Glucose turnover in humans in the basal state and after intravenous glucose: a comparison of two models

Overkamp, D.; Gautier, J.-F.; Renn, W.; Pickert, A.; Scheen, André; Schmülling, R.-M.; Eggstein, M.; Lefèbvre, Pierre

doi:10.1152/ajpendo.1997.273.2.e284

Cited by 11 publications

(8 citation statements)

References 17 publications

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“…To avoid the potential impact on insulin action/glucose metabolism of the rise in estrogen and testosterone levels associated with the onset of puberty, an iv glucose tolerance test was performed, according to the established method of Overkamp et al (1997), sequentially, i.e. 3–5 times, on each baboon offspring at 6–12 month intervals between the postnatal ages of 1 and 3¼ years of age, i.e.…”

Section: Methodsmentioning

confidence: 99%

Estrogen deprivation in primate pregnancy leads to insulin resistance in offspring

Maniu

Aberdeen

Lynch

et al. 2016

Journal of Endocrinology

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This study tested the hypothesis that estrogen programs mechanisms within the primate fetus that promote insulin sensitivity and glucose homeostasis in offspring. Glucose tolerance tests were performed longitudinally in prepubertal offspring of baboons untreated or treated on days 100 to 165/175 of gestation (term is 184 days) with the aromatase inhibitor letrozole which decreased fetal estradiol levels by 95%. Basal plasma insulin levels were over 2-fold greater in offspring delivered to letrozole-treated than untreated animals. Moreover, the peak 1 min, average of the 1, 3 and 5 min, and area under the curve blood glucose and plasma insulin levels after an iv bolus of glucose were greater (P<0.05 and P<0.01, respectively) in offspring deprived of estrogen in utero than in untreated animals and partially or completely restored in letrozole plus estradiol-treated baboons. The value for the homeostasis model assessment of insulin resistance was 2.5-fold greater (P<0.02) and quantitative insulin sensitivity check index lower (P<0.01) in offspring of letrozole-treated versus untreated animals and returned to almost normal in letrozole plus estradiol-treated animals. The exaggerated rise in glucose and insulin levels after glucose challenge in baboon offspring deprived of estrogen in utero indicates that pancreatic beta cells had the capacity to secrete insulin, but that peripheral glucose uptake and/or metabolism were impaired, indicative of insulin resistance and glucose intolerance. We propose that estrogen normally programs mechanisms in utero within the developing primate fetus that lead to insulin sensitivity, normal glucose tolerance and the capacity to metabolize glucose after birth.

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Section: Methodsmentioning

confidence: 99%

Estrogen deprivation in primate pregnancy leads to insulin resistance in offspring

Maniu

Aberdeen

Lynch

et al. 2016

Journal of Endocrinology

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“…An iv glucose tolerance test was performed essentially as described previously [1], according to the established method of Overkamp et al [18], sequentially (1–4 times) on each baboon offspring at 6–12 month intervals after onset of puberty between the ages of 4¼ (females)/5 (males) years and 8 years of age. Intravenous glucose tolerance test results in individual animals did not change between 4¼–8 years of age and thus the data obtained from the individual iv GTT performed was averaged to yield a single value for each animal.…”

Section: Methodsmentioning

confidence: 99%

Insulin resistance elicited in postpubertal primate offspring deprived of estrogen in utero

et al. 2016

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We recently demonstrated that offspring delivered to baboons deprived of estrogen during the second half of gestation exhibited insulin resistance prior to onset of puberty. Because gonadal hormones have a profound effect on insulin action and secretion in adults, we determined whether insulin resistance is retained after initiation of gonadal secretion of testosterone and estradiol. Glucose tolerance tests were performed in postpubertal baboon offspring of untreated and letrozole-treated animals (serum estradiol reduced >95 %). Basal fasting levels of insulin (P < 0.05) and peak 1 min and 1 + 3 + 5 min levels of glucose after glucose tolerance tests challenge (P < 0.03) were greater in offspring delivered to letrozole-treated, estrogen-deprived baboons than untreated animals. Moreover, the value for the HOMA-IR, an accepted index of insulin resistance, was 2-fold greater (P < 0.05) in offspring delivered to baboons treated with letrozole than in untreated animals. Collectively these results support the proposal that estrogen normally has an important role in programming mechanisms in utero within the developing fetus that lead to insulin sensitivity after birth.

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“…Recently, the deconvolution approach has been validated with the tracer-to-tracee ratio (TTR) clamp technique, which uses a model-independent method to estimate EGP under the constraint that glucose specific activity is held constant throughout the IVGTT (45). Although the use of a deconvolution technique minimizes the role of the model used to represent the glucose system response (35), neither one of these techniques provides a mechanistic description of liver glucose production, nor of its regulation by glucose and insulin. Moreover, deconvolution can be computationally demanding and requires nontrivial choices of a regularization parameter and virtual grid (44).…”

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confidence: 99%

Integrated model of hepatic and peripheral glucose regulation for estimation of endogenous glucose production during the hot IVGTT

Krudys¹,

Dodds²,

Nissen³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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, and a new parameter describing the sensitivity of EGP to the inhibitory effect of insulin (IC50 ϭ 0.0195 Ϯ 0.0046 min Ϫ1 ). The model additionally provided an estimate of the time course of EGP showing almost immediate inhibition, followed by a secondary inhibitory effect caused by infusion of insulin, and a large overshoot as EGP returns to its basal value. Our estimates show very good agreement with those obtained via deconvolution and the model-independent TTR clamp technique. These results suggest that the new integrated model can serve as a simple one-step approach to obtain metabolic indexes while also providing a parametric description of EGP.hot minimal model; intravenous glucose tolerance test; mathematical modeling; insulin sensitivity AS THE BODY'S MAIN SOURCE of endogenous glucose production (EGP), the liver plays a crucial role in maintaining normal glucose homeostasis. In response to a glucose challenge, insulin is secreted, and the resultant hyperglycemia and hyperinsulinemia conspire to suppress hepatic glucose production and stimulate glucose uptake in splanchnic and peripheral tissues. During the course of disease progression, however, the liver may become resistant to the suppressive effects of glucose and insulin on glucose production. The resulting excess production acts to maintain the chronic hyperglycemic state observed in type 2 diabetics. It is therefore of great interest to accurately assess the dynamic regulation of EGP in response to a glucose perturbation.The dynamic picture emerging from glucose and insulin's time course after an intravenous glucose tolerance test (IVGTT) has allowed remarkable and unique insights into the pathophysiology of glucose homeostasis (8), especially when coupled with the parametric information available when the data are analyzed with the minimal model of glucose disappearance (9). Over the years, the metabolic indexes of glucose effectiveness (3) and insulin sensitivity (38) estimated via the minimal model have been subjected to experimental validation against equivalent experimental designs, and insulin sensitivity has been found to be an informative predictor of cardiovascular risk (27) and to be strongly related to genetic factors (10). New protocols that modify the standard IVGTT to facilitate minimal-model parameter estimation have also been proposed, such as an infusion of insulin (22) or tolbutamide administration (7) and variations thereof (39,40).Among other modifications of the standard IVGTT, the addition of a tracer of glucose to the glucose bolus was proposed as a way to dissect the respective roles of liver and periphery in glucose dynamics (14). This augmented information allowed clarification of the impact of some of the underlying assumptions of the original minimal model, in particular the single-compartment approximation for glucose distribution (15), which does not allow a plausible estimate of EGP in the early portion of the test, and seems to impact the estimate of glucose effectiveness more severely than it does insulin sensitiv...

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Glucose turnover in humans in the basal state and after intravenous glucose: a comparison of two models

Cited by 11 publications

References 17 publications

Estrogen deprivation in primate pregnancy leads to insulin resistance in offspring

Estrogen deprivation in primate pregnancy leads to insulin resistance in offspring

Insulin resistance elicited in postpubertal primate offspring deprived of estrogen in utero

Integrated model of hepatic and peripheral glucose regulation for estimation of endogenous glucose production during the hot IVGTT

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