scholarly journals Comparison of insulin sensitivity between healthy neonatal foals and horses using minimal model analysis

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262584
Author(s):  
Hannah M. Kinsella ◽  
Laura D. Hostnik ◽  
Hailey A. Snyder ◽  
Sarah E. Mazur ◽  
Ahmed M. Kamr ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Minimal Model ◽  
Cell Function ◽  
Insulin Response ◽  
Model Analysis ◽  
Intravenous Glucose Tolerance Test ◽  
Model Assessment ◽  
Intravenous Glucose ◽  
Glucose Ratio

The equine neonate is considered to have impaired glucose tolerance due to delayed maturation of the pancreatic endocrine system. Few studies have investigated insulin sensitivity in newborn foals using dynamic testing methods. The objective of this study was to assess insulin sensitivity by comparing the insulin-modified frequently sampled intravenous glucose tolerance test (I-FSIGTT) between neonatal foals and adult horses. This study was performed on healthy neonatal foals (n = 12), 24 to 60 hours of age, and horses (n = 8), 3 to 14 years of age using dextrose (300 mg/kg IV) and insulin (0.02 IU/kg IV). Insulin sensitivity (SI), acute insulin response to glucose (AIRg), glucose effectiveness (Sg), and disposition index (DI) were calculated using minimal model analysis. Proxy measurements were calculated using fasting insulin and glucose concentrations. Nonparametric statistical methods were used for analysis and reported as median and interquartile range (IQR). SI was significantly higher in foals (18.3 L·min-1· μIU-1 [13.4–28.4]) compared to horses (0.9 L·min-1· μIU-1 [0.5–1.1]); (p < 0.0001). DI was higher in foals (12 × 103 [8 × 103−14 × 103]) compared to horses (4 × 102 [2 × 102−7 × 102]); (p < 0.0001). AIRg and Sg were not different between foals and horses. The modified insulin to glucose ratio (MIRG) was lower in foals (1.72 μIUinsulin2/10·L·mgglucose [1.43–2.68]) compared to horses (3.91 μIU insulin2/10·L·mgglucose [2.57–7.89]); (p = 0.009). The homeostasis model assessment of beta cell function (HOMA-BC%) was higher in horses (78.4% [43–116]) compared to foals (23.2% [17.8–42.2]); (p = 0.0096). Our results suggest that healthy neonatal foals are insulin sensitive in the first days of life, which contradicts current literature regarding the equine neonate. Newborn foals may be more insulin sensitive immediately after birth as an evolutionary adaptation to conserve energy during the transition to extrauterine life.

scholarly journals Overestimation of minimal model glucose effectiveness in presence of insulin response is due to undermodeling

1998 ◽  
Vol 275 (6) ◽  
pp. E1031-E1036 ◽  
Author(s):  
Claudio Cobelli ◽  
Francesca Bettini ◽  
Andrea Caumo ◽  
Michael J. Quon
Keyword(s):  
Glucose Tolerance ◽  
Minimal Model ◽  
Insulin Response ◽  
Model Analysis ◽  
Published Data ◽  
Glucose Kinetics ◽  
Model Estimate ◽  
Intravenous Glucose ◽  
Glucose Effectiveness ◽  
Model Independent

Glucose effectiveness is an important determinant of glucose tolerance that can be derived from minimal model analysis of an intravenous glucose tolerance test (IVGTT). However, recent evidence suggests that glucose effectiveness is overestimated by minimal model analysis. Here we compare a new model-independent estimate of glucose effectiveness with the minimal model estimate by reanalyzing published data in which insulin-dependent diabetic subjects were each given IVGTTs under two conditions (Quon, M. J., C. Cochran, S. I. Taylor, and R. C. Eastman. Diabetes 43: 890–896, 1994). In one case, a basal insulin level was maintained (BI-IVGTT). In the second case, a dynamic insulin response was recreated (DI-IVGTT). Our results show that minimal model glucose effectiveness is very similar to the model-independent measurement during a BI-IVGTT but is three times higher during a DI-IVGTT. To investigate the causes of minimal model overestimation in the presence of a dynamic insulin response, Monte Carlo simulation studies on a two-compartment model of glucose kinetics with various insulin response patterns were performed. Results suggest that minimal model overestimation is due to single-compartment representation of glucose kinetics that results in a critical oversimplification in the presence of increasingly dynamic insulin secretion patterns.

Modified protocols improve insulin sensitivity estimation using the minimal model

1987 ◽  
Vol 253 (6) ◽  
pp. E595-E602 ◽  
Author(s):  
Y. J. Yang ◽  
J. H. Youn ◽  
R. N. Bergman
Keyword(s):  
Standard Deviation ◽  
Insulin Sensitivity ◽  
Minimal Model ◽  
Insulin Response ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Improve Insulin Sensitivity ◽  
Intravenous Glucose ◽  
Sensitivity Estimation ◽  
Model Technique

We attempted to improve the precision of the estimation of insulin sensitivity (S1) from the minimal model technique by modifying insulin dynamics during a frequently sampled intravenous glucose tolerance test (FSIGT). Tolbutamide and somatostatin (SRIF) were used to change the insulin dynamics without directly affecting insulin sensitivity. Injection of tolbutamide (100 mg) at t = 20 min provoked an immediate secondary peak in insulin response, resulting in a greater integrated incremental insulin than the standard FSIGT. SRIF, injected at t = -1 min, delayed insulin secretion in proportion to the dose without any change in magnitude. Computer simulation was used to assess the precision of S1 estimation. Insulin dynamics from both standard and modified protocols were adjusted in magnitude, with the shape unchanged and analyzed to determine the effect of the magnitude of insulin response. Fractional standard deviation was reduced from 73% with the standard insulin profile to 23% with tolbutamide and 18% with the highest dose of SRIF. In addition, the fractional standard deviation of S1 estimates decreased exponentially with increasing magnitude of insulin response. Modified FSIGTs require a smaller insulin response than the standard protocol to achieve the same precision.

The effect of age and exercise training on insulin sensitivity, fat and muscle tissue cytokine profiles and body composition of old and young Standardbred mares

2012 ◽  
Vol 8 (3-4) ◽  
pp. 173-187 ◽  
Author(s):  
N.R. Liburt ◽  
M.N. Fugaro ◽  
K. Malinowski ◽  
E.K. Wunderlich ◽  
J.L. Zambito ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Repeated Measures ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Insulin Response ◽  
Intravenous Glucose Tolerance Test ◽  
Necrosis Factor Alpha ◽  
Intravenous Glucose ◽  
Cytokine Profiles

This study tested the hypothesis that old and young mares exhibit different endocrine responses to a frequently sampled intravenous glucose tolerance test (FSIGT) and different cytokine profiles in blood, adipose and muscle tissues. It was also hypothesised that exercise training alters endocrine and tissue cytokine profiles. Pilot data from 15 mixed background horses indicated tissue differences in cytokine profiles. For the main study, six old (22.0±0.7 years) and six young (7.3±0.6 years; mean±SE) unfit Standardbred mares were tested pre- and post-training. Exercise training occurred three days/week for 15 weeks at ~60% maximum heart rate. Plasma insulin and glucose concentrations were measured via radioimmunoassay and enzyme-electrode interface, respectively. Samples of blood, middle gluteal muscle (RM), and subcutaneous adipose tissue from the neck (NF) were collected pre- and post-training for mRNA quantification. Minimal model analysis of FSIGT, repeated measures ANOVA and Pearson Product Moment were used to analyse data. The null hypothesis was rejected when P≤l0.10. Post-training, old and young mares improved insulin sensitivity (SI) (P=0.08, P=0.01, respectively) and disposition index (P=0.04, P<0.001, respectively), but acute insulin response to glucose increased in young mares only (P=0.02). Old mares exhibited lower (P=0.06) average relative quantity (RQ) of tumour necrosis factor-alpha in NF compared to RM. Old mares showed greater RQ of interleukin-6 (IL-6) in NF compared to young (P=0.08). A negative correlation was observed between SI and IL-6 in NF post-training (P=0.07, R=-0.54), and a positive correlation occurred between SI and monocyte chemotactic protein-1 in NF post-training (P=0.08, R=0.53). Exercise training improved pancreatic beta cell function and insulin sensitivity in old and young horses. Cytokines associated with glucose metabolism may have varied roles in different tissues.

Reappraisal of the intravenous glucose tolerance index for a simple assessment of insulin sensitivity in mice

2009 ◽  
Vol 296 (5) ◽  
pp. R1316-R1324 ◽  
Author(s):  
Giovanni Pacini ◽  
Maria Ahrén ◽  
Bo Ahrén
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Minimal Model ◽  
Simple Procedure ◽  
Intravenous Glucose Tolerance Test ◽  
Tolerance Index ◽  
Common Procedure ◽  
Intravenous Glucose ◽  
Intravenous Glucose Tolerance ◽  
Large Numbers

Mice are increasingly used in studies where measuring insulin sensitivity (IS) is a common procedure. The glucose clamp is labor intensive, cannot be used in large numbers of animals, cannot be repeated in the same mouse, and has been questioned as a valid tool for IS in mice; thus, the minimal model with 50-min intravenous glucose tolerance test (IVGTT) data was adapted for studies in mice. However, specific software and particular ability was needed. The aim of this study was to establish a simple procedure for evaluating IS during IVGTT in mice (CSI). IVGTTs ( n = 520) were performed in NMRI and C57BL/6J mice (20–25g). After glucose injection (1 g/kg), seven samples were collected for 50 min for glucose and insulin measurements, analyzed with a minimal model that provided the validated reference IS (SI). By using the regression CSI = α1 + α2 × KG/AUCD, where KG is intravenous glucose tolerance index and AUCd is the dynamic area under the curve, IS was calculated in 134 control animals randomly selected (regression CSI vs. SI: r = 0.66, P < 0.0001) and yielded α1 = 1.93 and α2 = 0.24. KG is the slope of log (glucose5-20) and AUCD is the mean dynamic area under insulin curve in the IVGTT. By keeping fixed α1 and α2, CSI was validated in 143 control mice (4.7 ± 0.2 min·μU−1·ml−1, virtually identical to SI: 4.7 ± 0.3, r = 0.89, P < 0.0001); and in 123 mice in different conditions: transgenic, addition of neuropeptides, incretins, and insulin (CSI: 6.0 ± 0.4 vs. SI: 6.1 ± 0.4, r = 0.94, P < 0.0001). In the other 120 animals, CSI revealed its ability to segregate different categories, as does SI. This easily usable formula for calculating CSI overcomes many experimental obstacles and may be a simple alternative to more complex procedures when large numbers of mice or repeated experiments in the same animals are required.

scholarly journals When MINMOD Artifactually Interprets Strong Insulin Secretion as Weak Insulin Action

2021 ◽  
Vol 12 ◽  
Author(s):  
Joon Ha ◽  
Ranganath Muniyappa ◽  
Arthur S. Sherman ◽  
Michael J. Quon
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Minimal Model ◽  
Insulin Response ◽  
Reference Method ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Intravenous Glucose ◽  
Model Studies ◽  
Increased Risk

We address a problem with the Bergman-Cobelli Minimal Model, which has been used for 40 years to estimate SI during an intravenous glucose tolerance test (IVGTT). During the IVGTT blood glucose and insulin concentrations are measured in response to an acute intravenous glucose load. Insulin secretion is often assessed by the area under the insulin curve during the first few minutes (Acute Insulin Response, AIR). The issue addressed here is that we have found in simulated IVGTTs, representing certain contexts, Minimal Model estimates of SI are inversely related to AIR, resulting in artifactually lower SI. This may apply to Minimal Model studies reporting lower SI in Blacks than in Whites, a putative explanation for increased risk of T2D in Blacks. The hyperinsulinemic euglycemic clamp (HIEC), the reference method for assessing insulin sensitivity, by contrast generally does not show differences in insulin sensitivity between these groups. The reason for this difficulty is that glucose rises rapidly at the start of the IVGTT and reaches levels independent of SI, whereas insulin during this time is determined by AIR. The minimal model in effect interprets this combination as low insulin sensitivity even when actual insulin sensitivity is unchanged. This happens in particular when high AIR results from increased number of readily releasable insulin granules, which may occur in Blacks. We conclude that caution should be taken when comparing estimates of SI between Blacks and Whites.

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