1,720,968 research outputs found
Contribution of 3-hydroxyisobutyrate to the measurement of 3-hydroxybutyrate in human plasma: comparison of enzymatic and gas-liquid chromatography-mass spectrometry assays in normal and in diabetic subjects.
No full textEpinephrine's ketogenic effect in humans is mediated principally by lipolysis.
No full textTo quantify epinephrine's effects on acetoacetate and beta-hydroxybutyrate kinetics, we infused subjects with 0.3 and 2.5 micrograms/min epinephrine, either alone or with a concomitant somatostatin infusion with insulin, glucagon, and growth hormone replaced at postabsorptive levels (islet clamp). Additional subjects received no epinephrine but sequential infusions of heparin plus 10% Intralipid at rates of 0.5 and 3.0 ml/min. Both epinephrine and Intralipid increased ketone body appearance (unaffected by islet clamp), augmented the interconversion rates between ketone bodies and, during the 2.5 micrograms/min infusion, caused a marked increase in beta-hydroxybutyrate appearance. The fraction of plasma free fatty acid (FFA) flux appearing as plasma ketones increased from 6 to 7% in the basal state to 11% at the high-epinephrine infusion. This fraction was also unaffected by the islet clamp and was not different from values obtained at similar Intralipid plus heparin-induced elevations in plasma FFA levels. We conclude that epinephrine's ketogenic effect in humans is primarily the result of its lipolytic effect, is accompanied by a significantly increased rate of ketone body interconversion, is manifest largely as an increase in plasma beta-hydroxybutyrate appearance at high plasma epinephrine values, and is not limited by portal insulin at post-absorptive levels.</jats:p
Glucose production, gluconeogenesis and insulin sensitivity in children and adolescents: an evaluation of their reproducibility
No full textThe prevalence of overweight and obese children has doubled, and the incidence of type 2 diabetes in children (0-19 y) has increased 4-fold during the past several decades. As a result we can anticipate an increased number of metabolic studies in children. There are few data on measures of glucose metabolism in normal children, and virtually none relating to their reproducibility. The aims of this study were 1) to provide new data on energy expenditure and glucose, lipid, and protein metabolism in nonobese, healthy children and adolescents; 2) to evaluate their reproducibility; and 3) on the basis of these data, to perform power calculations for metabolic studies. Eight nonobese subjects (8-16 y) were studied on two occasions, preceded by 7 d of a diet with identical energy content and macronutrient distribution. Gluconeogenesis, measured by deuterium oxide, accounted for 50% of glucose production. Insulin sensitivity, measured by the labeled minimal model, averaged 4.9 x 10(-4) mL(mU x min)(-1). Glucose appearance rate was significantly higher (p < 0.01) in the children than in the adolescents. Furthermore, we demonstrated that for energy intake and expenditure, plasma concentrations of glucose and C-peptide, and rates of appearance of glucose and leucine, a 10% difference can be detected in fewer than five subjects with a power of 80% and a type I error of 5%. Insulin concentration, gluconeogenesis, insulin secretory indices, insulin sensitivity, and glucose effectiveness were more variable, but with the above power a difference of 25% could be detected in 7-11 subjects using a paired study design
Glucose production during an IVGTT by deconvolution: validation with the tracer-to-tracee clamp technique
No full textRecently, a new method, based on a two-compartment minimal model and deconvolution [A. Caumo and C. Cobelli. Am. J. Physiol 264 (Endocrinol. Metab. 37): E829-E841, 1993; P. Vicini, G. Sparacino, A. Caumo, and C. Cobelli. Comput. Meth. Prog. Biomed. 52: 147-156, 1997], has been proposed to estimate endogenous glucose production (EGP) from labeled intravenous glucose tolerance test (IVGTT) data. Our aim here is to compare this EGP profile with that independently obtained with the reference method, based on the tracer-to-tracee ratio (TTR) clamp. An insulin-modified (0.03 U/kg body wt infused over 5 min) [6,6-2H2]glucose-labeled IVGTT (0.33 g/kg of glucose) was performed in 10 normal subjects. A second tracer ([U-13C]glucose) was also infused during the test in a variable fashion to clamp endogenous glucose TTR. The TTR clamp was quite successful. As a result, the EGP profile, reconstructed from [U-13C]glucose data with the models of Steele and Radziuk, were almost superimposable. The deconvolution-obtained EGP profile, calculated from [6,6-2H2]glucose data, showed remarkable agreement with that obtained from the TTR clamp. Some differences between the two profiles were noted in the estimated basal EGP and in the initial modalities of EGP inhibition. A high interindividual variability was also observed with both methods in the resumption of EGP to baseline; variability was high in both the timing and the extent of resumption. In conclusion, the use of the two-compartment minimal model of the IVGTT and deconvolution allows the estimation of a profile of EGP that is in very good agreement with that independently obtained with a TTR clamp
Effects of cyclosporine on insulin secretion and insulin sensitivity in dogs with intrasplenic islet autotransplants
No full textAbstract: Concern about cyclosporine causing adverse effects on glucose metabolism is based mainly on in vitro studies and in vivo data in rodents. However, data on large mammals and humans are much more controversial. Because the drug is used as therapy accompanying pancreatic or isolated islet transplantations, studies in large animals are needed to assess whether cyclosporine inhibits beta-cell function and causes glucose intolerance. To address these issues, we examined intravenous glucose tolerance, islet beta-cell function, and insulin sensitivity in a group of adult mongrel dogs with intrasplenic islet autografts, with and without cyclosporine treatment. Similar fasting plasma glucose and insulin values were found before and after pancreatectomy and islet transplantation. After intravenous glucose, plasma glucose values decreased more slowly in dogs that had undergone transplantation, but not additional adverse effect as a result of cyclosporine was observed. During euglycemic clamp studies, performed at both physiologic and pharmacologic insulin concentrations, the drug had no effect on the total amount of metabolized glucose, and glucose production was unaffected by cyclosporine treatment. Thus intramuscular cyclosporine therapy does not seem to inhibit insulin secretion from heterotopic islets or to affect peripheral and hepatic insulin sensitivity in dogs with intrasplenic islet autografts
Effects of dietary macronutrient content on glucose metabolism in children
No full textEffects of carbohydrate, fat, and fructose intake on substrate and hormone concentrations, glucose production, gluconeogenesis, and insulin sensitivity were determined in healthy, nonobese prepubertal children (n = 12) and adolescents (n = 24) using a cross-over design. In one group (12 prepubertal children and 12 adolescents), subjects were studied after 7 d of isocaloric, isonitrogenous diets providing either 60% carbohydrate and 25% fat [high carbohydrate (H(CHO))/low fat (L(F))] or 30% carbohydrate and 55% fat [low carbohydrate (L(CHO))/high fat (H(F))], and in a second group (12 adolescents) H(CHO)/L(F) diets containing either 40% or 10% fructose was used. All subjects adapted to changes in carbohydrate and fat intakes primarily by appropriately adjusting their substrate oxidation rates to match the intakes, with only minor changes in parameters of glucose metabolism. Changing from a L(CHO)/H(F) to H(CHO)/L(F) diet resulted in increased insulin sensitivity (stable labeled iv glucose tolerance test) in adolescents [from 3.2 +/- 0.7 x 10(-4) to 5.0 +/- 1.4 x 10(-4) (min(-1))/( micro U.ml(-1)) (mean +/- SE)] but not in prepubertal children [9.4 +/- 2.5 x 10(-4) to 9.9 +/- 1.5 x 10(-4) (min(-1))/( micro U.ml(-1))], whereas beta-cell sensitivity was unaffected in both groups. Insulin sensitivity was higher in prepubertal children than in adolescents (P < 0.05). The dietary fructose content did not affect any measured parameter. We conclude that in the short term, dramatic changes in fat and carbohydrate intakes (regardless of fructose content) did not adversely affect glucose and lipid metabolism in healthy nonobese children. In the adolescents, the high carbohydrate diet resulted in increased insulin sensitivity, thus facilitating insulin-mediated glucose uptake
Short-term high dietary fructose intake had no effects on insulin sensitivity and secretion or glucose and lipid metabolism in healthy, obese adolescents
No full textThere is virtually no information on the metabolic impact of dietary fructose intake in adolescents despite their high fructose consumption, particularly via sweetened beverages.
AIM:
To determine the short-term metabolic effects of dietary fructose intake in obese adolescents.
METHODS:
Six volunteers (3 M/3 F; 15.2 +/- 0.5 yr; 35 +/- 2 kg/m2; 39 +/- 2% body fat) were studied twice following 7 d of isocaloric, isonitrogenous high carbohydrate (60% CHO; 25% fat) diets with fructose accounting for 6% and 24% of total energy intake, respectively (random order). Insulin sensitivity and secretion were analyzed by the stable labeled intravenous glucose tolerance test and glucose and lipid kinetics using GCMS.
RESULTS:
A fourfold increase in dietary fructose intake did not affect insulin sensitivity or secretion, glucose kinetics, lipolysis or glucose, insulin, C-peptide, triglycerides, HDL- and LDL-cholesterol concentrations.
CONCLUSIONS:
In the short term, when energy intake is constant, dietary fructose per se is not a contributor to insulin resistance and hypersecretion in obese adolescents
Role of GH in regulating nocturnal rates of lipolysis and plasma mevalonate levels in normal and diabetic humans.
No full textUndermodeling affects minimal model indexes: insights from a two-compartment model
No full textIF 3,6
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