Emanuela Faelli

Postural control after a strenuous treadmill exercise

The effect of a strenuous treadmill exercise on body stability and the mechanisms associated with it have been studied with two different experimental protocols. The former investigation was based on stabilometric and metabolic measurements performed in basal condition and after a strenuous treadmill exercise whilst the latter dealt with the study of the early postural response to a 3s-bilateral soleus muscle vibration after the strenuous exercise. Our exercise protocol was able to induce an important generalized metabolic fatigue, as assessed by the obtained peak values in the measured metabolic parameters, and resulting in a short-lasting body destabilization. A linear relationship between sway path and oxygen uptake was found. Thus, the short duration of body instability could be likely due to the quite rapid recovery of oxygen uptake. Further, the fatigue-induced body instability did not associate with changes in the early postural response to soleus muscle vibration. The present study cannot rule out the possibility that further central and/or peripheral mechanisms, influencing the postural control, may play a role in the fatigue-induced changes in body sway.

Age‐related analysis of insulin resistance, body weight and arterial pressure in the Zucker fatty rat

The evolution with ageing of insulin resistance, body weight (BW) and mean arterial pressure (MAP) was studied in a group of Zucker fatty rats (ZFRs, n= 22), between 7 and 16 weeks of age, compared with an age‐matched control group of Zucker lean rats (ZLRs, n= 22). The minimal model of glucose kinetics was applied to estimate glucose effectiveness, SG, and insulin sensitivity, SI, from insulinaemia and glycaemia measured during a 70 min intravenous glucose tolerance test. No correlation was found between SG and age in both ZFR and ZLR groups. No significant changes in mean SG between the two groups indicated no alteration of glucose‐mediated glucose disposal. Estimates of SI from individual ZFRs were independent of age and, on average, showed 83% reduction (P < 0.001) compared with the ZLR group. Despite the lack of alteration of SI with age, the ZFR group showed an age‐related increase of MAP, which correlated with increasing BW (r = 0.71 and P < 0.001). These results support the hypothesis that in our ZFRs, as a suitable genetic model of obesity and hypertension, insulin resistance is fully established at the age of 7 weeks and remains practically unaltered until at least the sixteenth week. An age‐related increase in arterial pressure, observed in this strain, relates more properly to increasing BW, rather than insulin resistance. Development of hypertension with increasing age and BW may result from an enhanced insulin‐mediated activity of the sympathetic nervous system, as observed in our previously reported study.

C-Peptide-based assessment of insulin secretion in the Zucker Fatty rat: a modelistic study.

A C-peptide-based assessment of β-cell function was performed here in the Zucker fatty rat, a suitable animal model of human metabolic syndrome. To this aim, a 90-min intravenous glucose tolerance test (IVGTT) was performed in seven Zucker fatty rats (ZFR), 7-to-9week-old, and seven age-matched Zucker lean rats (ZLR). The minimal model of C-peptide (CPMM), originally introduced for humans, was adapted to Zucker rats and then applied to interpret IVGTT data. For a comprehensive evaluation of glucose tolerance in ZFR, CPMM was applied in combination with the minimal model of glucose kinetics (GKMM). Our results showed that the present CPMM-based interpretation of data is able to: 1) provide a suitable fit of C-Peptide data; 2) achieve a satisfactory estimation of parameters of interest 3) quantify both insulin secretion by estimating the time course of pre-hepatic secretion rate, SR(t), and total insulin secretion, TIS, and pancreatic sensitivity by means of three specific indexes of β-cell responsiveness to glucose stimulus (first-phase, Ф1, second-phase, Ф2, and steady-state, Фss, never assessed in Zucker rats before; 4) detect the significant enhancement of insulin secretion in the ZFR, in face of a severe insulin-resistant state, previously observed only using a purely experimental approach. Thus, the methodology presented here represents a reliable tool to assess β-cell function in the Zucker rat, and opens new possibilities for the quantification of further processes involved in glucose homeostasis such as the hepatic insulin degradation.

IVGTT-based simple assessment of glucose tolerance in the Zucker fatty rat: Validation against minimal models

For the assessment of glucose tolerance from IVGTT data in Zucker rat, minimal model methodology is reliable but time- and money-consuming. This study aimed to validate for the first time in Zucker rat, simple surrogate indexes of insulin sensitivity and secretion against the glucose-minimal-model insulin sensitivity index (SI) and against first- (Φ1) and second-phase (Φ2) β-cell responsiveness indexes provided by C-peptide minimal model. Validation of the surrogate insulin sensitivity index (ISI) and of two sets of coupled insulin-based indexes for insulin secretion, differing from the cut-off point between phases (FPIR3-SPIR3, t = 3 min and FPIR5-SPIR5, t = 5 min), was carried out in a population of ten Zucker fatty rats (ZFR) and ten Zucker lean rats (ZLR). Considering the whole rat population (ZLR+ZFR), ISI showed a significant strong correlation with SI (Spearman’s correlation coefficient, r = 0.88; P<0.001). Both FPIR3 and FPIR5 showed a significant (P<0.001) strong correlation with Φ1 (r = 0.76 and r = 0.75, respectively). Both SPIR3 and SPIR5 showed a significant (P<0.001) strong correlation with Φ2 (r = 0.85 and r = 0.83, respectively). ISI is able to detect (P<0.001) the well-recognized reduction in insulin sensitivity in ZFRs, compared to ZLRs. The insulin-based indexes of insulin secretion are able to detect in ZFRs (P<0.001) the compensatory increase of first- and second-phase secretion, associated to the insulin-resistant state. The ability of the surrogate indexes in describing glucose tolerance in the ZFRs was confirmed by the Disposition Index analysis. The model-based validation performed in the present study supports the utilization of low-cost, insulin-based indexes for the assessment of glucose tolerance in Zucker rat, reliable animal model of human metabolic syndrome.

Calpain-1 resident in lipid raft/caveolin-1 membrane microdomains plays a protective role in endothelial cells

We are here reporting that calpain-1 is a constitutive component of a distinct lipid raft/caveolin-1 microdomain isolated from bEnd5 cells in association with endothelial nitric oxide synthase (eNOS) and heat shock protein 90 (HSP90). Perturbations in intracellular calcium concentration by Ca2+-ionophore A23187 or prolonged cell exposure to high glucose induce a significant decrease in the level of eNOS accompanied by a recruitment of additional HSP90 molecules at this site. In these conditions the cells are more resistant to cell death by Ca2+ overload. The decrease of eNOS has been due not only to its Ca2+-mediated release from the caveolin-1 aggregates but also to its digestion by calpain-1. The specific involvement of calpain-1 in digestion of eNOS is supported by the preventive effect of a synthetic calpain inhibitor (CI-2) and by the absence of calpain-2 and calpastatin in the caveolin-1 microdomain. These results suggest that the protein adjustments observed in lipid raft/caveolin-1 microdomains could be visualized as a process required to protect the cells against NO overproduction and aberrant calpain activation. Alterations in eNOS, calpain-1 and HSP90 levels have been observed in aorta of Zucker Diabetic Rats (ZDR). The loss of HSP90 occurring in these animals indicates an aberrant activation of calpain and thereby the transition from a physiological to a pathological cell condition.

Sensorimotor Skills Impact on Temporal Expectation: Evidence from Swimmers

Aim of this study was to assess whether the ability to predict the temporal outcome of a sport action was influenced by the sensorimotor skills previously acquired during a specific sport training. Four groups, each of 30 subjects, were enrolled in this study; subjects of three groups practiced different sports disciplines (i.e., swimming, rhythmic gymnastics, and water polo) at competitive level whilst the fourth group consisted of control subjects. Subjects were asked to observe a video showing a swimmer doing two laps in crawl style. This video was shown 36 times, and was occluded after variable intervals, randomized across trials, by a dark window that started 3, 6, and 12 s before the swimmer touched the poolside. During the occluded interval, subjects were asked to indicate when the swimmer touched the edge of the pool by clicking on any button of the laptop keyboard. We found that swimmers were more accurate than subjects performing other sports in temporally predicting the final outcome of the swimming task. Particularly, we observed a significant difference in absolute timing error that was lower in swimmers compared to other groups when they were asked to make a temporal prediction with the occluded interval of short duration (i.e., 3 s). Our findings demonstrate that the ability to extract temporal patterns of a motor action depends largely on the subjective expertise, suggesting that sport-acquired sensorimotor skills impact on the temporal representation of the previously observed action, allowing subjects to predict the time course of the action in absence of visual information.

Estimation of second-phase insulin secretion in the Zucker fatty rat

The purpose of the present study was to test the efficacy of the empiric index SPIR (Second-phase Insulin Release) in the quantification of second-phase insulin secretion in the Zucker Fatty Rat. SPIR index is defined as the area under the curve of insulin between 8 and 90 min after an Intravenous Glucose Tolerance Test (IVGTT). The validation of such index was performed against the second-phase β-cell responsiveness index (Φ 2 ) provided by C-peptide minimal model. To this aim, Φ 2 and SPIR were simultaneously computed from IVGTT data, measured in six Zucker fatty rats (ZFR), 7-to-9week-old, and seven age-matched Zucker lean rats (ZLR). SPIR index showed a significant linear correlation with Φ 2 (Pearsons correlation coefficient, r = 0.91, R-square = 0.82, P 2 (P 2 , in the evaluation of the second-phase insulin secretion and of its alteration in Zucker Fatty Rats. Thus, the study proposes the SPIR, as a suitable index for a simple, reliable and low-cost quantification of the second-phase insulin secretion in ZFR.

Simple Assessment of Insulin Sensitivity in the Zucker Rat

The model-based assessment of insulin sensitivity in Zucker rat from Intravenous Glucose Tolerance Test (IVGTT) data is a common procedure. The minimal model methodology provides a very reliable assessment but requires specific competence for running the model. The aim of this study was presenting calculated SI (CSI), as a surrogate index for the simple assessment of insulin sensitivity in the Zucker Rat from IVGTT data. To this aim 25 Zucker Lean Rats (ZLR) and 25 Zucker Fatty Rats (ZFR) were considered. Reference insulin sensitivity (SI) was estimated in each rat through the minimal model methodology. CSI is defined as the ratio between the rate of glucose disappearance (KG) and the mean supra-basal area under the insulin curve during the test (ΔAUCINS), corrected by the proportionality term, α. Regression analysis between SI and KG/ΔAUCINS was performed to identify the α coefficient. Results showed as the computed value of CSI presented a high correlation (r = 0.89, R-square = 0.80 and p < 0.0001, slope ≈1) with SI. Mean value of CSI over the whole population was not significantly different from correspondent SI value (p = 0.17). CSI is able to detect the wellknown reduction of insulin sensitivity in the ZFR group (1.0±0.1 vs. 5.0±0.7 min-1/μU·ml-1, p < 0.001), in accordance with the results provided by SI. In conclusion, the present study proposes CSI, as a suitable empiric index for a simple and reliable assessment of insulin sensitivity in Zucker rat and able to provide the same quantitative information of modelbased SI.

The Relative Role of Insulin Action and Secretion in Experimental Animal Models of Metabolic Syndrome

In the present study we evaluated insulin action and secretion in a group of 7 young Zucker fatty rats (ZFR), and in a group of 8 spontaneously hypertensive rats (SHR), compared with two control groups of 7 young Zucker lean rats (ZLR) and 8 Wistar Kyoto rats (WKY), respectively. Our goal is to broaden the characterization of glucose tolerance, including insulin secretion, in two animal models used for the characterization of human metabolic syndrome: the ZFR and the SHR. Reliable estimates of insulin sensitivity index, SI, was provided by minimal model analysis of IVGTT data. To characterize insulin secretion we calculated an index based on IVGTT data: AIRG, i.e. the acute insulin response after glucose bolus, related to the first phase insulin secretion. The ZFR showed a significantly (p<0.005) lower mean estimate of SI, and a significantly (p<0.001) higher mean value of AIRG, compared to control groups (ZLR and WKY) and hypertensive rats (SHR). Thus, only the ZFR shows a reduced insulin action, compensated only partially by insulin hypersecretion. This suggests obesity, with respect to hypertension, as a primary factor in the deterioration of glucose tolerance.