Glucose Tolerance Test In Humans Research Articles

Acylated- and unacylated ghrelin during an oral glucose tolerance test in humans at risk for type 2 diabetes mellitus

Background/ObjectivesThe orexigenic peptide hormone ghrelin has been implicated in the pathophysiology of obesity and type 2 diabetes mellitus through its effects on nutrient homeostasis. Ghrelin is subject to a unique post-translational acyl modification regulating its biochemical activity.Subjects/MethodsIn this study we aimed to investigate the relation of acylated (AcG) as well as unacylated ghrelin (UnG) with body weight and insulin resistance in the fasting (n = 545) and post-oral glucose tolerance test (oGTT) state (n = 245) in a metabolically well characterized cohort covering a broad range of BMI (17.95 kg/m²–76.25 kg/m²).ResultsFasting AcG (median 94.2 pg/ml) and UnG (median 175.3 pg/ml) were negatively and the AcG/UnG ratio was positively correlated with BMI (all p < 0.0001). Insulin sensitivity (ISI) correlated positively with AcG (p = 0.0014) and UnG (p = 0.0004) but not with the AcG/UnG ratio. In a multivariate analysis, including ISI and BMI, only BMI, but not ISI was independently associated with AcG and UnG concentrations. Significant changes of AcG and UnG concentrations were detectable after oGTT stimulation, with slight decreases after 30 min and increases after 90–120 min. Subject stratification into BMI-divergent groups revealed more pronounced AcG increases in the two groups with BMI < 40 kg/m².ConclusionOur data demonstrate lower concentrations for both AcG and UnG with increasing BMI as well as an increased proportion of the biologically active, acylated form of ghrelin giving point to pharmacologic intervention in ghrelin acylation and/or increase in UnG for treatment of obesity despite decreased absolute AcG levels.

Circulating Concentrations of Insulin Resistance-Associated Hepatokines, Selenoprotein P and Leukocyte Cell-Derived Chemotaxin 2, during an Oral Glucose Tolerance Test in Humans.

A hepatokine is a collective term for liver-derived secretory factors whose previously-unrecognized functions have been recently elucidated. We have rediscovered selenoprotein P (SeP) and leukocyte cell-derived chemotaxin 2 (LECT2) as hepatokines that are involved in the development of insulin resistance and hyperglycemia. The aim of this study was to determine whether and, if so, how oral glucose loading alters the two hepatokines in humans. We measured concentrations of serum SeP and plasma LECT2 during 75 g oral glucose tolerance test (OGTT) (n = 20) in people with various degrees of glucose tolerance. In OGTT, concentrations of both serum SeP and plasma LECT2 decreased at 120 min compared with the baseline values, irrespective of the severity of glucose intolerance. Decrement of serum SeP during OGTT showed no correlations to the clinical parameters associated with insulin resistance or insulin secretion. In multiple stepwise regression analyses, plasma cortisol was selected as the variable to explain the changes in plasma concentrations of LECT2. The current data reveal the acute inhibitory actions of oral intake of glucose on circulating SeP and LECT2 in humans, irrespective of the severity of glucose intolerance. This study suggests that circulating SeP is regulated by the unknown clinical factors other than insulin and glucose during OGTT.

Functional Variant in the GCKR Gene Affects Lactate Levels Differentially in the Fasting State and During Hyperglycemia

The rs780094 single nucleotide polymorphism (SNP; C/T) of glucokinase regulatory protein gene (GCKR) is a regulatory genetic variant that has been associated with lactate levels in the fasting state. However, the association of this locus with lactate during hyperglycemia, and the mechanisms underlying these associations remain unknown. We investigated the association of rs780094 with lactate levels in a frequently sampled oral glucose tolerance test in humans and evaluated the effect of increasing GCKR expression on lactate production in liver cells. The C allele of rs780094 was associated with lower lactate levels in fasting but increased lactate level during hyperglycemia independently of insulin levels. Increased expression of GKRP induced higher lactate level in HepG2 cells and in human primary hepatocytes (HPH) upon glucose stimulation by increasing the amount of GCK. Glucagon induced the expression of GCKR in HepG2 and HPH cells. Our results suggest that the association of rs780094 with lactate levels may involve differential GCKR expression between the carriers of the C and T alleles.

Minimal modeling of glucose-insulin interactions in the intravenous glucose tolerance test

The minimal model of glucose and insulin plasma levels is commonly used to analyze the results of glucose tolerance tests in humans. In this paper, a mathematical model for describing the glucose infusion rate was introduced. The minimal model was used to study a few sets of published data including healthy humans and type 2 diabetes. The glucose-insulin system as a dynamic integrated physiological system and generated the real optimized model parameters from the experimental data using the modified minimal model. The averaged R 2 value between measured and calculated plasma concentrations wais 0.977, which indicates excellent agreement.

The effect of post-exercise caffeine and chlorogenic acid supplementation on blood glucose disposal and insulin sensitivity

Background Caffeine and chlorogenic acid are two compounds in green coffee beans that alter blood glucose disposal and insulin sensitivity. Caffeine has been shown to decrease glucose disposal and insulin sensitivity when taken 60 minutes prior to an oral glucose tolerance test in humans, whereas chlorogenic acid has been shown to increase glucose disposal and insulin sensitivity in humans. The purpose of this study was to investigate the effect of ingesting caffeine with dextrose or chlorogenic acid with dextrose immediately after an exhaustive bout of cycling on blood glucose and insulin disposal when compared to ingesting dextrose alone. Methods

Modified minimal model for effect of physical exercise on insulin sensitivity and glucose effectiveness in type 2 diabetes and healthy human

The Bergman's minimal model of glucose and insulin plasma levels is commonly used to analyse the results of glucose tolerance tests in humans. In this paper, we present the modified minimal model with plasma insulin compartment under the assumption that if the plasma glucose compartment drops below the basal glucose levels, the rate of insulin entering the plasma glucose compartment is zero. Insulin is cleared from the plasma insulin compartment at a rate proportional to the amount of insulin in the plasma insulin compartment. The modified minimal model was used to study the effect of physical exercise via parameters of a mathematical model to qualitative the magnitude of changes in insulin sensitivity (S(I)) and glucose effectiveness (S(G)) in response to exercise in type 2 diabetes and healthy human. The short-term effects of physical exercise in type 2 diabetes did not improve S(G), but markedly improved the low S(I) values found in type 2 diabetes, indicating that the effects of exercise on S(I) are quantitatively important in the interpretation of training-related S(I) changes and may even be therapeutically useful in type 2 diabetes patients. Physical exercise is indicated either to prevent or delay the onset of type 2 diabetes or to assure a good control of type 2 diabetes by increasing insulin sensitivity.

Prehepaticβ-Cell Secretion During the Intravenous Glucose Tolerance Test in Humans: Application of a Combined Model of Insulin and C-Peptide Kinetics*

A previously introduced method by which prehepatic beta-cell secretion is calculated in vivo from plasma measurements of insulin and C-peptide was applied to data derived from iv glucose tolerance tests performed in normal women. Prehepatic secretory rates calculated using the combined model appeared biphasic in nature after glucose injection. Basal insulin secretion was 63.9 +/- 9.8 pmol/min. The duration of first phase was approximately 5 min, with secretion reaching a peak of 2033 +/- 342 pmol/min. The first phase was followed by a significant refractory period in which the secretory rate fell below basal values. The magnitude of second phase secretion was small relative to first phase secretion and appeared pulsatile in nature. Total integrated insulin secretion was 22.2 +/- 2.7 nmol, of which first phase accounted for 32%, and second phase accounted for the remaining 68%. Total incremental integrated secretion was 10.6 +/- 1.4 nmol, accounting for approximately half of the total insulin secretion. Proportions of first and second phase secretion changed to 66.5% and 33.5%, respectively, with incremental data. This study shows that the combined model of insulin and C-peptide is capable of estimating prehepatic insulin secretion from the iv glucose tolerance test and may provide a useful tool to measure secretion in vivo under various pathological conditions.