Aging does not contribute to the decline in insulin  action on storage of muscle glycogen in rats

Gupta, Gaurav; She, Li; Xi, Hui; Yang, Xiao Man; Hu, Meizhu; Cases, Jane A.; Vuguin, Patricia; Rossetti, Luciano; Barzilai, Nir

doi:10.1152/ajpregu.2000.278.1.r111

Cited by 25 publications

(27 citation statements)

References 31 publications

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“…Significant reductions of AT observed in this study in the aging group are consistent with previous results (15) obtained in similarly aged Sprague-Dawley rats. However, significant reductions of lean body mass, also seen in the aging group in this study, were not observed in three previous studies (6,7,12) of age-related changes of body composition in similarly aged rats. This may be due to the fact that different strains of rat were used in each of the studies considered.…”

Section: Treatment Effects On Body Compositioncontrasting

confidence: 92%

High-resolution magnetic resonance imaging tracks changes in organ and tissue mass in obese and aging rats

Tang

Vasselli

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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Tang, Haiying, Joseph R. Vasselli, Ed X. Wu, Carol N. Boozer, and Dympna Gallagher. High-resolution magnetic resonance imaging tracks changes in organ and tissue mass in obese and aging rats. Am J Physiol Regulatory Integrative Comp Physiol 282: R890-R899, 2002. First published November 8, 2001 10.1152/ajpregu.0527.2001.-Magnetic resonance imaging (MRI) has the ability to discriminate between various soft tissues in vivo. Whole body, specific organ, total adipose tissue (TAT), intra-abdominal adipose tissue (IAAT), and skeletal muscle (SM) weights determined by MRI were compared with weights determined by dissection and chemical analysis in two studies with male SpragueDawley rats. A 4.2-T MRI machine acquired high-resolution, in vivo, longitudinal whole body images of rats as they developed obesity or aged. Weights of the whole body and specific tissues were determined using computer image analysis software, including semiautomatic segmentation algorithms for volume calculations. High correlations were found for body weight (r ϭ 0.98), TAT (r ϭ 0.99), and IAAT (r ϭ 0.98) between MRI and dissection and chemical analyses. MRI estimated the weight of the brain, kidneys, and spleen with high accuracy (r Ͼ 0.9), but overestimated IAAT, SM, and liver volumes. No differences were detected in organ weights using MRI and dissection measurements. Longitudinal MRI measurements made during the development of obesity and aging accurately represented changes in organ and tissue mass.longitudinal body composition; in vivo; obesity; high-fat diet; small animal THE ACCURATE MEASUREMENT OF body compartments is important in the study of obesity and other diseases. There are many techniques available for body composition measurement, including hydrodensitometry, anthropometry, computerized tomography (CT), and dual-energy X-ray absorptiometry (14). Magnetic resonance imaging (MRI) and CT have been applied in the measurement of total and regional human and animal body composition (10,22,25). However, limitations associated with ionizing radiation in CT have made MRI a more desirable method for human body composition assessment, since it provides a safe, noninvasive, in vivo measurement approach (3).To evaluate the accuracy and validate the viability of MRI as a means of measuring body composition in rodents, Ross et al. (22) tested a model using MRI to measure adipose tissue (AT) and skeletal muscle (SM) volumes in rats. MRI-derived AT volumes were compared with those obtained by CT and chemical analysis in rats. The results (22) showed highly significant correlation coefficients among these methods without systematic differences, thereby demonstrating that MRI and CT assess AT volume with a comparable level of accuracy compared with chemical analysis in rats. Fowler et al. (10) reported that MRI accurately measured AT in lean and obese pigs in vivo, and Ishikawa and Koga (13) proposed an animal model of non-insulin-dependent diabetes mellitus for the accurate measurement of abdominal fat in Otsuka Long-Evans Tokushima fatty rats ...

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Section: Treatment Effects On Body Compositioncontrasting

confidence: 92%

High-resolution magnetic resonance imaging tracks changes in organ and tissue mass in obese and aging rats

Tang

Vasselli

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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“…All rats were fed ad libitum using regular rat diet that consisted of 64% carbohydrate, 30% protein, and 6% fat, with a physiological fuel value of 3.3 kcal/g food. At 1 week before the in vivo study, rats were anesthetized by inhalation of methoxyflurane, and indwelling catheters were inserted in the right internal jugular vein and left carotid artery (22)(23)(24)(25)(26). This method of anesthesia allows fast recovery and normal food consumption after 1 day.…”

Section: Methodsmentioning

confidence: 99%

“…Body composition was assessed as described earlier (22)(23)(24)(25)(26). Briefly, rats received an intra-arterial bolus injection of 20 Ci of tritiated-labeled water ( 3 H 2 O; Du Pont-NEN, Boston, MA), and plasma samples were obtained at 30-min intervals for 3 h. Steady-state conditions for plasma 3 H 2 O-specific activity were achieved within 45 min in all studies.…”

Section: Methodsmentioning

confidence: 99%

“…To mimic components of in vivo physiological postmeal conditions, the following protocols were designed: 1) a saline study, in which saline was infused into rats for 3 h, and 2) a hyperinsulinemic-euglycemic clamp study. Rats received a primed continuous insulin infusion (3 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ) to obtain physiological, postmeal insulin levels and a variable infusion of dextrose (25%), periodically adjusted to clamp the plasma glucose concentration at the basal level for the 2 h of the clamp (22)(23)(24)(25)(26). A primed, continuous infusion of high-performance liquid chromatographyϪpurified [ 3 H-3]glucose (Du Pont-NEN; 15-40 Ci bolus, followed by 0.4 Ci/min infusion) was initiated at t ϭ 0 and maintained for 4 h. At the end of the clamp study, rats were killed using 60 mg pentobarbital sodium/kg body wt.…”

Section: Methodsmentioning

confidence: 99%

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Hepatic Insulin Resistance Precedes the Development of Diabetes in a Model of Intrauterine Growth Retardation

et al. 2004

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Intrauterine growth retardation (IUGR) has been linked to the development of type 2 diabetes in adulthood. We developed an IUGR model in rats whereby at age 3-6 months the animals develop a diabetes that is associated with insulin resistance. Hyperinsulinemiceuglycemic clamp studies were performed at age 8 weeks, before the onset of obesity and diabetes. Basal hepatic glucose production (HGP) was significantly higher in IUGR than in control rats (14.6 ؎ 0.4 vs. 12.3 ؎ 0.3 mg ⅐ kg ؊1 ⅐ min ؊1 ; P < 0.05). Insulin suppression of HGP was blunted in IUGR versus control rats (10.4 ؎ 0.6 vs. 6.5 ؎ 1.0 mg ⅐ kg ؊1 ⅐ min ؊1 ; P < 0.01); however, rates of glucose uptake and glycogenolysis were similar between the two groups. Insulin-stimulated insulin receptor substrate 2 and Akt-2 phosphorylation were significantly blunted in IUGR rats. PEPCK and glucose-6-phosphatase mRNA levels were increased at least threefold in liver of IUGR compared with control rats. These studies suggest that an aberrant intrauterine milieu permanently impairs insulin signaling in the liver so that gluconeogenesis is augmented in the IUGR rat. These processes occur early in life, before the onset of hyperglycemia, and indicate that uteroplacental insufficiency causes a primary defect in gene expression and hepatic metabolism that leads to the eventual development of overt hyperglycemia. Diabetes 53:2617-2622, 2004 U teroplacental insufficiency limits the availability of substrates to the fetus and retards growth during gestation (1,2). We have previously shown that this abnormal metabolic intrauterine milieu affects the development of the fetus by modifying the gene expression and function of susceptible cells in the pancreas, muscle, and liver (3-5). The end result is the development of type 2 diabetes in adulthood (4). The unique feature of our animal model of intrauterine growth retardation (IUGR) is its ability to induce diabetes in adult rats with the salient features of most forms of type 2 diabetes in humans, that is, defects in insulin action and insulin secretion. IUGR animals exhibit insulin resistance early in life (before the onset of hyperglycemia) that is characterized by blunted whole-body glucose disposal in response to insulin (4).The liver plays an important role in maintaining blood glucose homeostasis by controlling hepatic glucose production (HGP) (6,7). In type 2 diabetes, the high levels of HGP and the inability of insulin to adequately suppress hepatic glucose output are major contributors to both fasting hyperglycemia and exaggerated postprandial hyperglycemia (8 -14).Insulin resistance is associated with a postreceptor defect(s) in the intracellular insulin-signaling cascade, leading to the failure of insulin to suppress HGP (15). Insulin binds to its receptor, which leads to activation of the insulin receptor, insulin receptor substrates (IRSs) such as IRS-1 and -2, phosphatidylinositol 3-kinase, and Akt. Akt activation leads to decreased transcription of PEPCK and glucose-6-phosphatase (G6Pase) (16), thus reducing gluc...

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“…Glucose clamp procedures were performed in awake, precatheterized, unrestrained, unanesthetized rats as described (7,9,10). Briefly, rats were fasted for 6 h, and a 2-h hyperinsulinemic euglycemic clamp procedure was conducted.…”

Section: Rat Models Usedmentioning

confidence: 99%

Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats

Muniyappa

Chen

Muzumdar

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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The hyperinsulinemic euglycemic glucose clamp, the reference standard for measuring insulin sensitivity in humans and animals, is labor intensive and technically demanding. A number of simple surrogate indexes of insulin sensitivity/resistance have been developed and validated primarily for use in large human studies. These same surrogates are also frequently used in rodent studies. However, in general, these indexes have not been rigorously evaluated in animals. In a recent validation study in mice, we demonstrated that surrogates have a weaker correlation with glucose clamp estimates of insulin sensitivity/resistance than in humans. This may be due to increased technical difficulties in mice and/or intrinsic differences between human and rodent physiology. To help distinguish among these possibilities, in the present study, using data from rats substantially larger than mice, we compared the clamp glucose infusion rate (GIR) with surrogate indexes, including QUICKI, HOMA, 1/HOMA, log (HOMA), and 1/fasting insulin. All surrogates were modestly correlated with GIR (r ϭ 0.34 -0.40). Calibration analyses of surrogates adjusted for body weight demonstrated similar predictive accuracy for GIR among all surrogates. We conclude that linear correlations of surrogate indexes with clamp estimates and predictive accuracy of surrogate indexes in rats are similar to those in mice (but not as substantial as in humans). This additional rat study (taken with the previous mouse study) suggests that application of surrogate insulin sensitivity indexes developed for humans may not be appropriate for determining primary outcomes in rodent studies due to intrinsic differences in metabolic physiology. However, use of surrogates may be appropriate in rodents, where feasibility of clamps is an obstacle and measurement of insulin sensitivity is a secondary outcome. glucose clamp; calibration model; quantitative insulin-sensitivity check index INSULIN RESISTANCE IS TYPICALLY DEFINED as decreased sensitivity and/or responsiveness to metabolic actions of insulin (19). This cardinal feature of diabetes, obesity, and dyslipidemias is also a prominent component of cardiovascular diseases, including hypertension, coronary heart disease, and atherosclerosis (6, 26). Rodent models of metabolic diseases and their cardiovascular complications are useful for elucidating underlying pathophysiology and for evaluating novel therapeutic approaches (5, 12, 22). The ability to efficiently and accurately quantify insulin sensitivity/resistance is an essential aspect of ascertaining the metabolic phenotype of rodent models of human diseases and their response to therapeutic interventions. In both humans and animals, the reference standard method for directly quantifying insulin sensitivity/resistance is the hyperinsulinemic euglycemic glucose clamp (19). This is a technically demanding, time-consuming procedure that is not feasible to apply in large studies. Therefore, more tractable surrogate indexes of insulin sensitivity/resistance have been developed ...

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Aging does not contribute to the decline in insulin action on storage of muscle glycogen in rats

Cited by 25 publications

References 31 publications

High-resolution magnetic resonance imaging tracks changes in organ and tissue mass in obese and aging rats

High-resolution magnetic resonance imaging tracks changes in organ and tissue mass in obese and aging rats

Hepatic Insulin Resistance Precedes the Development of Diabetes in a Model of Intrauterine Growth Retardation

Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats

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