Exercise-induced changes in insulin action are associated with ACE gene polymorphisms in older adults

2002 ◽  
Vol 11 (2) ◽  
pp. 73-80 ◽  
Author(s):  
Donald R. Dengel ◽  
Michael D. Brown ◽  
Robert E. Ferrell ◽  
Thomas H. Reynolds ◽  
Mark A. Supiano
Keyword(s):  
Insulin Action ◽  
Insulin Response ◽  
Exercise Program ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Before And After ◽  
Ace Genotype ◽  
Exercise Induced

We evaluated the association between insulin resistance and the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism in a group of older hypertensive subjects (63 ± 1 yr, n = 35) before and after a 6-mo aerobic exercise program (AEX). Insulin sensitivity index (SI), assessed by the frequently sampled intravenous glucose tolerance test, was significantly ( P = 0.0001) increased following AEX. In addition, there was a significant ( P = 0.001) interaction between AEX and ACE genotype. SI increased significantly ( P < 0.05) more in those with the II (2.5 ± 0.8 μU × 10−4 · min−1 · ml−1) ACE genotype compared with both the DD and ID (0.7 ± 0.1 and 0.7 ± 0.2 μU × 10−4 · min−1 · ml−1, respectively) ACE genotypes. Similarly, there was a significant ( P = 0.036) decrease in the acute insulin response to glucose (AIRG) and a significant ( P = 0.05) interaction between AEX and ACE genotype. AIRG decreased significantly ( P < 0.05) more in those with the II (−17.6 ± 5.6 mU/ml) ACE genotype compared with both the DD and ID (−1.4 ± 6.2 and −3.6 ± 2.5 mU/ml) ACE genotypes. In conclusion, we demonstrated that those older hypertensives with the ACE II genotype have the greatest improvement in insulin action following AEX.

scholarly journals Physical Fitness, Activity, and Insulin Dynamics in Early Pubertal Children

2009 ◽  
Vol 21 (1) ◽  
pp. 63-76 ◽  
Author(s):  
Krista Casazza ◽  
Barbara A. Gower ◽  
Amanda L. Willig ◽  
Gary R. Hunter ◽  
José R. Fernández
Keyword(s):  
Physical Activity ◽  
Ethnic Differences ◽  
Insulin Response ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Independent Effect ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
American Children ◽  
Racial Ethnic

The objectives of this study were to identify the independent effect of physical activity and fitness on insulin dynamics in a cohort of European-, African-, and Hispanic-American children (n = 215) age 7–12 years and to determine if racial/ethnic differences in insulin dynamics could be statistically explained by racial/ethnic differences in physical activity or fitness. An intravenous glucose tolerance test and minimal modeling were used to derive the insulin sensitivity index (SI) and acute insulin response to glucose (AIRg). Fitness was assessed as VO2-170 and physical activity by accelerometer. Multiple regression models were tested for contributions of fitness and physical activity to SI and AIRg. Fitness was a stronger predictor of SI and AIRg than physical activity regardless of ethnicity; racial/ethnic differences in insulin dynamics were not accounted for by differences in fitness and/or physical activity.

scholarly journals First-phase insulin response (FPIR) to intravenous glucose tolerance test (IVGTT), insulin sensitivity and long-term follow-up in ?- transfusion-dependent thalassemia (TDT) normoglycemic patients with reduced insulin secretion to oral glucose tolerance t

2021 ◽  
Vol 13 (1) ◽  
pp. e2021021
Author(s):  
Vincenzo De Sanctis
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Insulin Response ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Intravenous Glucose

Summary. Objective: To  study the function of the endocrine pancreas in transfusion-dependent ?-thalassemia (?-TDT) patients with normal oral glucose tolerance test (OGTT) and hypoinsulinemia. Patients and methods: Seven ?-TDT patients  (mean age 22.4 ± 4.2 years) with normal glucose tolerance test (NGT) and poor insulin response (hypoinsulinemia) to OGTT,  not associated with ?-cell autoimmunity, were referred for a second opinion to an Italian Centre, part of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A). In this pilot study,  the first-phase insulin response (FPIR), expressed as the sum of 1 and  3 minutes insulin, of ?-TDT patients to intravenous glucose tolerance test (IVGTT), was tested. Moreover, the long-term natural history was followed prospectively using an annual OGTT, with the aim of detecting any abnormality of glucose metabolism. Results: The FPIR value  was between the 1st and 3rd percentile in two patients and between the 3rd and 10th percentile in  five. After 43 ± 26 months (range 11 - 80 months) of follow-up, 2 patients developed impaired glucose tolerance (IGT), 3 both IGT and impaired fasting glucose (IFG) and two overt diabetes mellitus (DM). Interestingly, the patients who developed DM had, at baseline the lowest value of insulinogenic index (IGI, 0.08 and 0.25), defined as the ratio of the increment of plasma insulin to plasma glucose during the first 30 minutes after OGTT. Moreover, a significant correlation was found between the IGI at baseline and at follow-up in the patients who developed IGT with or without IFG (R= 0.927; P: 0.023). A significant reduction of Matsuda insulin sensitivity index (ISIM) and Insulin Secretion-Sensitivity Index-2 (ISSI-2) was documented in the study cohort at diagnosis of IFG, IGT and DM. There was a significant inverse correlation between ISSI-2 and area under the curve of plasma glucose (AUC-PG). Conclusions: These data demonstrated, for the first time, a progressive deterioration in glucose homeostasis in ?-TDT subjects with NGT and hypoinsulinemia.  Thus, we consider that variations of insulin sensitivity could possibly have an impact on glucose tolerance in adult patients with TDT. Further investigations should focus on factors that might positively influence insulin sensitivity, including nutrition, drugs and physical activity.  

Hyperinsulinemic Compensation For Insulin Resistance Occurs Independent Of Elevated Glycemia In Male Dogs

Endocrinology ◽  
2021 ◽  
Author(s):  
Marilyn Ader ◽  
Richard N Bergman
Keyword(s):  
Insulin Resistance ◽  
Subcutaneous Fat ◽  
Insulin Response ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Intravenous Glucose ◽  
Primary Element ◽  
Subcutaneous Adiposity ◽  
Hyperinsulinemic Compensation

Abstract Insulin resistance (IR) engenders a compensatory increase in plasma insulin. Inadequate compensation is a primary element in the pathogenesis of Type 2 diabetes. The signal which heralds developing IR and initiates hyperinsulinemic compensation is not known. It has often been assumed to be increased glucose. We tested this assumption by determining whether development of fasting and/or glucose-stimulated hyperinsulinemia with diet-induced insulin resistance occurs because of concomitant elevation of glycemia. Male dogs (n=58) were fed a hypercaloric, fat-supplemented diet for 6 wks. Dogs underwent MRI to quantify total and regional (visceral, subcutaneous) adiposity as well as euglycemic hyperinsulinemic clamps. A subset of animals also underwent an insulin-modified intravenous glucose tolerance test (IVGTT) to assess insulin sensitivity, acute insulin response (AIRg), and glucose effectiveness. Fat feeding caused modest weight gain, increased visceral and subcutaneous fat, and IR at both peripheral and hepatic levels. Hyperinsulinemic compensation was observed in fasting levels as well as increased AIRg. However, we observed absolutely no increase in carefully measured fasting, evening (6-8 pm) or nocturnal glycemia (2-4 am). IR and hyperinsulinemia occurred despite no elevation in 24-hour glucose. Compensatory development of hyperinsulinemia during diet-induced insulin resistance occurs without elevated fasting or 24-hour glycemia. These data refute the idea that glucose itself is a requisite signal for β-cell upregulation. Alternative feedback mechanisms need to be identified.

Decline in insulin action with age in endurance-trained humans

2002 ◽  
Vol 93 (6) ◽  
pp. 2105-2111 ◽  
Author(s):  
Christopher M. Clevenger ◽  
Pamela Parker Jones ◽  
Hirofumi Tanaka ◽  
Douglas R. Seals ◽  
Christopher A. DeSouza
Keyword(s):  
Endurance Exercise ◽  
Insulin Action ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Whole Body ◽  
Intravenous Glucose ◽  
Trained Subjects ◽  
Age Related ◽  
Similar Body

We tested the hypothesis that regular endurance exercise prevents the age-related decline in insulin action typically observed in healthy, sedentary adults. An index of whole body insulin sensitivity (ISI), obtained from minimal model analysis of insulin and glucose concentrations during a frequently sampled intravenous glucose tolerance test, was determined in 126 healthy adults: 25 young [27 ± 1 (SE) yr; 13 men/12 women] and 43 older (59 ± 1 yr; 20/13) sedentary and 25 young (29 ± 1 yr; 12/13) and 33 older (60 ± 1 yr; 20/13) endurance trained. ISI values were lower in the older vs. young adults in both sedentary (−53%; 3.9 ± 0.3 vs. 7.0 ± 0.7 ×10−4 · min−1 · μU−1 · ml−1; P < 0.01) and endurance-trained (−36%; 7.9 ± 0.6 vs. 12.4 ± 1.0 ×10−4min−1 · μU−1 · ml−1; P < 0.01) groups, but the value was 72–102% higher in the trained subjects at either age ( P < 0.01). In subgroup analysis of sedentary and endurance-trained adults with similar body fat levels ( n = 62), the age-related reduction in ISI persisted only in the endurance-trained subjects (12.9 ± 1.9 vs. 8.7 ± 1.2 ×10−4 · min−1 · μU−1 · ml−1; P < 0.01). The results of the present study suggest that habitual endurance exercise does not prevent the age-associated decline insulin action. Moreover, the age-related reduction in ISI in endurance-trained adults appears to be independent of adiposity.

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.

Assessment of Insulin Sensitivity in Man: A Comparison of Minimal Model- and Euglycaemic Clamp-Derived Measures in Health and Heart Failure

1994 ◽  
Vol 86 (3) ◽  
pp. 317-322 ◽  
Author(s):  
Jonathan W. Swan ◽  
Christopher Walton ◽  
Ian F. Godsland
Keyword(s):  
Heart Failure ◽  
Insulin Sensitivity ◽  
Minimal Model ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
High Dose ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Intravenous Glucose Tolerance

1. Simplified protocols for the measurement of insulin resistance will facilitate studies of this potentially important variable. 2. Using the euglycaemic clamp as the reference technique, we have assessed the validity of the insulin sensitivity index (inversely related to insulin resistance) obtained using a high-dose (500 mg/kg), unmodified intravenous glucose tolerance test with a 16 point sampling schedule and analysis using the minimal model of glucose disappearance. The two methods were compared in 10 clinically normal subjects and five patients with severe heart failure secondary to coronary heart disease. 3. The insulin sensitivity index of the minimal model was compared with four clamp-derived measures. Correlation coefficients of 0.72–0.92 (P < 0.01−P < 0.001) were obtained between the two methods over a wide range of insulin sensitivity [model values 1.03–14.63 min−1/(pmol/l) × 10−5]. Patients with heart failure had the lowest measures of insulin sensitivity. 4. The high-dose, unmodified intravenous glucose tolerance test with minimal model analysis is a straightforward and economical clinical procedure and provides a valid measure of insulin sensitivity, in health and disease.

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.

GLUCOSE METABOLISM IN TRAUMATIC BRAIN INJURY

1974 ◽  
Vol 77 (1) ◽  
pp. 103-110 ◽  
Author(s):  
V. Keymolen-Jardini ◽  
E. Mouawad ◽  
P. Claeys-De Clercq ◽  
E. Van Laer ◽  
S. Levin ◽  
...  
Keyword(s):  
Amino Nitrogen ◽  
Insulin Response ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Plasma Growth Hormone ◽  
Intravenous Glucose ◽  
Brain Contusion ◽  
Male Patients ◽  
Low K ◽  
Normal Controls

ABSTRACT The present study was designed to evaluate some key metabolic parameters in patients suffering from a traumatic brain contusion with coma. This evaluation was carried out before and during an intravenous glucose tolerance test (iv – GTT) in 6 male patients paired with normal controls Four patients presented a fasting hyperglycaemia and a low K rate of glucose disappearance but the basal level of insulin was normal or high and the insulin response to the glucose load was not significantly impaired. The basal level of plasma growth hormone (HGH) was usually normal but it increased paradoxically during the iv – GTT; 2 patients had a striking hyper-response. Plasma cortisol levels were always elevated. On the other hand no gross or systematic anomaly in the regulation of plasma free fatty acids, acetoacetate and amino nitrogen was detected. The paradoxical HGH response was the only finding which could be specifically attributed to the central neural lesions.

scholarly journals Top Single Nucleotide Polymorphisms Affecting Carbohydrate Metabolism in Metabolic Syndrome: From the LIPGENE Study

2014 ◽  
Vol 99 (2) ◽  
pp. E384-E389 ◽  
Author(s):  
Javier Delgado-Lista ◽  
Pablo Perez-Martinez ◽  
Juan Solivera ◽  
Antonio Garcia-Rios ◽  
A. I. Perez-Caballero ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Single Nucleotide Polymorphisms ◽  
Carbohydrate Metabolism ◽  
Insulin Response ◽  
Intravenous Glucose Tolerance Test ◽  
Sensitivity Index ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Intravenous Glucose

Rationale: Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk. Objectives: Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS. Methods: A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study. Findings: From 382 initial gene-phenotype associations between SNPs and any phenotypic variables, 61 (16% of the preselected variables) remained significant after bootstrapping. Top SNPs affecting glucose metabolism variables were as follows: fasting glucose, rs26125 (PPARGC1B); fasting insulin, rs4759277 (LRP1); C-peptide, rs4759277 (LRP1); homeostasis assessment of insulin resistance, rs4759277 (LRP1); quantitative insulin sensitivity check index, rs184003 (AGER); sensitivity index, rs7301876 (ABCC9), acute insulin response to glucose, rs290481 (TCF7L2); and disposition index, rs12691 (CEBPA). Conclusions: We describe here the top SNPs linked to phenotypic features in carbohydrate metabolism among approximately 1000 candidate gene variations in fasting and postprandial samples of 450 patients with MetS from the LIPGENE study.

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