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.

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

Increased skeletal muscle capillarization enhances insulin sensitivity

2014 ◽  
Vol 307 (12) ◽  
pp. E1105-E1116 ◽  
Author(s):  
Thorbjorn Akerstrom ◽  
Lasse Laub ◽  
Kenneth Vedel ◽  
Christian Lehn Brand ◽  
Bente Klarlund Pedersen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Blood Stream ◽  
Whole Body ◽  
Glucose Disposal ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. Therefore, we investigated whether increased skeletal muscle capillarization increases insulin sensitivity. Skeletal muscle-specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist prazosin to the drinking water of Sprague-Dawley rats ( n = 33), whereas 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-wk prazosin treatment, which ensured that prazosin was cleared from the blood stream. Whole body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue-specific insulin sensitivity was assessed by administration of 2-deoxy-[3H]glucose during the plateau phase of the clamp. Whole body insulin sensitivity increased by ∼24%, and insulin-stimulated skeletal muscle 2-deoxy-[3H]glucose disposal increased by ∼30% concomitant with an ∼20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The prazosin treatment did not affect the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point toward the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes.

Abstract 1651: Exercise Improves Aging-associated Myocardial Insulin Resistance by Enhancing Mitochondrial Function in an eNOS Dependent Mechanism

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Qiu X Li ◽  
Quan J Zhang ◽  
Hai F Zhang ◽  
Kun R Zhang ◽  
Jia Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Mitochondrial Function ◽  
Left Ventricular ◽  
Sprague Dawley ◽  
Enos Expression ◽  
Adult Heart ◽  
Aging Heart ◽  
Myocardial Insulin Resistance

Objective . This study sought to determine whether exercise reduces aging-associated myocardial insulin resistance, with a specific focus on the role of eNOS and its relation to mitochondria. Methods . Aging male Sprague-Dawley rats (24 months) were subjected to swim training (60 min/d, 5 d/wk, 9 wk) or assigned as sedentary control. The myocardial contraction, myocardial glucose uptake, mitochondrial function, and eNOS signaling were determined. Results. Aging rats had myocardial insulin resistance as shown by decreased insulin-induced glucose uptake (0.22±0.05 μmol/min/g in aging heart vs.1.29 ± 0.13 μmol/min/g in adult heart, n=8, P <0.01) and attenuated insulin’s positive inotropic role as evidenced by reduced left ventricular developed pressure (90±12 mmHg in aging heart vs. 155±14 mmHg in adult heart, P <0.01). Mitochondrial function was decreased in aging hearts as manifested by the attenuated maximum O 2 consumption by FCCP (1.85±0.39 μmol/min/g in aging hearts vs. 3.72±0.40 μmol/min/g in adult hearts, P <0.01). This was accompanied with the reduced insulin-induced O 2 consumption (1.37±0.31 μmol/min/g in aging heart vs. 2.35±0.31 μmol/min/g in adult heart, P <0.01). In addition, eNOS expression and its phosphorylation by insulin were reduced by 1.2- and 2.3-fold in aging heart, respectively ( P <0.01). Swim training upregulated eNOS expression by 72% ( P <0.01), facilitated eNOS phosphorylation by insulin ( P <0.01), and improved myocardial insulin sensitivity as shown by enhanced glucose uptake by insulin ( P <0.01). Moreover, mitochondrial function was facilitated as manifested by the enhanced O 2 consumption by insulin ( P <0.05), and maximum O 2 consumption ( P <0.01) following swim training. Pretreatment with Cavtratin, an eNOS inhibitor, abolished exercise-improved mitochondrial response to insulin, blocked exercise-improved myocardial insulin sensitivity and the positive inotropic response to insulin in aging heart. Conclusion . These results demonstrate that impaired eNOS signaling and subsequent mitochondrial depression is a major mechanism contributes to aging-associated myocardial insulin resistance, and that exercise improves insulin sensitivity by restoring eNOS signaling and enhancing mitochondrial function.

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.

Gestational postprandial insulin sensitivity in the Sprague Dawley rat: the putative role of hepatic insulin sensitizing substance in glucose partitioning in pregnancy

2020 ◽  
Vol 98 (8) ◽  
pp. 541-547
Author(s):  
Nicole E.J. Lovat ◽  
Dallas J. Legare ◽  
Randall S. Gieni ◽  
W. Wayne Lautt
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Plasma Insulin ◽  
Sprague Dawley ◽  
Fed State ◽  
Triglyceride Concentration ◽  
Insulin Dependent ◽  
Postprandial Insulin ◽  
Glucose Partitioning ◽  
In Pregnancy

Pregnancy requires adaptation of maternal insulin sensitivity. In the fed state, a pulse of insulin stimulates glucose uptake and nutrient energy storage via insulin-dependent as well as hepatic insulin sensitizing substance (HISS)-dependent action. HISS is released by the liver in the fed state in the presence of signals integrated through the liver and a pulse of insulin. HISS promotes glucose storage as glycogen in heart, kidney, and skeletal muscle but not in gut, liver, or adipose tissue. HISS is also responsible for the vasodilatory action previously attributed to insulin. The rapid insulin sensitivity test (RIST), a dynamic euglycemic clamp, can quantitate both HISS-dependent and insulin-dependent glucose uptake. The RIST was used to characterize postprandial insulin sensitivity in the Sprague Dawley rat and the changes in the partitioning of nutrient energy throughout gestation. Early pregnancy demonstrated increased insulin sensitivity attributable to HISS-dependent glucose uptake with unchanged insulin-dependent glucose uptake, preserved plasma insulin concentration, and reduced plasma triglyceride concentration compared to the virgin. In late pregnancy, there was reduced HISS-dependent and insulin-dependent glucose uptake accompanied by increased plasma insulin and triglyceride concentration compared to the virgin. These results suggest an important role for HISS in glucose partitioning in pregnancy.

Ultrastructural investigation of spontaneous pituitary gonadotroph cell adenomas in aging Sprague-Dawley rats

1983 ◽  
Vol 41 ◽  
pp. 702-703
Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs
Keyword(s):  
Electron Microscopy ◽  
Animal Model ◽  
Epoxy Resin ◽  
Immunoelectron Microscopy ◽  
Tumor Type ◽  
Gonadal Function ◽  
Sprague Dawley ◽  
Male And Female ◽  
Reticulin Fibers ◽  
Sprague Dawley Rats

Gonadotroph cell adenomas of the pituitary are infrequent in human patients and are not invariably associated with altered gonadal function. To date, no animal model of this tumor type exists. Herein, we describe spontaneous gonadotroph cell adenomas in old male and female Sprague-Dawley rats by histology, immunocytology and electron microscopy.The material consisted of the pituitaries of 27 male and 38 female Sprague Dawley rats, all 26 months of age or older, removed at routine autopsy. Sections of formal in-fixed, paraffin-embedded tissue were stained with hematoxylin-phloxine-saffron (HPS), the PAS method and the Gordon-Sweet technique for the demonstration of reticulin fibers. For immunostaining, sections were exposed to anti-rat β-LH, anti-ratβ-TSH, anti-rat PRL, anti-rat GH and anti-rat ACTH 1-39. For electron microscopy, tissue was fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4 and embedded in epoxy-resin. Tissue fixed in 10% formalin, embedded in epoxy resin without osmification, was used for immunoelectron microscopy.

Abstract 1361: Leukocyte Antigen-Related Phosphatase Regulates Insulin Sensitivity by Interaction with Snapin

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Aleksandr E Vendrov ◽  
Igor Tchivilev ◽  
Xi-Lin Niu ◽  
Juxiang Li ◽  
Marschall S Runge ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glycogen Synthase ◽  
Serine Phosphorylation ◽  
Snare Complex ◽  
Vascular Pathology ◽  
Wild Type ◽  
Membrane Translocation ◽  
Leukocyte Antigen

Several protein tyrosine phosphatases including leukocyte antigen-related (LAR) phosphatase have been implicated in insulin resistance, which is a risk factor for atherosclerosis. We showed previously that LAR negatively regulates insulin-like growth factor-1 (IGF1) signaling in vascular smooth muscle cells (VSMC) leading to increased proliferation and migration. Absence of LAR also enhanced neointima formation in response to arterial injury in mice. However, the role of LAR-modulated signaling in the development of insulin resistance has not been elucidated. Here, we investigated the function of LAR in regulating glucose uptake and insulin sensitivity. We identified snapin, a SNARE-associated protein involved in glucose transporter Glut4 vesicle fusion with plasma membrane, as a LAR-interacting protein using a yeast two-hybrid screen. IGF1-induced serine phosphorylation of snapin, its translocation to membrane and association with SNARE complex were enhanced in VSMC lacking LAR. Similarly, PI3K-PDK1-PKCζ signaling pathway was more active in LAR-/- cells after IGF1 treatment. This resulted in enhanced Glut4 activation, its membrane translocation and association with snapin. Glut4 membrane translocation and association with snapin after IGF1 treatment were impaired in snapin+/− VSMC. IGF1 treatment also increased serine phosphorylation of GSK3 β in LAR−/− VSMC leading to increased activation of glycogen synthase. Consistent with this, enhanced glucose uptake was observed in LAR−/− VSMC compared to wild-type cells after IGF1 treatment. Basal and IGF1-induced glucose uptake were significantly lower in snapin+/− VSMC than in wild-type cells. Snapin+/− mice had higher levels of blood glucose, lower quantitative insulin sensitivity check index (QUICKI) and impaired response to insulin in insulin tolerance test (ITT) compared to wild-type mice. Decrease of QUICKI and impairment of IIT were more pronounced in snapin+/− mice fed a high-fat diet. In addition, Doppler ultrasonography indicated increased arterial stiffness in snapin+/− mice. Together, these data indicate that LAR negatively regulates snapin phosphorylation which in turn affects glucose uptake leading to the development of insulin resistance and vascular pathology.

The prophylactic potential of Zingiber officinale flowers and leaves extract to mitigate hyperglycemia in Sprague Dawley rats

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Saira Tanweer ◽  
Tariq Mehmood ◽  
Saadia Zainab ◽  
Zulfiqar Ahmad ◽  
Muhammad Ammar Khan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Zingiber Officinale ◽  
Sprague Dawley ◽  
Content Type ◽  
Sprague Dawley Rats ◽  
Hematological Analysis ◽  
Therapeutic Tools

Purpose Innovative health-promoting approaches of the era have verified phytoceutics as one of the prime therapeutic tools to alleviate numerous health-related ailments. The purpose of this paper is to probe the nutraceutic potential of ginger flowers and leaves against hyperglycemia. Design/methodology/approach The aqueous extracts of ginger flowers and leaves were observed on Sprague Dawley rats for 8 weeks. Two parallel studies were carried out based on dietary regimes: control and hyperglycemic diets. At the end of the experimental modus, the overnight fed rats were killed to determine the concentration of glucose and insulin in serum. The insulin resistance and insulin secretions were also calculated by formulae by considering fasting glucose and fasting insulin concentrations. Furthermore, the feed and drink intakes, body weight gain and hematological analysis were also carried out. Findings In streptozotocin-induced hyperglycemic rats, the ginger flowers extract depicted 5.62% reduction; however, ginger leaves extract reduced the glucose concentration up to 7.11% (p = 0.001). Similarly, ginger flowers extract uplifted the insulin concentration up to 3.07%, while, by ginger leaves extract, the insulin value increased to 4.11% (p = 0.002). For the insulin resistance, the ginger flower showed 5.32% decrease; however, the insulin resistance was reduced to 6.48% by ginger leaves (p = 0.014). Moreover, the insulin secretion increased to 18.9% by flower extract and 21.8% by ginger leave extract (p = 0.001). The feed intake and body weight gain increased momentously by the addition of ginger flowers and leaves; however, the drink intake and hematological analysis remained non-significant by the addition of ginger parts. Originality/value Conclusively, it was revealed that leaves have more hypoglycemic potential as compared to flowers.

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