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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 plasma glucose (G(t), panel A) insulin (I(t), panel B) and C-peptide (CP(t), panel C) concentrations 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.g001: Time course of plasma glucose (G(t), panel A) insulin (I(t), panel B) and C-peptide (CP(t), panel C) concentrations during 90-min IVGTT in our ZFR group (n = 7, closed circles) and ZLR group (n = 7, open circles).Values are mean ± SE.

Mentions: Compared to the age-matched ZLR group, the ZFR group was characterized by having, on average, significantly higher body weight (BW), systolic (SAP), diastolic (DAP) and mean (MAP) aortic pressure, and fasting plasma concentration of glucose, insulin and C-peptide (Table 1). The time courses of mean (±SE) glucose, G(t), insulin I(t) and C-peptide, CP(t), plasma levels, throughout the entire IVGTT, are represented in Fig 1A, 1B and 1C, respectively. A significant increase was observed in the ZFR group, compared with the ZLR group, throughout the entire IVGTT for CP(t), between 1 and 70 min for I(t), and between 8 and 15 min for G(t).


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 plasma glucose (G(t), panel A) insulin (I(t), panel B) and C-peptide (CP(t), panel C) concentrations 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.g001: Time course of plasma glucose (G(t), panel A) insulin (I(t), panel B) and C-peptide (CP(t), panel C) concentrations during 90-min IVGTT in our ZFR group (n = 7, closed circles) and ZLR group (n = 7, open circles).Values are mean ± SE.
Mentions: Compared to the age-matched ZLR group, the ZFR group was characterized by having, on average, significantly higher body weight (BW), systolic (SAP), diastolic (DAP) and mean (MAP) aortic pressure, and fasting plasma concentration of glucose, insulin and C-peptide (Table 1). The time courses of mean (±SE) glucose, G(t), insulin I(t) and C-peptide, CP(t), plasma levels, throughout the entire IVGTT, are represented in Fig 1A, 1B and 1C, respectively. A significant increase was observed in the ZFR group, compared with the ZLR group, throughout the entire IVGTT for CP(t), between 1 and 70 min for I(t), and between 8 and 15 min for G(t).

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