scholarly journals Evaluation of quantitative models of the effect of insulin on lipolysis and glucose disposal

2008 ◽  
Vol 295 (4) ◽  
pp. R1089-R1096 ◽  
Author(s):  
Vipul Periwal ◽  
Carson C. Chow ◽  
Richard N. Bergman ◽  
Madia Ricks ◽  
Gloria L. Vega ◽  
...  
Keyword(s):  
Model Comparison ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Model Complexity ◽  
Glucose Disposal ◽  
Intravenous Glucose ◽  
Bayesian Model Comparison ◽  
Plasma Ffa ◽  
Second Category ◽  
Glucose Dynamics

The effects of insulin on the suppression of lipolysis are neither fully understood nor quantified. We examined a variety of mathematical models analogous to the minimal model of glucose disposal (MMG) to quantify the combined influence of insulin on lipolysis and glucose disposal during an insulin-modified frequently sampled intravenous glucose tolerance test. The tested models, which include two previously published ones, consisted of separate compartments for plasma free fatty acids (FFA), glucose, and insulin. They differed in the number of compartments and in the action of insulin to suppress lipolysis that decreased the plasma FFA level. In one category of models, a single insulin compartment acted on both glucose and FFA simultaneously. In a second category, there were two insulin compartments, each acting on FFA and glucose independently. For each of these two categories, we tested 11 variations of how insulin suppressed lipolysis. We also tested a model with an additional glucose compartment that acted on FFA. These 23 models were fit to the plasma FFA and glucose concentrations of 102 subjects individually. Using Bayesian model comparison methods, we selected the model that best balanced fit and minimized model complexity. In the best model, insulin suppressed lipolysis via a Hill function through a remote compartment that acted on both glucose and FFA simultaneously, and glucose dynamics obeyed the classic MMG.

Glucose effectiveness is the major determinant of intravenous glucose tolerance in the rat

1999 ◽  
Vol 276 (4) ◽  
pp. E739-E746 ◽  
Author(s):  
M. Dawn McArthur ◽  
Dan You ◽  
Kim Klapstein ◽  
Diane T. Finegood
Keyword(s):  
Glucose Tolerance ◽  
Bolus Injection ◽  
Insulin Response ◽  
Tolerance Test ◽  
Physiological Effect ◽  
Intravenous Glucose Tolerance Test ◽  
Glucose Disposal ◽  
Disappearance Rate ◽  
Intravenous Glucose ◽  
Intravenous Glucose Tolerance

To determine the importance of insulin for glucose disposal during an intravenous glucose tolerance test in rats, experiments were performed in four cohorts of conscious unrestrained rats fasted overnight. In cohorts 1- 3, a bolus of tracer ([3-3H]glucose, 50 μCi) was given alone, with glucose (0.3 g/kg) to induce an endogenous insulin response (∼1,100 pmol/l), or with exogenous insulin to give physiological (1,700 pmol/l) or supraphysiological (12,000 pmol/l) plasma levels. Raising plasma insulin within the physiological range had no effect ( P > 0.05), but supraphysiological levels induced hypoglycemia (7.3 ± 0.2 to 3.6 ± 0.2 mmol/l) and increased [3H]glucose disappearance rate ( P < 0.001). In cohort 4, a primed, continuous tracer infusion was started 120 min before saline or glucose bolus injection. [3H]glucose levels fell 15–20%, and the disappearance rate rose 36% ( P < 0.05) after glucose injection. These results indicate that in fasted rats a tracer bolus injection protocol is not sufficiently sensitive to measure the physiological effect of insulin released in response to a bolus of glucose because this effect of insulin is small. Glucose itself is the predominant mediator of glucose disposal after a bolus of glucose in the fasted rat.

scholarly journals Measurement of selective effect of insulin on glucose disposal from labeled glucose oral test minimal model

2005 ◽  
Vol 289 (5) ◽  
pp. E909-E914 ◽  
Author(s):  
Chiara Dalla Man ◽  
Andrea Caumo ◽  
Rita Basu ◽  
Robert Rizza ◽  
Gianna Toffolo ◽  
...  
Keyword(s):  
Minimal Model ◽  
Glucose Production ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Intravenous Glucose ◽  
Selective Effect ◽  
Clamp Technique ◽  
Model Independent

The oral glucose minimal model (OMM) measures insulin sensitivity (SI) and the glucose rate of appearance (Ra) of ingested glucose in the presence of physiological changes of insulin and glucose concentrations. However, SI of OMM measures the overall effect of insulin on glucose utilization and glucose production. In this study we show that, by adding a tracer to the oral dose, e.g., of a meal, and by using the labeled version of OMM, OMM* to interpret the data, one can measure the selective effect of insulin on glucose disposal, [Formula: see text]. Eighty-eight individuals underwent both a triple-tracer meal with the tracer-to-tracee clamp technique, providing a model-independent reference of the Ra of ingested glucose ([Formula: see text]) and an insulin-modified labeled intravenous glucose tolerance test (IVGTT*). We show that OMM* provides not only a reliable means of tracing the Ra of ingested glucose (Ra meal) but also accurately measures [Formula: see text]. We do so by comparing OMM* Ra meal with the model-independent [Formula: see text] provided by the tracer-to-tracee clamp technique, while OMM* [Formula: see text] is compared with both [Formula: see text], obtained by using as known input [Formula: see text], and with [Formula: see text] measured during IVGTT*.

The hot IVGTT two-compartment minimal model: an improved version

2003 ◽  
Vol 284 (2) ◽  
pp. E317-E321 ◽  
Author(s):  
Gianna Toffolo ◽  
Claudio Cobelli
Keyword(s):  
Minimal Model ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Glucose Disposal ◽  
Parameter Estimates ◽  
Model Parameters ◽  
Single Individual ◽  
Intravenous Glucose ◽  
Proportional Effect ◽  
Effect Of Glucose

The two-compartment minimal model (2CMM) interpretation of a labeled intravenous glucose tolerance test (IVGTT) is a powerful tool to assess glucose metabolism in a single individual. It has been reported that a derived 2CMM parameter describing the proportional effect of glucose on insulin-independent glucose disposal can take physiologically unplausible negative values. In addition, precision of 2CMM parameter estimates is sometimes not satisfactory. Here we resolve the above issues by presenting an improved version of 2CMM that relies on a new assumption on the constant component Rd0 of insulin-independent glucose disposal. Here Rd0 is not fixed to 1 mg · kg−1 · min−1but instead is expressed as a fraction of steady-state glucose disposal. The new 2CMM is identified on the same stable labeled IVGTT data base on which the original 2CMM was formulated. A more reliable insulin-independent glucose disposal portrait is obtained while that of insulin action remains unchanged. The new 2CMM also improves the precision with which model parameters and metabolic indexes are estimated.

scholarly journals Partitioning glucose distribution/transport, disposal, and endogenous production during IVGTT

2002 ◽  
Vol 282 (5) ◽  
pp. E992-E1007 ◽  
Author(s):  
Roman Hovorka ◽  
Fariba Shojaee-Moradie ◽  
Paul V. Carroll ◽  
Ludovic J. Chassin ◽  
Ian J. Gowrie ◽  
...  
Keyword(s):  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Glucose Disposal ◽  
Intravenous Glucose ◽  
Endogenous Production ◽  
Lower Glucose ◽  
Tracer Dilution ◽  
Kinetics Of ◽  
Male Subjects ◽  
Stimulation Of

We have separated the effect of insulin on glucose distribution/transport, glucose disposal, and endogenous production (EGP) during an intravenous glucose tolerance test (IVGTT) by use of a dual-tracer dilution methodology. Six healthy lean male subjects (age 33 ± 3 yr, body mass index 22.7 ± 0.6 kg/m2) underwent a 4-h IVGTT (0.3 g/kg glucose enriched with 3–6% d-[U-13C]glucose and 5–10% 3- O-methyl-d-glucose) preceded by a 2-h investigation under basal conditions (5 mg/kg ofd-[U-13C]glucose and 8 mg/kg of 3- O-methyl-d-glucose). A new model described the kinetics of the two glucose tracers and native glucose with the use of a two-compartment structure for glucose and a one-compartment structure for insulin effects. Insulin sensitivities of distribution/transport, disposal, and EGP were similar (11.5 ± 3.8 vs. 10.4 ± 3.9 vs. 11.1 ± 2.7 × 10−2ml · kg−1 · min−1 per mU/l; P = nonsignificant, ANOVA). When expressed in terms of ability to lower glucose concentration, stimulation of disposal and stimulation of distribution/transport accounted each independently for 25 and 30%, respectively, of the overall effect. Suppression of EGP was more effective ( P < 0.01, ANOVA) and accounted for 50% of the overall effect. EGP was suppressed by 70% (52–82%) (95% confidence interval relative to basal) within 60 min of the IVGTT; glucose distribution/transport was least responsive to insulin and was maximally activated by 62% (34–96%) above basal at 80 min compared with maximum 279% (116–565%) activation of glucose disposal at 20 min. The deactivation of glucose distribution/transport was slower than that of glucose disposal and EGP ( P < 0.02) with half-times of 207 (84–510), 12 (7–22), and 29 (16–54) min, respectively. The minimal-model insulin sensitivity was tightly correlated with and linearly related to sensitivity of EGP ( r = 0.96, P < 0.005) and correlated positively but nonsignificantly with distribution/transport sensitivity ( r = 0.73, P = 0.10) and disposal sensitivity ( r = 0.55, P = 0.26). We conclude that, in healthy subjects during an IVGTT, the two peripheral insulin effects account jointly for approximately one-half of the overall insulin-stimulated glucose lowering, each effect contributing equally. Suppression of EGP matches the effect in the periphery.

Relationship of insulin sensitivity to aerobic capacity in Standardbred mares and geldings

2005 ◽  
Vol 2 (3) ◽  
pp. 185-193 ◽  
Author(s):  
SE Pratt ◽  
RJ Geor ◽  
LJ McCutcheon
Keyword(s):  
Insulin Sensitivity ◽  
Aerobic Capacity ◽  
Serum Insulin ◽  
Insulin Response ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Glucose Disposal ◽  
Intravenous Glucose ◽  
Condition Score ◽  
Relationship Of

AbstractThe objective of this study was to determine the relationship between insulin sensitivity and aerobic capacity and serum adipocytokine (leptin, adiponectin) concentrations in 14 mature, unconditioned Standardbred horses (eight mares, six geldings). Each horse underwent a euglycaemic–hyperinsulinaemic clamp (EHC) and a frequently sampled intravenous glucose tolerance test (FSIGT) for assessment of insulin sensitivity. Aerobic capacity was determined by measurement of the peak rate of oxygen uptake (V˙O2peak) during an incremental exercise test (IET). Serum leptin and adiponectin concentrations were measured in baseline samples obtained before tests of insulin sensitivity. Mean body weight, condition score, V˙O2peak and run time during the IET did not differ between the sex groups. However, minimal model analysis of the FSIGT showed that insulin sensitivity (SI, ×10−4 l mU−1 min−1) was higher (P = 0.002) in geldings (4.21±0.78) than in mares (2.43±0.95), while the acute insulin response to glucose (AIRg) and glucose utilization independent of insulin (SG) were significantly higher in mares. Similarly, glucose uptake (M) per unit of serum insulin (I) during the EHC (M/I ratio) tended (P = 0.08) to be higher in geldings than in mares (×10−2 mg kg−1 min−1 per μU ml−1: 2.41±0.64 vs. 1.80±0.51). There was no significant relationship between V˙O2peak and measures of insulin sensitivity. Stepwise multiple linear regression modelling determined that sex (65%) and leptin concentrations (13.7%) accounted for 78.7% of the variance in SI, while 46% of the variance in M/I could be attributed to sex. It was concluded that aerobic capacity is not an important determinant of insulin-mediated glucose disposal in mature, untrained Standardbred horses. Further studies are needed to examine the influence of gender on insulin sensitivity in horses.

Estimation of insulin sensitivity and glucose clearance from minimal model: new insights from labeled IVGTT

1986 ◽  
Vol 250 (5) ◽  
pp. E591-E598 ◽  
Author(s):  
C. Cobelli ◽  
G. Pacini ◽  
G. Toffolo ◽  
L. Sacca
Keyword(s):  
Insulin Sensitivity ◽  
Minimal Model ◽  
Glucose Production ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Glucose Disposal ◽  
Model Estimate ◽  
Intravenous Glucose ◽  
Glucose Inhibition ◽  
Glucose Clearance

The "minimal model" of glucose disappearance provides noninvasive estimates of insulin sensitivity and glucose effectiveness from an intravenous glucose tolerance test (IVGTT). However, this model does not allow the separation of glucose production from utilization. To overcome this limitation, labeled glucose was injected along with cold glucose in six normal dogs, and both cold and labeled glucose time courses were monitored along with insulin concentration. A revised minimal model was fitted to tracer data to obtain new measures of insulin sensitivity (SI* = 6.41 +/- 0.91 10(-4) min-1 X microU-1 X ml-1) and fractional glucose clearance (SG* = 0.0092 +/- 0.0009 min-1). SG* was compared with a direct measure obtained by a hepatic arterial-venous difference technique, which yielded a value of 0.0097 +/- 0.0002, virtually identical to SG*, thereby validating the model estimate. When the original minimal model was identified from cold data, we obtained S1 = 4.52 +/- 1.39 and SG = 0.042 +/- 0.009. SI* and SG* were different from SI and SG, respectively. In particular SG overestimates fractional glucose clearance by approximately five times. The revised minimal model yields glucose disposal parameters SI* and SG* that are not affected by the confounding effect of insulin and glucose inhibition of glucose production. Limitations inherent in cold IVGTT and original minimal model are overcome by labeled IVGTT and the revised minimal model, while test simplicity remains.

Distinct but nonadditive effects of epinephrine and cortisol on determinants of glucose tolerance in dogs

1991 ◽  
Vol 260 (1) ◽  
pp. E148-E153
Author(s):  
I. K. Martin ◽  
M. J. Christopher ◽  
F. P. Alford ◽  
J. D. Best
Keyword(s):  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Glucose Disposal ◽  
Inhibitory Effects ◽  
Intravenous Glucose ◽  
Nonadditive Effects ◽  
Dominant Influence ◽  
Infusion Period

Effects of physiological increments of epinephrine (Epi) and cortisol (F) on glucose metabolism were assessed in dogs just before and during an intravenous glucose tolerance test performed in the last 3 h of an acute (short F + Epi, 4 h F and 3.5 h Epi) or prolonged (long F + Epi, 75 h F and Epi) infusion period. Comparison of the F + Epi effects with those of F and Epi alone enabled us to describe interactions between these hormones. The increase in plasma glucose after long F + Epi [from control (saline, Sal) of 5.2 +/- 0.1 to 5.8 +/- 0.1 mmol/l; n = 8; P less than 0.01] was not greater than the sum of the glucose increments after long F and long Epi individually. Long Epi and long F both reduced glucose tolerance (KGlc) significantly, but the decline during long F + Epi (from Sal 3.6 +/- 0.7 to 2.9 +/- 0.5%/min; P greater than 0.1) was less than during either individual infusion. Minimal model analysis showed that F attenuated the inhibitory effects of long Epi on glucose-mediated glucose disposal (SGlc), so that it was not reduced from 3.8 +/- 0.8 (Sal) during long F + Epi compared with the fall to 1.3 +/- 0.7 x 10(-2) min-1 (n = 6; P less than 0.05) during long Epi alone. F had the dominant influence on insulin sensitivity (SI) during infusion of F + Epi. The reduction of SI from 8.4 +/- 1.1 (Sal) to 6.6 +/- 1.2 (short F + Epi) and 5.1 +/- 1.1 x 10(-4) min-1 per mU/l (long F + Epi; P less than 0.05) paralleled that seen with F alone but contrasted with the acute reduction of SI during short Epi (4.8 +/- 1.5; P less than 0.02 vs. Sal) and its restoration to control values of 9.0 +/- 2.1 x 10(-4) min-1 per mU/l during long Epi. We conclude that Epi and F have distinct but nonadditive effects on determinants of glucose tolerance.

APPLICATION DE LA DOUBLE ÉPREUVE D'HYPERGLYCÉMIE INTRAVEINEUSE À L'ÉTUDE DU DIABÈTE

1960 ◽  
Vol XXXIII (II) ◽  
pp. 157-167
Author(s):  
T. Rodari ◽  
G. Specchia
Keyword(s):  
Glucose Tolerance ◽  
Pancreatic Islet ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Intravenous Glucose ◽  
Intravenous Glucose Tolerance ◽  
Glucose Assimilation

ABSTRACT The double intravenous glucose tolerance test does not modify the assimilation coefficient in normal and thin diabetic subjects. On the contrary, in fat diabetic subjects the second coefficient of assimilation increases significantly, but not the first one. From these researches it is evident that the valuation of glucose assimilation by double venous hyperglycaemic test indicates the functional behaviour of the pancreas in different diabetic states. The interpretation of this behaviour of pancreatic islet response to the double venous hyperglycaemic test is discussed.

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