Validation of simple indexes to assess insulin sensitivity during pregnancy in Wistar and Sprague-Dawley rats

2008 ◽  
Vol 295 (5) ◽  
pp. E1269-E1276 ◽  
Author(s):  
J. Cacho ◽  
J. Sevillano ◽  
J. de Castro ◽  
E. Herrera ◽  
M. P. Ramos
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Fasting Glucose ◽  
Roc Curves ◽  
Glucose Clamp ◽  
Model Assessment ◽  
Sprague Dawley ◽  
Insulin Levels ◽  
Sprague Dawley Rats

Insulin resistance plays a role in the pathogenesis of diabetes, including gestational diabetes. The glucose clamp is considered the gold standard for determining in vivo insulin sensitivity, both in human and in animal models. However, the clamp is laborious, time consuming and, in animals, requires anesthesia and collection of multiple blood samples. In human studies, a number of simple indexes, derived from fasting glucose and insulin levels, have been obtained and validated against the glucose clamp. However, these indexes have not been validated in rats and their accuracy in predicting altered insulin sensitivity remains to be established. In the present study, we have evaluated whether indirect estimates based on fasting glucose and insulin levels are valid predictors of insulin sensitivity in nonpregnant and 20-day-pregnant Wistar and Sprague-Dawley rats. We have analyzed the homeostasis model assessment of insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI), and the fasting glucose-to-insulin ratio (FGIR) by comparing them with the insulin sensitivity (SIClamp) values obtained during the hyperinsulinemic-isoglycemic clamp. We have performed a calibration analysis to evaluate the ability of these indexes to accurately predict insulin sensitivity as determined by the reference glucose clamp. Finally, to assess the reliability of these indexes for the identification of animals with impaired insulin sensitivity, performance of the indexes was analyzed by receiver operating characteristic (ROC) curves in Wistar and Sprague-Dawley rats. We found that HOMA-IR, QUICKI, and FGIR correlated significantly with SIClamp, exhibited good sensitivity and specificity, accurately predicted SIClamp, and yielded lower insulin sensitivity in pregnant than in nonpregnant rats. Together, our data demonstrate that these indexes provide an easy and accurate measure of insulin sensitivity during pregnancy in the rat.

scholarly journals Effects of Micronutrient Supplementation on Glucose and Hepatic Lipid Metabolism in a Rat Model of Diet Induced Obesity

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1751
Author(s):  
Saroj Khatiwada ◽  
Virginie Lecomte ◽  
Michael F. Fenech ◽  
Margaret J. Morris ◽  
Christopher A. Maloney
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Glucose Tolerance ◽  
Antioxidant Capacity ◽  
Fasting Glucose ◽  
Oral Glucose ◽  
Model Assessment ◽  
Micronutrient Supplementation ◽  
Sprague Dawley ◽  
Triglyceride Accumulation

Obesity increases the risk of metabolic disorders, partly through increased oxidative stress. Here, we examined the effects of a dietary micronutrient supplement (consisting of folate, vitamin B6, choline, betaine, and zinc) with antioxidant and methyl donor activities. Male Sprague Dawley rats (3 weeks old, 17/group) were weaned onto control (C) or high-fat diet (HFD) or same diets with added micronutrient supplement (CS; HS). At 14.5 weeks of age, body composition was measured by magnetic resonance imaging. At 21 weeks of age, respiratory quotient and energy expenditure was measured using Comprehensive Lab Animal Monitoring System. At 22 weeks of age, an oral glucose tolerance test (OGTT) was performed, and using fasting glucose and insulin values, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated as a surrogate measure of insulin resistance. At 30.5 weeks of age, blood and liver tissues were harvested. Liver antioxidant capacity, lipids and expression of genes involved in lipid metabolism (Cd36, Fabp1, Acaca, Fasn, Cpt1a, Srebf1) were measured. HFD increased adiposity (p < 0.001) and body weight (p < 0.001), both of which did not occur in the HS group. The animals fed HFD developed impaired fasting glucose, impaired glucose tolerance, and fasting hyperinsulinemia compared to control fed animals. Interestingly, HS animals demonstrated an improvement in fasting glucose and fasting insulin. Based on insulin release during OGTT and HOMA-IR, the supplement appeared to reduce the insulin resistance developed by HFD feeding. Supplementation increased hepatic glutathione content (p < 0.05) and reduced hepatic triglyceride accumulation (p < 0.001) regardless of diet; this was accompanied by altered gene expression (particularly of CPT-1). Our findings show that dietary micronutrient supplementation can reduce weight gain and adiposity, improve glucose metabolism, and improve hepatic antioxidant capacity and lipid metabolism in response to HFD intake.

scholarly journals Muscle insulin resistance resulting from impaired microvascular insulin sensitivity in Sprague Dawley rats

2013 ◽  
Vol 98 (1) ◽  
pp. 28-36 ◽  
Author(s):  
Dino Premilovac ◽  
Eloise A. Bradley ◽  
Huei L.H. Ng ◽  
Stephen M. Richards ◽  
Stephen Rattigan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Sprague Dawley ◽  
Muscle Insulin Resistance ◽  
Sprague Dawley Rats

scholarly journals Electroacupuncture Mitigates Skeletal Muscular Lipid Metabolism Disorder Related to High-Fat-Diet Induced Insulin Resistance through the AMPK/ACC Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Zhixing Li ◽  
Danchun Lan ◽  
Haihua Zhang ◽  
Hongtao Zhang ◽  
Xiaozhuan Chen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Control Group ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Sprague Dawley ◽  
High Fat ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder

The aim of this work is to investigate the effect of electroacupuncture (EA) on insulin sensitivity in high-fat diet (HFD) induced insulin resistance (IR) rats and to evaluate expression of AMPK/ACC signaling components. Thirty-two male Sprague-Dawley rats were randomized into control group, HFD group, HFD+Pi (oral gavage of pioglitazone) group, and HFD+EA group. Acupuncture was subcutaneously applied to Zusanli (ST40) and Sanyinjiao (SP6). For Zusanli (ST40) and Sanyinjiao (SP6), needles were connected to an electroacupuncture (EA) apparatus. Fasting plasma glucose was measured by glucose oxidase method. Plasma fasting insulin (FINS) and adiponectin (ADP) were determined by ELISA. Triglyceride (TG) and cholesterol (TC) were determined by Gpo-pap. Proteins of adiponectin receptor 1 (adipoR1), AMP-activated Protein Kinase (AMPK), and acetyl-CoA carboxylase (ACC) were determined by Western blot, respectively. Compared with the control group, HFD group exhibits increased levels of FPG, FINS, and homeostatic model assessment of insulin resistance (HOMA-IR) and decreased level of ADP and insulin sensitivity index (ISI). These changes were reversed by both EA and pioglitazone. Proteins of adipoR1 and AMPK were decreased, while ACC were increased in HFD group compared to control group. Proteins of these molecules were restored back to normal levels upon EA and pioglitazone. EA can improve the insulin sensitivity of insulin resistance rats; the positive regulation of the AMPK/ACC pathway in the skeletal muscle may be a possible mechanism of EA in the treatment of IR.

scholarly journals Dietary fructo-oligosaccharides improve insulin sensitivity along with the suppression of adipocytokine secretion from mesenteric fat cells in rats

2011 ◽  
Vol 106 (8) ◽  
pp. 1190-1197 ◽  
Author(s):  
Aki Shinoki ◽  
Hiroshi Hara
Keyword(s):  
Insulin Resistance ◽  
Small Intestine ◽  
Insulin Sensitivity ◽  
Control Diet ◽  
Control Group ◽  
Dependent Manner ◽  
Model Assessment ◽  
Sprague Dawley ◽  
Aortic Blood ◽  
Mesenteric Fat

Short-chain fructo-oligosaccharides (FOS) are known to have beneficial effects on health. However, the effects of FOS on insulin resistance have not been fully clarified. We observed the effects of FOS feeding on insulin sensitivity and adipocytokine release from abdominal adipocytes in weaning rats. Male Sprague–Dawley rats, 3 weeks old, were divided into three groups and fed a sucrose-based American Institute of Nutrition (AIN)-93 growth diet (control), the control diet containing 5 % FOS for 5 weeks (FOS-5wk) or the control diet for 2 weeks followed by the 5 % FOS diet for 3 weeks (FOS-3wk). Tail blood was collected after fasting for 9 h on day 33 of feeding, and glucose and insulin levels were measured. On the last day, rats were anaesthetised and killed after the collection of aortic blood. Small- and large-intestinal mesenteric fat tissues were immediately excised, and the release of adiponectin, leptin and TNF-α was evaluated from the subsequently isolated adipocytes. The weight of the large-intestinal mesenteric fat, fasting blood insulin level and homeostatic model assessment for insulin resistance decreased in a time-dependent manner, and were much lower in the FOS-5wk group than in the control group. These values were correlated with aortic blood leptin levels. The secretion rate of leptin from the isolated mesenteric adipocytes in the small intestine, but not in the large intestine, was lower in the FOS-fed groups than in the control group. In conclusion, FOS feeding improved insulin sensitivity accompanied by the reduction in large-intestinal fat mass and leptin secretion from the mesenteric adipocytes of the small intestine.

scholarly journals Metformin improves polycystic ovary syndrome symptoms irrespective of pre-treatment insulin resistance

2007 ◽  
Vol 157 (5) ◽  
pp. 669-676 ◽  
Author(s):  
Susanne Tan ◽  
Susanne Hahn ◽  
Sven Benson ◽  
Tiina Dietz ◽  
Harald Lahner ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Fasting Glucose ◽  
Polycystic Ovary ◽  
Model Assessment ◽  
Fasting Insulin ◽  
Ovary Syndrome ◽  
Insulin Levels ◽  
Outcome Parameters ◽  
Pre Treatment

AbstractObjectiveInsulin resistance (IR) and obesity are common features of the polycystic ovary syndrome (PCOS). Insulin-sensitizing agents have been shown to improve both reproductive and metabolic aspects of PCOS, but it remains unclear whether it is also beneficial in lean patients without pre-treatment IR. The aim of this study was to determine the influence of metformin on the clinical and biochemical parameters of PCOS irrespective of the presence of basal obesity and IR.DesignThe effect of 6 months of metformin treatment was prospectively assessed in 188 PCOS patients, divided into three groups according to body mass index (BMI; lean: BMI<25 kg/m2, overweight: BMI 25–29 kg/m2, and obese: BMI≥30 kg/m2). Outcome parameters, which were also assessed in 102 healthy controls, included body weight, homeostasis model assessment for IR (HOMA-IR), fasting glucose and insulin levels, area under the curve of insulin response (AUCI), hyperandrogenism, and menstrual irregularities.ResultsIn comparison with the respective BMI-appropriate control groups, only obese but not lean and overweight PCOS patients showed differences in fasting insulin and HOMA-IR. Metformin therapy significantly improved all outcome parameters except fasting glucose levels. Subgroup analyses revealed that in the group of lean PCOS patients without pre-treatment IR, metformin significantly improved HOMA-IR (1.7±1.0 vs 1.1±0.7 μmol/l×mmol/l2) and fasting insulin levels (7.7±4.2 vs 5.4±3.9 mU/l), in addition to testosterone levels (2.6±0.9 vs 1.8±0.7 nmol/l), anovulation rate (2.3 vs 59.5%), and acne (31.8 vs 11.6%; all P<0.017). In the overweight and obese PCOS groups, metformin also showed the expected beneficial effects.ConclusionMetformin improves parameters of IR, hyperandrogenemia, anovulation, and acne in PCOS irrespective of pre-treatment IR or obesity.

scholarly journals An animal model of gestational obesity and prediabetes: HISS-dependent insulin resistance induced by a high sucrose diet in Sprague Dawley rats.

2020 ◽  
Author(s):  
Nicole Eleanore Jacqueline Lovat ◽  
Dallas J. Legare ◽  
W. Wayne Lautt
Keyword(s):  
Insulin Resistance ◽  
Animal Model ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Complete Recovery ◽  
Partial Recovery ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Nutrient Partitioning ◽  
Insulin Dependent

This study developed an animal model of gestational obesity and prediabetes in Sprague Dawley rats using 35% sucrose supplementation (SS). Postprandially, insulin stimulates glucose uptake and nutrient partitioning via insulin-dependent as well as Hepatic Insulin Sensitizing Substance (HISS)-dependent action. HISS is glycogenic in heart, kidney, and skeletal muscle (contrasting insulin’s lipogenic actions in liver and adipose tissue) and is responsible for the vasodilatory action of insulin. Post-prandial insulin sensitivity was quantified using the Rapid Insulin Sensitivity Test (RIST). 15-day gestation and virgin animals received SS for 8-weeks (with a 2-week recovery), 10-weeks or 22-weeks. SS in pregnant and virgin rats eliminated HISS-dependent glucose uptake, resulting in compensatory hyperinsulinemia and resultant hypertriglyceridemia and obesity. In groups with SS for 8-weeks followed by a 2-week recovery, there was spontaneous partial recovery of HISS-dependent glucose uptake in virgins and complete recovery in pregnancy. 10-week SS resulted in complete absence of HISS-dependent glucose uptake and produced a model of gestational obesity and prediabetes. 22-week SS did not produce hyperglycemia or worsen hyperinsulinemia but did increase hypertriglyceridemia above 10-week SS. This substantiates the use of 10-week SS as a model of gestational obesity/prediabetes, allowing further studies into treatments of gestational obesity and insulin resistance.

Effects of Melatonin Supplementation on Insulin Levels and Insulin Resistance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2021 ◽  
Vol 53 (09) ◽  
pp. 616-624
Author(s):  
Yan Li ◽  
Zhenbin Xu
Keyword(s):  
Systematic Review ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Model Assessment ◽  
Insulin Levels ◽  
Randomized Controlled

AbstractInsulin resistance (IR) is a pivotal process in various metabolic diseases. The well-known treatment is lifestyle modification and medication therapy, which may result in poor compliance and side effects. Melatonin has been suggested to have a role in glucose metabolism, yet the results across studies have been inconsistent. Therefore, we performed a systematic review to evaluate the effects of melatonin supplementation on insulin levels and IR. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov, and identified randomized controlled trials (RCTs) published prior to August 2020. Articles were reviewed, selected and extracted by two reviewers independently. In total, 8 RCTs of 376 participants were included. Data were pooled using a random-effects model, with mean differences (MDs) and 95% confidence intervals (CIs). Our results showed that melatonin administration significantly reduced insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR), and increased the quantitative insulin sensitivity check index (QUICKI). We conclude that melatonin ameliorated hyperinsulinemia, insulin resistance, and insulin sensitivity, and the results are an update of a previous meta-analysis. Although more investigations are required, we clearly provide evidence for the use of melatonin as an adjuvant treatment for metabolic disorders involving IR.

Abstract 3512: Disruption of Whole Nitric Oxide Synthase System Causes Impaired Glucose Tolerance and Insulin Resistance in Mice in Vivo

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Sei Nakata ◽  
Masato Tsutsui ◽  
Hiroaki Shimokawa ◽  
Ken Sabanai ◽  
Yasuko Yatera ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Pancreatic Islets ◽  
Plasma Glucose ◽  
Insulin Levels

Background : Nitric oxide (NO) synthase (NOS) system consists of 3 different isoforms, including neuronal (nNOS), inducible (iNOS), and endothelial NOSs (eNOS). We have recently succeeded in developing mice lacking all NOS genes (triply n/i/eNOS-KO mice) ( PNAS 2005). Our preliminary study has revealed that the triply-KO mice develop acute myocardial infarction (AMI). The present study was designed to investigate abnormalities of glucose metabolism, an important risk factor of MI, in those mice. Methods and Results : Experiments were performed in 3-month-old male wild-type (WT) and triply-KO mice (n=5–7). At 15 minutes after intravenous glucose administration (1 g/kg), plasma glucose levels (mg/dl) were significantly higher in the triply-KO (475 ± 44) than in the WT mice (241 ± 20) ( P< 0.05), and plasma insulin levels (ng/dl) were significantly lower in the triply-KO (0.50 ± 0.03) than in the WT mice (0.78 ± 0.03) ( P< 0.05). In the triply-KO mice, the size of pancreatic islets (islet/pancreatic area, 0.64 ± 0.16 vs. 2.81 ± 0.64%) was significantly smaller ( P< 0.05), and significant apoptosis of pancreatic islets (apoptotic/total islets, 19 ± 2 vs. 3 ± 1%) (TUNEL staining) was noted as compared with the WT mice ( P< 0.05). Furthermore, insulin sensitivity (as assessed by insulin-induced [ 3 H]-glucose uptake in isolated soleus muscle) (fold increase) was markedly reduced in the triply-KO mice (1.1 ± 0.03) as compared with the WT mice (2.1 ± 0.3) ( P< 0.05), associated with an impairment of insulin-induced translocation of glucose transporter-4 (GLUT-4) to the cellular membrane (immunofluorescent staining) ( P< 0.05). Importantly, supplementation of NO by long-term treatment with isosorbide dinitrate (0.4 mg/day, 6 weeks, dermal application) significantly reversed all these abnormalities of glucose metabolism in the triply-KO mice; plasma glucose (280 ± 28) and insulin levels (0.89 ± 0.10) after glucose tolerance test, insulin sensitivity (1.5 ± 0.08), and GLUT-4 translocation were all improved (all P< 0.05). Conclusions : These results indicate that disruption of whole NOSs system causes impaired glucose tolerance and insulin resistance in mice in vivo, suggesting a critical role of endogenous NO/NOSs system in maintaining glucose metabolism.

Quantification of the relationship between glycemia and β-cell mass adaptation in vivo

2009 ◽  
Vol 87 (8) ◽  
pp. 602-609 ◽  
Author(s):  
Laura L. Atkinson ◽  
Brian G. Topp ◽  
Jenny Au ◽  
Horatiu V. Vinerian ◽  
Narinder Dhatt ◽  
...  
Keyword(s):  
Linear Relationship ◽  
Cell Mass ◽  
Cell Replication ◽  
Sprague Dawley ◽  
Β Cell ◽  
Insulin Levels ◽  
Hyperglycemic Clamp ◽  
Sprague Dawley Rats ◽  
Significant Difference

β-cell mass dynamics play an important role in the adaptation to obesity, as well as in the pathogenesis of type 2 diabetes. Here we used a 24-hour modified hyperglycemic clamp protocol to investigate the effect of increasing glucose concentrations (15, 20, 25, or 35 mmol/L) on β-cell mass and rates of β-cell replication, death, and neogenesis in 6-week-old Sprague Dawley rats (n = 40). During the first 4 h of glucose infusion, plasma insulin levels rose to an approximate steady state in each group, but by the end of 24 h, there was no difference in insulin levels between any of the groups. There was also no difference in β-cell mass between groups. Mean β-cell replication rates displayed a linear relationship to mean plasma glucose levels in all hyperglycemic animals (r2 = 0.98, p < 0.05). Relative to the uninfused basal control animals, replication rates were significantly reduced in the 15 mmol/L glucose group. The percentage of TUNEL-positive β-cells was not different between groups. There was also no significant difference in markers of neogenesis. Thus, these data demonstrate that hyperglycemia for 24 h had no effect on β-cell mass, death, or neogenesis in 6-week-old Sprague Dawley rats. We demonstrate a linear relationship, however, between hyperglycemia and β-cell replication rates in vivo.

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