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

Di Nardo F, Cogo CE, Faelli E, Morettini M, Burattini L, Ruggeri P - PLoS ONE (2015)

Bottom Line: 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, Ф(1), second-phase, Ф(2), and steady-state, Ф(ss), 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy.

ABSTRACT
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-9 week-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, Ф(1), second-phase, Ф(2), and steady-state, Ф(ss), 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.

No MeSH data available.


Related in: MedlinePlus

Time course of above steady-state insulin secretion rate, SR(t), during 90-min IVGTT in our ZFR group (n = 7, closed circles) and ZLR group (n = 7, open circles).Values are mean ± SE.
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pone.0125252.g004: Time course of above steady-state insulin secretion rate, SR(t), during 90-min IVGTT in our ZFR group (n = 7, closed circles) and ZLR group (n = 7, open circles).Values are mean ± SE.

Mentions: Quantification of β-cell function was achieved by the interpretation of C-peptide data by the minimal model of C-peptide secretion (CPMM). CPMM provided a good fit to C-peptide data, as judged from the average weighted residuals (over all fourteen rats, Fig 3) which showed no systematic deviation from zero and were within the range [-1, +1]. This behavior is consistent with the hypothesis that the measurement error was a random variable normally distributed, around zero. Estimates of main CPMM parameters and steady-state indexes in individual rats are given in Table 2 for ZLRs and ZFRs. Precision is given in parentheses. The individual estimates of the other model parameters have been reported in S1 Table. A significant difference in mean estimates of Φ1 (116%, Fig 2B), Φ2 (418%, Fig 2C) and Φss (927%) was detected in the ZFR group, compared with the ZLR group, indicating an overall enhanced responsiveness of β-cell secretion to glucose stimulus. Mean steady-state secretion rate, SRss (min-1·pmol/L), was significantly higher in the ZFR group (498±85) compared to the ZLR group (47.8±9.6). Mean above steady-state secretion rate, SR(t), showed a significant increase in our ZFR group, between 0 and 25 min (Fig 4). Thus, total insulin secretion rate TSR(t) (TSR(t) = SR(t) + SRSS, see Eq A8 in the Appendix 1), was significantly higher in the ZFR group throughout the entire IVGTT. Integration of TSR(t), over 90 min yielded a significant 761% increase in total insulin secretion per unit of distribution volume, TIS, in the ZFR group (Fig 2D).


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

Di Nardo F, Cogo CE, Faelli E, Morettini M, Burattini L, Ruggeri P - PLoS ONE (2015)

Time course of above steady-state insulin secretion rate, SR(t), during 90-min IVGTT in our ZFR group (n = 7, closed circles) and ZLR group (n = 7, open circles).Values are mean ± SE.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4418729&req=5

pone.0125252.g004: Time course of above steady-state insulin secretion rate, SR(t), during 90-min IVGTT in our ZFR group (n = 7, closed circles) and ZLR group (n = 7, open circles).Values are mean ± SE.
Mentions: Quantification of β-cell function was achieved by the interpretation of C-peptide data by the minimal model of C-peptide secretion (CPMM). CPMM provided a good fit to C-peptide data, as judged from the average weighted residuals (over all fourteen rats, Fig 3) which showed no systematic deviation from zero and were within the range [-1, +1]. This behavior is consistent with the hypothesis that the measurement error was a random variable normally distributed, around zero. Estimates of main CPMM parameters and steady-state indexes in individual rats are given in Table 2 for ZLRs and ZFRs. Precision is given in parentheses. The individual estimates of the other model parameters have been reported in S1 Table. A significant difference in mean estimates of Φ1 (116%, Fig 2B), Φ2 (418%, Fig 2C) and Φss (927%) was detected in the ZFR group, compared with the ZLR group, indicating an overall enhanced responsiveness of β-cell secretion to glucose stimulus. Mean steady-state secretion rate, SRss (min-1·pmol/L), was significantly higher in the ZFR group (498±85) compared to the ZLR group (47.8±9.6). Mean above steady-state secretion rate, SR(t), showed a significant increase in our ZFR group, between 0 and 25 min (Fig 4). Thus, total insulin secretion rate TSR(t) (TSR(t) = SR(t) + SRSS, see Eq A8 in the Appendix 1), was significantly higher in the ZFR group throughout the entire IVGTT. Integration of TSR(t), over 90 min yielded a significant 761% increase in total insulin secretion per unit of distribution volume, TIS, in the ZFR group (Fig 2D).

Bottom Line: 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, Ф(1), second-phase, Ф(2), and steady-state, Ф(ss), 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy.

ABSTRACT
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-9 week-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, Ф(1), second-phase, Ф(2), and steady-state, Ф(ss), 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.

No MeSH data available.


Related in: MedlinePlus