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Takeshi Ohta - One of the best experts on this subject based on the ideXlab platform.
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Pathological Features of Diabetic Retinopathy in Spontaneously Diabetic Torii Fatty Rats
Journal of diabetes research, 2019Co-Authors: Yoshiaki Tanaka, Tomohiko Sasase, Takeshi Ohta, Rina Takagi, Mina Kobayashi, Fumihiko Toyoda, Machiko Shimmura, Nozomi Kinoshita, Hiroko Takano, Akihiro KakehashiAbstract:Objective. The Spontaneously Diabetic Torii (SDT) Fatty Rat, established by introducing the fa allele (obesity gene) of the Zucker Fatty Rat into the SDT Rat genome, is a new model of obese type 2 diabetes. We studied the pathologic features of diabetic retinopathy (DR) in this animal. Methods. The eyes of SDT Fatty, SDT (controls), and Sprague Dawley (SD) Rats (normal controls) were enucleated at 8, 16, 24, 32, and 40 weeks of age ( for each Rat type at each age). The retinal thicknesses, numbers of retinal folds, and choroidal thicknesses were evaluated. Immunostaining for glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) was performed. Quantitative analyses of the immunopositive regions were performed using a cell-counting algorithm. Results. The retinas tended to be thicker in the SDT Fatty Rats and SDT Rats than in the SD Rats; the choroids tended to be thicker in the SDT Fatty Rats than in the SD Rats. The retinal folds in the SDT Fatty Rats developed earlier and were more severe than in the SDT Rats. Quantitative analyses showed that the GFAP- and VEGF-positive regions in the retinas of the SDT Fatty Rats were significantly larger than those of the SDT Rats. Conclusions. SDT Fatty Rats developed more severe DR earlier than the SDT Rats. The SDT Fatty Rats might be useful as a type 2 diabetes animal model to study DR.
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(SDT Fatty) Rat: A Novel Model of Obese Type 2 Diabetes
2016Co-Authors: Sumiaki Fukuda, Tomohiko Sasase, Katsuhiro Miyajima, Takeshi OhtaAbstract:Abstract: Diabetic animal models play critical roles in the elucidation of the mechanisms of diabetes mellitus and the complications, and in the development of novel drugs as treatments. Spontaneously Diabetic Torii Lepr fa (SDT Fatty) Rat, established by introducing the fa allele of the Zucker Fatty Rat into SDT Rat genome, is a new model of obese type 2 diabetes. We have investigated the characteristics of SDT Fatty Rats. Both male and female SDT Fatty Rats show overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with SDT Rats. With early incidence of diabetes mellitus, diabetic complications in SDT Fatty Rats were seen at younger ages than those in the SDT Rats. Furthermore, we evaluated the pharmacological effects of anti-diabetic drugs, such as metformin, pioglitazone, and dipeptidyl peptidase-4 inhibitor on SDT Fatty Rats. SDT Fatty Rat is a useful model for analysis of metabolic disease and the evaluation of drugs related to metabolic disease
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Metabolic Disorders and Diabetic Complications in Spontaneously Diabetic Torii Leprfa Rat: A New Obese Type 2 Diabetic Model
Journal of diabetes research, 2013Co-Authors: Yusuke Kemmochi, Tomohiko Sasase, Katsuhiro Miyajima, Kenji Fukui, Mimi Maki, Shuichi Kimura, Yukihito Ishii, Takeshi OhtaAbstract:Spontaneously Diabetic Torii Leprfa (SDT Fatty) Rat, established by introducing the fa allele of the Zucker Fatty Rat into SDT Rat genome, is a new model of obese type 2 diabetes. Both male and female SDT Fatty Rats show overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with SDT Rats. With early incidence of diabetes mellitus, diabetic complications, such as nephropathy, retinopathy, and neuropathy, in SDT Fatty Rats were seen at younger ages compared to those in the SDT Rats. In this paper, we overview pathophysiological features in SDT Fatty Rats and also describe new insights regarding the hematology, blood pressure, renal complications, and sexual dysfunction. The SDT Fatty Rats showed an increase of leukocytes, especially the monocyte count, prominent hypertension associated with salt drinking, end-stage renal disease with aging, and hypogonadism. Unlike other diabetic models, the characteristic of SDT Fatty Rat is to present an incidence of diabetes in females, hypertension, and retinopathy. SDT Fatty Rat is a useful model for analysis of various metabolic disorders and the evaluation of drugs related to metabolic disease.
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Diabetic Peripheral Neuropathy in Spontaneously Diabetic Torii-Leprfa (SDT Fatty) Rats
The Journal of veterinary medical science, 2012Co-Authors: Takayuki Yamaguchi, Tomohiko Sasase, Yasuko Mera, Daisuke Tomimoto, Hironobu Tadaki, Yusuke Kemmochi, Takeshi Ohta, Eimei Sato, Mutsuyoshi MatsushitaAbstract:Spontaneously Diabetic Torii (SDT) Rat is a hereditary model of diabetes. Although the SDT Rat shows severe diabetic complications, the onset of hyperglycemia is late. SDT Fatty Rat, established by introducing the fa allele of the Zucker Fatty Rat to SDT Rat, develops diabetes much faster than SDT Rat. In the present study, diabetic peripheral neuropathy (DPN) was evaluated to show the further usefulness of this animal model. Motor nerve conduction velocity (MNCV) was delayed, and the number of sural nerve fibers was decreased in SDT Fatty Rat. Treatment of pioglitazone lowered blood glucose level and prevented delay of MNCV in SDT Fatty Rats. SDT Fatty Rat is a useful animal model for studies of DPN in type 2 diabetes.
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Spontaneously Diabetic Torii Leprfa (SDT Fatty) Rat: A Novel Model of Obese Type 2 Diabetes
The Open Diabetes Journal, 2011Co-Authors: Sumiaki Fukuda, Tomohiko Sasase, Katsuhiro Miyajima, Takeshi OhtaAbstract:Diabetic animal models play critical roles in the elucidation of the mechanisms of diabetes mellitus and the complications, and in the development of novel drugs as treatments. Spontaneously Diabetic Torii Lepr fa (SDT Fatty) Rat, established by introducing the fa allele of the Zucker Fatty Rat into SDT Rat genome, is a new model of obese type 2 diabetes. We have investigated the characteristics of SDT Fatty Rats. Both male and female SDT Fatty Rats show overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with SDT Rats. With early incidence of diabetes mellitus, diabetic complications in SDT Fatty Rats were seen at younger ages than those in the SDT Rats. Furthermore, we evaluated the pharmacological effects of anti-diabetic drugs, such as metformin, pioglitazone, and dipeptidyl peptidase-4 inhibitor on SDT Fatty Rats. SDT Fatty Rat is a useful model for analysis of metabolic disease and the evaluation of drugs related to metabolic disease.
Bradley A. Zinker - One of the best experts on this subject based on the ideXlab platform.
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Endothelin antagonism improves hepatic insulin sensitivity associated with insulin signaling in Zucker Fatty Rats.
Metabolism-clinical and Experimental, 2005Co-Authors: Nathalie Berthiaume, Christian J. Carlson, Cristina M. Rondinone, Bradley A. ZinkerAbstract:Abstract In the present study, we investigated the effects of long-term treatment with the endothelin (ET) antagonist atrasentan, an ET A -selective antagonist, on whole body glucose metabolism and insulin signaling in a commonly used model of insulin resistance, the Zucker Fatty Rat. Zucker lean and Fatty Rats were maintained for 6 weeks on either control or atrasentan-treated water. Euglycemic-hyperinsulinemic clamps (4 mU/kg per minute) were performed at the end of the 6-week treatment on a subset of Rats (n = 10/treatment). In another subset (n = 5/treatment), an insulin tolerance test was performed; liver and muscle tissues were harvested 10 minutes following the challenge for further analysis. Results of the clamps demonstRated that long-term atrasentan treatment significantly increased whole body glucose metabolism in Fatty Rats compared with vehicle control subjects. Insulin-induced insulin receptor substRate 1 tyrosine and protein kinase B serine phosphorylation were significantly reduced in the liver and muscle of Fatty animals compared with their lean littermates. This reduction was overcome with atrasentan treatment in the liver but not in the muscle. There was no difference between lean and Fatty animals, however, in insulin receptor substRate 1 and protein kinase B protein expression in the liver and muscle and no effect by atrasentan. In contrast, expression of the regulatory subunit of PI-3 kinase (p85 α ) was significantly increased in the liver but not in the muscle of Fatty animals compared with their lean littermates and this was normalized to levels of lean animals with atrasentan treatment. These findings indicate that long-standing ET antagonism improves whole body glucose metabolism in Zucker Fatty Rats through improvements in insulin signaling in the liver. These results indicate that therapeutic ET antagonism may assist in correcting the insulin-resistant state.
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Metabolic responses with endothelin antagonism in a model of insulin resistance
Metabolism-clinical and Experimental, 2005Co-Authors: Nathalie Berthiaume, Jerry L. Wessale, Terry J. Opgenorth, Bradley A. ZinkerAbstract:Atrasentan, an endothelin antagonist, would have beneficial effects on metabolic responses in a model of insulin resistance. Zucker lean or Fatty Rats were maintained either on regular (lean and Fatty control, n = 12) or atrasentan-treated water (5 mg/kg/d, Fatty atrasentan, n = 13) for 6 weeks. There was no significant difference in water intake and body weight with the atrasentan-treated group compared with Fatty controls. Although atrasentan had no effect on 3-hour fasting glucose levels, it reduced fasting insulin levels between weeks 2 and 4 of treatment by 53% (Fatty control vs Fatty atrasentan, P < .01). Atrasentan decreased the incremental area under the plasma glucose response curve (ΔAUC) after a nutritionally complete meal tolerance test (MTT), by 28% in the atrasentan-treated group compared with Fatty controls (P < .05), and decreased the MTT-induced insulin ΔAUC by 63% in treated animals compared with the Fatty control group (P < .01). In addition, atrasentan significantly decreased the MTT-induced glucose-insulin index ΔAUC by 58% in treated Rats compared with Fatty controls (P < .01). In summary, in the Zucker Fatty Rat, atrasentan significantly reduces (1) 3-hour fasting insulin levels at 4 weeks, (2) glucose and insulin MTT-induced ΔAUCs, and (3) the MTT-induced glucose-insulin index ΔAUC. These results demonstRate an improvement in hyperinsulinemia as well as in glucose tolerance and insulin sensitivity with chronic endothelin antagonism in a model of insulin resistance and suggest that chronic endothelin antagonism may have benefits in the treatment of insulin resistance and/or diabetes.
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Development of insulin resistance and endothelin-1 levels in the Zucker Fatty Rat.
Metabolism: clinical and experimental, 2003Co-Authors: Nathalie Berthiaume, Amanda K. Mika, Bradley A. ZinkerAbstract:In order to determine the effects of increasing insulin resistance on endothelin-1 (ET-1) levels, Zucker lean and Fatty Rats were studied at basal and during a complete nutrient meal tolerance test (MTT) at 7, 12, and 15 weeks of age. The Fatty Rats were mildly hyperglycemic, severely hyperinsulinemic and glucose-intolerant at all ages versus lean animals and this progressed with age within groups, as previously published. Basal ET-1 levels, at 7 weeks, were significantly increased in Fatty versus lean Rats (3.2 ± 0.5 v 2.0 ± 0.3 pg/mL, respectively; P < .05); however, we did not observe any significant basal difference at 12 or 15 weeks. At 7 weeks, ET-1 levels between Fatty and lean Rats were not different during the MTT (15 minutes: 2.9 ± 0.4 v 2.7 ± 0.7; 120 minutes: 6.5 ± 0.8 v 6.6 ± 0.5 pg/mL, Fatty v lean, respectively). At 12 weeks, though there was no difference in basal levels, Fatty Rats had higher ET-1 levels during the MTT compared to lean animals (15 minutes: 6.9 ± 1.4 v 1.8 ± 0.4; 120 minutes: 9.4 ± 1.7 v 3.2 ± 0.5 pg/mL, respectively; P < .01). At 15 weeks, ET-1 levels during the MTT receded to levels similar to those observed at 7 weeks, which were significantly higher in Fatty versus lean Rats 15 minutes following the challenge (3.4 ± 0.4 v 2.4 ± 0.2 pg/mL, respectively; P < .05). In conclusion, ET-1 levels in the Zucker Fatty Rat: (1) were increased in the early stages of the progression of insulin resistance at 7 weeks, but were unchanged under basal conditions with age thereafter, and (2) were increased under nutrient challenge conditions with advanced insulin resistance up to 12 weeks, and were still significantly but to a lesser degree increased at 15 weeks of age. The explanation for these results and their relationship to the observed insulin resistance is unclear and will require further investigation.
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Metabolic responses in a model of insulin resistance: Comparison between oral glucose and meal tolerance tests
Metabolism: clinical and experimental, 2002Co-Authors: Nathalie Berthiaume, Bradley A. ZinkerAbstract:The purpose of this investigation was to compare the benefits of a meal tolerance test (MTT) against those of an oral glucose tolerance test (OGTT) in one of the most commonly used models of insulin resistance, the Zucker Fatty Rat. Comparison of these two oral challenges will facilitate determination of the most effective means of inducing both glucose and insulin responses in this particular model and allow for possible therapeutic benefits to be examined more effectively. Eight-week-old Zucker Fatty Rats (n = 7 or 8) were used to perform either an OGTT or a MTT following an overnight fast. The OGTT contained a final amount of carbohydRate (CHO) of 1.2 g/kg body weight (BW). The MTT (commercially available liquid meal), in addition to having fat and protein, included a final amount of available CHO and volume to match the OGTT. A saline-treated group served as control. A greater glucose excursion was observed following the OGTT compared to the MTT. The maximal change in glucose from baseline was 140 [plusmn] 10 mg/dL (a 2.1-fold rise) for the OGTT compared to 86.3 [plusmn] 6.1 mg/dL (a 1.7-fold rise) for the MTT (P [lt ] .05). The MTT induced a greater change from baseline in insulin response compared to the OGTT (7.5 [plusmn] 1.1 v 3.9 [plusmn] 0.5 ng/mL, MTT v OGTT, respectively; P [lt ] .05). The saline challenge induced only minimal glucose and insulin responses in comparison to the other treatments. These results suggest that, in a model of insulin resistance, the MTT is a more potent insulin stimulator than glucose alone. A mixed meal, such as a MTT, provides a complete nutrient challenge (CHO, fat, and protein) that will induce both glucose and insulin responses, enabling a better capacity to detect differences in one of the most often used models of insulin resistance, the Zucker Fatty Rat.
Tomohiko Sasase - One of the best experts on this subject based on the ideXlab platform.
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Pathological Features of Diabetic Retinopathy in Spontaneously Diabetic Torii Fatty Rats
Journal of diabetes research, 2019Co-Authors: Yoshiaki Tanaka, Tomohiko Sasase, Takeshi Ohta, Rina Takagi, Mina Kobayashi, Fumihiko Toyoda, Machiko Shimmura, Nozomi Kinoshita, Hiroko Takano, Akihiro KakehashiAbstract:Objective. The Spontaneously Diabetic Torii (SDT) Fatty Rat, established by introducing the fa allele (obesity gene) of the Zucker Fatty Rat into the SDT Rat genome, is a new model of obese type 2 diabetes. We studied the pathologic features of diabetic retinopathy (DR) in this animal. Methods. The eyes of SDT Fatty, SDT (controls), and Sprague Dawley (SD) Rats (normal controls) were enucleated at 8, 16, 24, 32, and 40 weeks of age ( for each Rat type at each age). The retinal thicknesses, numbers of retinal folds, and choroidal thicknesses were evaluated. Immunostaining for glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) was performed. Quantitative analyses of the immunopositive regions were performed using a cell-counting algorithm. Results. The retinas tended to be thicker in the SDT Fatty Rats and SDT Rats than in the SD Rats; the choroids tended to be thicker in the SDT Fatty Rats than in the SD Rats. The retinal folds in the SDT Fatty Rats developed earlier and were more severe than in the SDT Rats. Quantitative analyses showed that the GFAP- and VEGF-positive regions in the retinas of the SDT Fatty Rats were significantly larger than those of the SDT Rats. Conclusions. SDT Fatty Rats developed more severe DR earlier than the SDT Rats. The SDT Fatty Rats might be useful as a type 2 diabetes animal model to study DR.
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(SDT Fatty) Rat: A Novel Model of Obese Type 2 Diabetes
2016Co-Authors: Sumiaki Fukuda, Tomohiko Sasase, Katsuhiro Miyajima, Takeshi OhtaAbstract:Abstract: Diabetic animal models play critical roles in the elucidation of the mechanisms of diabetes mellitus and the complications, and in the development of novel drugs as treatments. Spontaneously Diabetic Torii Lepr fa (SDT Fatty) Rat, established by introducing the fa allele of the Zucker Fatty Rat into SDT Rat genome, is a new model of obese type 2 diabetes. We have investigated the characteristics of SDT Fatty Rats. Both male and female SDT Fatty Rats show overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with SDT Rats. With early incidence of diabetes mellitus, diabetic complications in SDT Fatty Rats were seen at younger ages than those in the SDT Rats. Furthermore, we evaluated the pharmacological effects of anti-diabetic drugs, such as metformin, pioglitazone, and dipeptidyl peptidase-4 inhibitor on SDT Fatty Rats. SDT Fatty Rat is a useful model for analysis of metabolic disease and the evaluation of drugs related to metabolic disease
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Metabolic Disorders and Diabetic Complications in Spontaneously Diabetic Torii Leprfa Rat: A New Obese Type 2 Diabetic Model
Journal of diabetes research, 2013Co-Authors: Yusuke Kemmochi, Tomohiko Sasase, Katsuhiro Miyajima, Kenji Fukui, Mimi Maki, Shuichi Kimura, Yukihito Ishii, Takeshi OhtaAbstract:Spontaneously Diabetic Torii Leprfa (SDT Fatty) Rat, established by introducing the fa allele of the Zucker Fatty Rat into SDT Rat genome, is a new model of obese type 2 diabetes. Both male and female SDT Fatty Rats show overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with SDT Rats. With early incidence of diabetes mellitus, diabetic complications, such as nephropathy, retinopathy, and neuropathy, in SDT Fatty Rats were seen at younger ages compared to those in the SDT Rats. In this paper, we overview pathophysiological features in SDT Fatty Rats and also describe new insights regarding the hematology, blood pressure, renal complications, and sexual dysfunction. The SDT Fatty Rats showed an increase of leukocytes, especially the monocyte count, prominent hypertension associated with salt drinking, end-stage renal disease with aging, and hypogonadism. Unlike other diabetic models, the characteristic of SDT Fatty Rat is to present an incidence of diabetes in females, hypertension, and retinopathy. SDT Fatty Rat is a useful model for analysis of various metabolic disorders and the evaluation of drugs related to metabolic disease.
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Diabetic Peripheral Neuropathy in Spontaneously Diabetic Torii-Leprfa (SDT Fatty) Rats
The Journal of veterinary medical science, 2012Co-Authors: Takayuki Yamaguchi, Tomohiko Sasase, Yasuko Mera, Daisuke Tomimoto, Hironobu Tadaki, Yusuke Kemmochi, Takeshi Ohta, Eimei Sato, Mutsuyoshi MatsushitaAbstract:Spontaneously Diabetic Torii (SDT) Rat is a hereditary model of diabetes. Although the SDT Rat shows severe diabetic complications, the onset of hyperglycemia is late. SDT Fatty Rat, established by introducing the fa allele of the Zucker Fatty Rat to SDT Rat, develops diabetes much faster than SDT Rat. In the present study, diabetic peripheral neuropathy (DPN) was evaluated to show the further usefulness of this animal model. Motor nerve conduction velocity (MNCV) was delayed, and the number of sural nerve fibers was decreased in SDT Fatty Rat. Treatment of pioglitazone lowered blood glucose level and prevented delay of MNCV in SDT Fatty Rats. SDT Fatty Rat is a useful animal model for studies of DPN in type 2 diabetes.
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Spontaneously Diabetic Torii Leprfa (SDT Fatty) Rat: A Novel Model of Obese Type 2 Diabetes
The Open Diabetes Journal, 2011Co-Authors: Sumiaki Fukuda, Tomohiko Sasase, Katsuhiro Miyajima, Takeshi OhtaAbstract:Diabetic animal models play critical roles in the elucidation of the mechanisms of diabetes mellitus and the complications, and in the development of novel drugs as treatments. Spontaneously Diabetic Torii Lepr fa (SDT Fatty) Rat, established by introducing the fa allele of the Zucker Fatty Rat into SDT Rat genome, is a new model of obese type 2 diabetes. We have investigated the characteristics of SDT Fatty Rats. Both male and female SDT Fatty Rats show overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with SDT Rats. With early incidence of diabetes mellitus, diabetic complications in SDT Fatty Rats were seen at younger ages than those in the SDT Rats. Furthermore, we evaluated the pharmacological effects of anti-diabetic drugs, such as metformin, pioglitazone, and dipeptidyl peptidase-4 inhibitor on SDT Fatty Rats. SDT Fatty Rat is a useful model for analysis of metabolic disease and the evaluation of drugs related to metabolic disease.
Francesco Di Nardo - One of the best experts on this subject based on the ideXlab platform.
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ivgtt based simple assessment of glucose tolerance in the Zucker Fatty Rat validation against minimal models
PLOS ONE, 2017Co-Authors: Micaela Morettini, Emanuela Faelli, Sandro Fioretti, Laura Burattini, Piero Ruggeri, Luisa Perasso, Francesco Di NardoAbstract:: 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.
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IVGTT-based simple assessment of glucose tolerance in the Zucker Fatty Rat: Validation against minimal models.
PloS one, 2017Co-Authors: Micaela Morettini, Emanuela Faelli, Sandro Fioretti, Laura Burattini, Piero Ruggeri, Luisa Perasso, Francesco Di NardoAbstract: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
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estimation of second phase insulin secretion in the Zucker Fatty Rat
International Conference of the IEEE Engineering in Medicine and Biology Society, 2016Co-Authors: Micaela Morettini, Francesco Di Nardo, C E Cogo, Emanuela Faelli, Sandro Fioretti, Laura Burattini, Piero RuggeriAbstract: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 (Pearson's 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.
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EMBC - Estimation of second-phase insulin secretion in the Zucker Fatty Rat
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Inte, 2016Co-Authors: Micaela Morettini, Francesco Di Nardo, C E Cogo, Emanuela Faelli, Sandro Fioretti, Laura Burattini, Piero RuggeriAbstract: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 (Pearson's 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.
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c peptide based assessment of insulin secretion in the Zucker Fatty Rat a modelistic study
PLOS ONE, 2015Co-Authors: Francesco Di Nardo, Micaela Morettini, C E Cogo, Emanuela Faelli, Laura Burattini, Piero RuggeriAbstract: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.
Piero Ruggeri - One of the best experts on this subject based on the ideXlab platform.
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ivgtt based simple assessment of glucose tolerance in the Zucker Fatty Rat validation against minimal models
PLOS ONE, 2017Co-Authors: Micaela Morettini, Emanuela Faelli, Sandro Fioretti, Laura Burattini, Piero Ruggeri, Luisa Perasso, Francesco Di NardoAbstract:: 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.
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IVGTT-based simple assessment of glucose tolerance in the Zucker Fatty Rat: Validation against minimal models.
PloS one, 2017Co-Authors: Micaela Morettini, Emanuela Faelli, Sandro Fioretti, Laura Burattini, Piero Ruggeri, Luisa Perasso, Francesco Di NardoAbstract: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
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estimation of second phase insulin secretion in the Zucker Fatty Rat
International Conference of the IEEE Engineering in Medicine and Biology Society, 2016Co-Authors: Micaela Morettini, Francesco Di Nardo, C E Cogo, Emanuela Faelli, Sandro Fioretti, Laura Burattini, Piero RuggeriAbstract: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 (Pearson's 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.
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EMBC - Estimation of second-phase insulin secretion in the Zucker Fatty Rat
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Inte, 2016Co-Authors: Micaela Morettini, Francesco Di Nardo, C E Cogo, Emanuela Faelli, Sandro Fioretti, Laura Burattini, Piero RuggeriAbstract: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 (Pearson's 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.
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c peptide based assessment of insulin secretion in the Zucker Fatty Rat a modelistic study
PLOS ONE, 2015Co-Authors: Francesco Di Nardo, Micaela Morettini, C E Cogo, Emanuela Faelli, Laura Burattini, Piero RuggeriAbstract: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.
