations in feeding behavior and glucose metabolism.

Effect of intranasal insulin on peripheral glucose profile in dexamethasone-induced insulin resistance in Wistar rats

This study evaluates the therapeutic potential of intranasal insulin (INI) in dexamethasone-induced insulin resistance in Wistar rats. In the first phase of the study, thirteen, healthy, untreated male Wistar rats were divided into 2 groups and administered either vehicle (0.9% Normal saline, 20 µl) or insulin (2 IU) intranasally to assess intranasal delivery of insulin in brain. In the second phase of experiments, to evaluate the acute effects of intranasal insulin on peripheral blood glucose, intranasal or intraperitoneal insulin was co-administered with or without dexamethasone 10 mg/kg to 26 male Wistar rats and blood glucose monitored. To evaluate effect of intranasal insulin in peripheral metabolic disease model, insulin or vehicle was administered via intranasal or intraperitoneal (IP) route to control or dexamethasone (Dex)-treated (0.5 mg/kg, IP) female Wistar rats for seven consecutive days. Twenty-four hours after last dose, trunk blood was collected via cardiac puncture. Biochemical assay of glucose, lipid and insulin was performed on serum while enzyme activity – glucokinase and glucose-6-phosphatase (G6Pase) or lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PDH) were assayed from liver and brain homogenates respectively. Acute intranasal but not intraperitoneal insulin elevated brain insulin after 30 min. In animals administered single dose of 10 mg/kg dexamethasone, intranasal and intraperitoneal insulin lowered blood glucose within one hour. However, only the former’s effect was maintained at the 3rd and fourth hour. Dex-induced hyperglycemia was associated with increased hepatic glucose-6-phosphatase activity and decreased high-density lipoprotein (HDL), these effect were attenuated by subchronic (INI) administration. Also INI did not induce oxidative stress in the brain which suggests no brain damage during the period of study. Subchronic administration of INI was able to reduce the effect of Dex-induced hyperglycemia that is associated with increased hepatic glucose-6-phosphatase activity and decreased high-density lipoprotein (HDL) without damage to the brain. We demonstrate the potential of brain targeting with intranasal insulin in a rat model of insulin resistance and peripheral metabolic disease.

Bifidobacterium spp. reshaping in the gut microbiota by low dose of juçara supplementation and hypothalamic insulin resistance in Wistar rats

High-fat diet (HFD) alters gut microbial diversity and drives a rapid development of hypothalamic inflammation, which impairs hypothalamic insulin sensitivity. The addition of berries in the diet may promote beneficial effects in the host. We investigated the potential of juçara with different doses on the reshaping of the microbiota and improvement in the hypothalamic insulin resistance (HIR) induced by acute HFD treatment. We analyzed pro and anti-inflammatory protein content and expression by ELISA (blood and colon) and Western blotting (hypothalamus); gene expression by RT-PCR (colon and stool). Juçara supplementation restored the fecal Bifidobacteria content, reduced colon inflammation and minimized HIR. It also down-regulated IRα and up-regulated pAkt and increased pAkt/Akt ratio. The lower dose was protective against the adverse effects of HFD, by enhancing IRα efficiency in the hypothalamus. To our knowledge, this is the first study to elucidate the role of juçara in the HIR.

Intermittent fasting for three months decreases pancreatic islet mass and increases insulin resistance in Wistar rats

Intermittent fasting for three months decreases pancreatic islet mass and increases insulin resistance in Wistar rats

Combined Heat Treatment and Exercise Prevents Skeletal Muscle Insulin Resistance in Wistar Rats Fed a High-Fat Diet

PURPOSE: Insulin resistance (IR) is associated with many related health complications. Previous studies demonstrate that heat and exercise independently reduce IR. The purpose of this study was to test the hypothesis that combined exercise and heating is even more favorable in reducing IR. METHODS: Male Wistar rats were randomly divided into five groups: exercise (NE; n=10), heated (HC; n=10), exercise and heated (HE; n=10), sedentary (NC; n=10), and normal diet plus sedentary (CC; n=10). All but the latter group was fed a high-fat diet (60% calories from fat) for 10 weeks while receiving heat and/or exercise exposure for latter 8 weeks. Following this regimen, protein expression from the soleus and extensor digitorum longus muscles, serum, and brown fat were analyzed using Western blotting. RESULTS: Exercise combined with heating shifted the metabolic characteristics of rats on a high-fat diet toward that observed in the rats on a standard diet. Specifically, eight weeks of combined heat and endurance exercise increased PGC-1α, CnA, CaMKIV and p38 MAPK protein expression in the soleus (P < 0.05), insulin protein expression in the serum (P < 0.05), and UCP1 protein expression in the brown fat (P < 0.05), when compared to the high fat fed sedentary group. There were some significant differences in responses (i.e., body weight and Leptin & Adiponectin concentrations) between the combined exercise and heat group relative to the exercise alone group. CONCLUSIONS: Exercise combined with heat exposure mitigates the development of IR, presumably from the Irisin pathway. The study provides potential non- pharmaceutical methods for therapeutic treatment of IR. KEY WORDS: Insulin resistance (IR); Exercise; Heat; Irisin This work was supported by The National Natural Science Foundation of China (31371195).

Comparison of Goto-Kakizaki rats and high fat diet-induced obese rats: Are they reliable models to study Type 2 Diabetes mellitus?

Type 2 Diabetes mellitus (T2DM) is an evident growing disease that affects different cultures throughout the world. T2DM occurs under the influence of three main factors: the genetic background, environmental and behavioral components. Obesity is strongly associated to the development of T2DM in the occident, while in the orient most of the diabetic patients are considered lean. Genetics may be a key factor in the development of T2DM in societies where obesity is not a recurrent public health problem. Herein, two different models of rats were used to understand their differences and reliability as experimental models to study the pathophysiology of T2DM, in two different approaches: the genetic (GK rats) and the environmental (HFD-induced obese rats) influences. GK rats were resistant to weight gain even though food/energy consumption (relative to body weight) was higher in this group. HFD, on the other hand, induced obesity in Wistar rats. White adipose tissue (WAT) expansion in this group was accompanied by immune cells infiltration, inflammation and insulin resistance. GK rats also presented WAT inflammation and insulin resistance; however, no immune cells infiltration was observed in the WAT of this group. Liver of HFD group presented fat accumulation without differences in inflammatory cytokines content, while liver of GK rats didn’t present fat accumulation, but showed an increase of IL-6 and IL-10 content and glycogen. Also, GK rats showed increased plasma GOT and GPT. Soleus muscle of HFD presented normal insulin signaling, contrary to GK rats, which presented higher content of basal phosphorylation of GSK-3β. Our results demonstrated that HFD developed a mild insulin resistance in Wistar rats, but was not sufficient to develop T2DM. In contrast, GK rats presented all the typical hallmarks of T2DM, such as insulin resistance, defective insulin production, fasting hyperglycemia/hyperinsulinemia and lipid plasma alteration. Thus, on the given time point of this study, we may conclude that only GK rats shown to be a reliable model to study T2DM.

Validation of HOMA-IR in a model of insulin-resistance induced by a high-fat diet in Wistar rats.

Objective The present study aimed to validate homeostasis model assessment of insulin resistance (HOMA-IR) in relation to the insulin tolerance test (ITT) in a model of insulin-resistance in Wistar rats induced by a 19-week high-fat diet. Materials and methods A total of 30 male Wistar rats weighing 200-300 g were allocated into a high-fat diet group (HFD) (55% fat-enriched chow, ad lib, n = 15) and a standard-diet group (CD) standard chow, ad lib, n = 15), for 19 weeks. ITT was determined at baseline and in the 19th week. HOMA-IR was determined between the 18-19th week in three different days and the mean was considered for analysis. Area under the curve (AUC-ITT) of the blood glucose excursion along 120 minutes after intra-peritoneal insulin injection was determined and correlated with the corresponding fasting values for HOMA-IR. Results AUC-ITT and HOMA-IR were significantly greater after 19th week in HFD compared to CD (p < 0.001 for both). AUC-OGTT was also higher in HFD rats (p = 0.003). HOMA-IR was strongly correlated (Pearson's) with AUC-ITT r = 0.637; p < 0.0001. ROC curves of HOMA-IR and AUC-ITT showed similar sensitivity and specificity. Conclusion HOMA-IR is a valid measure to determine insulin-resistance in Wistar rats. Arch Endocrinol Metab. 2016;60(2):138-42.

Effect of an avocado oil-enhanced diet (Persea americana) on sucrose-induced insulin resistance in Wistar rats

A number of studies have been conducted to evaluate the effects of vegetable oils with varying percentages of monounsaturated and polyunsaturated fatty acids on insulin resistance. However, there is no report on the effect of avocado oil on this pathologic condition. The aim of this work was to evaluate the effect of avocado oil on sucrose-induced insulin resistance in Wistar rats. An experimental study was carried out on Wistar rats that were randomly assigned into six groups. Each group received a different diet over an 8-week period (n = 11 in each group): the control group was given a standard diet, and the other five groups were given the standard feed plus sucrose with the addition of avocado oil at 0%, 5%, 10%, 20%, and 30%, respectively. Variables were compared using Student t test and analysis of variance. Statistically significant difference was considered when p < 0.05. Rats that were given diets with 10% and 20% avocado oil showed lower insulin resistance (p = 0.022 and p = 0.024, respectively). Similar insulin resistance responses were observed in the control and 30% avocado oil addition groups (p = 0.85). Addition of 5–30% avocado oil lowered high sucrose diet-induced body weight gain in Wistar rats. It was thus concluded that glucose tolerance and insulin resistance induced by high sucrose diet in Wistar rats can be reduced by the dietary addition of 5–20% avocado oil.

Quercetin Curtails Obesity and Dyslipidemia, but Not Insulin Resistance in Long-Term Type 2 Diabetic Male Wistar Rats Fed the High-Fat, High-Sucrose Diet

It is unclear whether the persistence of Type 2 Diabetes (T2D)-associated insulin resistance in Wistar rats is entirely dependent on obesity and dyslipidemia or other factors are involved. We wanted to reveal whether alleviation of obesity and dyslipidemia by quercetin would sufficiently cure the insulin resistance in diabetic Wistar rats. For this purpose, ninety, male Wistar rats were randomized into three experimental groups (n=30): Normal Control (NC) fed chow diet, Diabetic Control (DC) fed High-Fat, High- Sucrose Diet (HFHSD) and diabetic, Quercetin-Treated (QT) fed the HFHSD and gavaged with quercetin at 50 mg.kg-1 bw.day-1. On Days 0, 60 and 120, Body Mass Index (BMI) and Abdominal Circumference:Thoracic Circumference (AC:TC) ratio were measured on ten rats from each group. Rats were then euthanized and fasting blood samples were withdrawn and used to quantify plasma glucose, Triacyclglycerols (TAG), LDL-cholesterol, total cholesterol, C-Reactive Protein (CRP) and insulin concentrations. Insulin resistance score, Relative Pancreatic Weight (RPW, %) and number of islet of Langerhans were also determined. We show that quercetin normalized BMI, AC:TC ratio, RPW (%) and dyslipidemia, and enhanced the islets number of Langerhans in the QT rats on Day 120 relative to the NC rats. In the diabetic DC rats, AC:TC ratio correlated positively with hyperglycemia and negatively with RPW (%). Quercetin lowered, but failed to normalize hyperinsulinemia, insulin resistance score, hyperglycemia and CRP in the QT rats relative to the NC rats suggesting that other factors are involved in the insulin resistance pathogenesis in T2D Wistar rats. Our data also suggest that AC:TC ratio is a predictor of the obesity-induced T2D in Wistar rats.

Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats

In a previous study, we showed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. We now question whether it could be due to the sweet taste of saccharin per se. We also aimed to address if this weight gain is associated with insulin-resistance and to increases in gut peptides such as leptin and PYY in the fasting state. In a 14 week experiment, 16 male Wistar rats received either saccharin-sweetened yogurt or non-sweetened yogurt daily in addition to chow and water ad lib. We measured daily food intake and weight gain weekly. At the end of the experiment, we evaluated fasting leptin, glucose, insulin, PYY and determined insulin resistance through HOMA-IR. Cumulative weight gain and food intake were evaluated through linear mixed models. Results showed that saccharin induced greater weight gain when compared with non-sweetened control (p = 0.027) despite a similar total caloric intake. There were no differences in HOMA-IR, fasting leptin or PYY levels between groups. We conclude that saccharin sweet taste can induce mild weight gain in Wistar rats without increasing total caloric intake. This weight gain was not related with insulin-resistance nor changes in fasting leptin or PYY in Wistar rats.

Discovery of novel glitazones incorporated with phenylalanine and tyrosine: Synthesis, antidiabetic activity and structure–activity relationships

We report a series of new glitazones incorporated with phenylalanine and tyrosine. All the compounds were tested for their in vitro glucose uptake activity using rat-hemidiaphragm, both in presence and absence of insulin. Six of the most active compounds from the in vitro screening were taken forward for their in vivo triglyceride and glucose lowering activity against dexamethazone induced hyperlipidemia and insulin resistance in Wistar rats. The liver samples of rats that received the most active compounds, 23 and 24, in the in vivo studies, were subjected to histopathological examination to assess their short term hepatotoxicity. The investigations on the in vitro glucose uptake, in vivo triglyceride and glucose lowering activity are described here along with the quantitative structure–activity relationships.

Cafeteria diet intake for fourteen weeks can cause obesity and insulin resistance in Wistar rats

OBJECTIVE: Obesity is a strong predictor of some kinds of diseases. High intake of high-fat foods contributes significantly to the growth of the obese population globally. The aim of this study was to verify if consumption of a cafeteria diet for fourteen weeks could increase white fat mass, body weight and skeletal muscle mass and promote insulin resistance in male Wistar rats. METHODS: Twenty animals were divided into two groups: control and obese. Both were fed standard chow and water ad libitum. Additionally, a cafeteria diet consisting of bacon, bologna sausage, sandwich cookies and soft drink was given to the obese group. RESULTS: The obese group was significantly heavier (p&lt;0.0001) than controls from the second week until the end of the cafeteria-diet intervention. Absolute and relative fat mass, liver weight and Lee Index increased significantly (p&lt;0.05) in the obese group. Furthermore, the obese group had lower (p&lt;0.05) insulin sensitivity than the control group. CONCLUSION: In conclusion, fourteen weeks of cafeteria diet promoted a progressive increase of fat mass and insulin resistance. Therefore, this is a great and inexpensive diet-induced insulin resistance model.