The effect of age and exercise training on insulin sensitivity, fat and muscle tissue cytokine profiles and body composition of old and young Standardbred mares

2012 ◽  
Vol 8 (3-4) ◽  
pp. 173-187 ◽  
Author(s):  
N.R. Liburt ◽  
M.N. Fugaro ◽  
K. Malinowski ◽  
E.K. Wunderlich ◽  
J.L. Zambito ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Repeated Measures ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Insulin Response ◽  
Intravenous Glucose Tolerance Test ◽  
Necrosis Factor Alpha ◽  
Intravenous Glucose ◽  
Cytokine Profiles

This study tested the hypothesis that old and young mares exhibit different endocrine responses to a frequently sampled intravenous glucose tolerance test (FSIGT) and different cytokine profiles in blood, adipose and muscle tissues. It was also hypothesised that exercise training alters endocrine and tissue cytokine profiles. Pilot data from 15 mixed background horses indicated tissue differences in cytokine profiles. For the main study, six old (22.0±0.7 years) and six young (7.3±0.6 years; mean±SE) unfit Standardbred mares were tested pre- and post-training. Exercise training occurred three days/week for 15 weeks at ~60% maximum heart rate. Plasma insulin and glucose concentrations were measured via radioimmunoassay and enzyme-electrode interface, respectively. Samples of blood, middle gluteal muscle (RM), and subcutaneous adipose tissue from the neck (NF) were collected pre- and post-training for mRNA quantification. Minimal model analysis of FSIGT, repeated measures ANOVA and Pearson Product Moment were used to analyse data. The null hypothesis was rejected when P≤l0.10. Post-training, old and young mares improved insulin sensitivity (SI) (P=0.08, P=0.01, respectively) and disposition index (P=0.04, P<0.001, respectively), but acute insulin response to glucose increased in young mares only (P=0.02). Old mares exhibited lower (P=0.06) average relative quantity (RQ) of tumour necrosis factor-alpha in NF compared to RM. Old mares showed greater RQ of interleukin-6 (IL-6) in NF compared to young (P=0.08). A negative correlation was observed between SI and IL-6 in NF post-training (P=0.07, R=-0.54), and a positive correlation occurred between SI and monocyte chemotactic protein-1 in NF post-training (P=0.08, R=0.53). Exercise training improved pancreatic beta cell function and insulin sensitivity in old and young horses. Cytokines associated with glucose metabolism may have varied roles in different tissues.

scholarly journals Comparison of insulin sensitivity between healthy neonatal foals and horses using minimal model analysis

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262584
Author(s):  
Hannah M. Kinsella ◽  
Laura D. Hostnik ◽  
Hailey A. Snyder ◽  
Sarah E. Mazur ◽  
Ahmed M. Kamr ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Minimal Model ◽  
Cell Function ◽  
Insulin Response ◽  
Model Analysis ◽  
Intravenous Glucose Tolerance Test ◽  
Model Assessment ◽  
Intravenous Glucose ◽  
Glucose Ratio

The equine neonate is considered to have impaired glucose tolerance due to delayed maturation of the pancreatic endocrine system. Few studies have investigated insulin sensitivity in newborn foals using dynamic testing methods. The objective of this study was to assess insulin sensitivity by comparing the insulin-modified frequently sampled intravenous glucose tolerance test (I-FSIGTT) between neonatal foals and adult horses. This study was performed on healthy neonatal foals (n = 12), 24 to 60 hours of age, and horses (n = 8), 3 to 14 years of age using dextrose (300 mg/kg IV) and insulin (0.02 IU/kg IV). Insulin sensitivity (SI), acute insulin response to glucose (AIRg), glucose effectiveness (Sg), and disposition index (DI) were calculated using minimal model analysis. Proxy measurements were calculated using fasting insulin and glucose concentrations. Nonparametric statistical methods were used for analysis and reported as median and interquartile range (IQR). SI was significantly higher in foals (18.3 L·min-1· μIU-1 [13.4–28.4]) compared to horses (0.9 L·min-1· μIU-1 [0.5–1.1]); (p < 0.0001). DI was higher in foals (12 × 103 [8 × 103−14 × 103]) compared to horses (4 × 102 [2 × 102−7 × 102]); (p < 0.0001). AIRg and Sg were not different between foals and horses. The modified insulin to glucose ratio (MIRG) was lower in foals (1.72 μIUinsulin2/10·L·mgglucose [1.43–2.68]) compared to horses (3.91 μIU insulin2/10·L·mgglucose [2.57–7.89]); (p = 0.009). The homeostasis model assessment of beta cell function (HOMA-BC%) was higher in horses (78.4% [43–116]) compared to foals (23.2% [17.8–42.2]); (p = 0.0096). Our results suggest that healthy neonatal foals are insulin sensitive in the first days of life, which contradicts current literature regarding the equine neonate. Newborn foals may be more insulin sensitive immediately after birth as an evolutionary adaptation to conserve energy during the transition to extrauterine life.

scholarly journals The effects of aerobic, resistance, and combination training on insulin sensitivity and secretion in overweight adults from STRRIDE AT/RT: a randomized trial

2015 ◽  
Vol 118 (12) ◽  
pp. 1474-1482 ◽  
Author(s):  
Hiba AbouAssi ◽  
Cris A. Slentz ◽  
Catherine R. Mikus ◽  
Charles J. Tanner ◽  
Lori A. Bateman ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Resistance Training ◽  
Exercise Training ◽  
Aerobic Training ◽  
Cell Function ◽  
Intravenous Glucose Tolerance Test ◽  
Disposition Index ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Glucose Effectiveness

Most health organizations recommend a combination of aerobic training (AT) and resistance training (RT), yet few studies have compared their acute (within 24 h of the last exercise bout) and sustained (after 14 days of no exercise training) effects alone and in combination on glucose metabolism. The present study (Studies Targeting Risk Reduction Interventions through Defined Exercise-Aerobic Training and/or Resistance Training) compared the effects of AT, RT, and the combination (AT/RT) on insulin action at both acute and sustained phases. Subjects ( N = 196) were 18-70 yr old (mean age = 50 yr), overweight (mean body mass index = 30 kg/m2), sedentary with moderate dyslipidemia, and were randomized into one of three 8-mo exercise groups: 1) RT: 3 days/wk, 8 exercises, 3 sets/exercise, 8–12 repetitions/set; 2) AT: equivalent to ∼19.2 km/wk (12 miles/wk) at 75% peak O2 consumption; 3) AT/RT: the combination of AT and RT. One hundred forty-four subjects completed the intervention. Eighty-eight subjects completed all pre- and postintervention testing visits. Insulin sensitivity, glucose effectiveness, and disposition index were measured via a frequently sampled intravenous glucose tolerance test with subsequent minimal model analyses. AT/RT resulted in greater improvements in insulin sensitivity, β-cell function (disposition index), and glucose effectiveness than either AT or RT alone (all P < 0.05). Approximately 52% of the improvement in insulin sensitivity by AT/RT was retained 14 days after the last exercise training bout. Neither AT or RT led to acute or chronic improvement in sensitivity index. In summary, only AT/RT (which required twice as much time as either alone) led to significant acute and sustained benefits in insulin sensitivity.

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.

scholarly journals Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation

2009 ◽  
Vol 106 (4) ◽  
pp. 1079-1085 ◽  
Author(s):  
Sudip Bajpeyi ◽  
Charles J. Tanner ◽  
Cris A. Slentz ◽  
Brian D. Duscha ◽  
Jennifer S. McCartney ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Insulin Action ◽  
High Volume ◽  
Intravenous Glucose Tolerance Test ◽  
Moderate Intensity ◽  
Intravenous Glucose ◽  
Obese Subjects ◽  
Vigorous Intensity ◽  
Low Volume

The purpose of this study was to determine whether exercise prescriptions differing in volume or intensity also differ in their ability to retain insulin sensitivity during an ensuing period of training cessation. Sedentary, overweight/obese subjects were assigned to one of three 8-mo exercise programs: 1) low volume/moderate intensity [equivalent of ∼12 miles/wk, 1,200 kcal/wk at 40–55% peak O2 consumption (V̇o2peak), 200 min exercise/wk], 2) low volume/vigorous intensity (∼12 miles/wk, 1,200 kcal/wk at 65–80% V̇o2peak, 125 min/wk), and 3) high volume/vigorous intensity (∼20 miles/wk, 2,000 kcal/wk at 65–80% V̇o2peak, 200 min/wk). Insulin sensitivity (intravenous glucose tolerance test, SI) was measured when subjects were sedentary and at 16–24 h and 15 days after the final training bout. SI increased with training compared with the sedentary condition ( P ≤ 0.05) at 16–24 h with all of the exercise prescriptions. SI decreased to sedentary, pretraining values after 15 days of training cessation in the low-volume/vigorous-intensity group. In contrast, at 15 days SI was significantly elevated compared with sedentary ( P ≤ 0.05) in the prescriptions utilizing 200 min/wk (low volume/moderate intensity, high volume/vigorous intensity). In the high-volume/vigorous-intensity group, indexes of muscle mitochondrial density followed a pattern paralleling insulin action by being elevated at 15 days compared with pretraining; this trend was not evident in the low-volume/moderate-intensity group. These findings suggest that in overweight/obese subjects a relatively chronic persistence of enhanced insulin action may be obtained with endurance-oriented exercise training; this persistence, however, is dependent on the characteristics of the exercise training performed.

Effect of exercise on insulin action, glucose tolerance, and insulin secretion in aging

1990 ◽  
Vol 258 (6) ◽  
pp. E937-E943 ◽  
Author(s):  
S. E. Kahn ◽  
V. G. Larson ◽  
J. C. Beard ◽  
K. C. Cain ◽  
G. W. Fellingham ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
B Cell ◽  
Cell Function ◽  
Fasting Glucose ◽  
Oral Glucose ◽  
Intravenous Glucose ◽  
B Cell Function ◽  
Intravenous Glucose Tolerance

To assess the effect of exercise training on the insulin resistance and impaired pancreatic B-cell function of aging, we studied 13 healthy older men (ages 61-82 yr) before and after 6 mo intensive endurance exercise. An index of insulin sensitivity (SI) was measured using Bergman's minimal model. Intravenous glucose tolerance was quantified using the glucose disappearance constant (KGlc) while oral glucose tolerance was assessed after a 100-g glucose load. B-cell function was evaluated by measuring the acute insulin response (AIR) to glucose injection at fasting glucose (AIRGlc) and the AIR to arginine at multiple clamped glucose levels. Exercise produced an endurance training effect as demonstrated by an 18% increase in maximum O2 consumption (VO2max) [38.2 +/- 1.4 to 45.0 +/- 1.1 (SE) ml.kg fat-free mass-1.min-1, P less than 0.001]. An unchanged fasting glucose (5.3 +/- 0.2 to 5.4 +/- 0.2 mM) despite a reduced fasting insulin (61 +/- 6 to 48 +/- 6 pM, P less than 0.01) suggested exercise training improved insulin sensitivity. This was confirmed by a 36% increase in SI from 3.47 +/- 0.41 to 4.71 +/- 0.42 x 10(-5) min-1/pM (P = 0.01). Intravenous glucose tolerance did not change as measured by KGlc, which was 1.46 +/- 0.09 before and 1.48 +/- 0.16%/min after exercise training. Likewise, the incremental glucose response to oral glucose (633 +/- 49-618 +/- 45 mM.min) was unchanged. B-cell function was decreased as reflected by AIRGlc (351 +/- 73-245 +/- 53 pM, P less than 0.01) and the AIRArg at maximal glycemic potentiation (AIRmax, 1,718 +/- 260-1,228 +/- 191 pM, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

scholarly journals When MINMOD Artifactually Interprets Strong Insulin Secretion as Weak Insulin Action

2021 ◽  
Vol 12 ◽  
Author(s):  
Joon Ha ◽  
Ranganath Muniyappa ◽  
Arthur S. Sherman ◽  
Michael J. Quon
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Minimal Model ◽  
Insulin Response ◽  
Reference Method ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Intravenous Glucose ◽  
Model Studies ◽  
Increased Risk

We address a problem with the Bergman-Cobelli Minimal Model, which has been used for 40 years to estimate SI during an intravenous glucose tolerance test (IVGTT). During the IVGTT blood glucose and insulin concentrations are measured in response to an acute intravenous glucose load. Insulin secretion is often assessed by the area under the insulin curve during the first few minutes (Acute Insulin Response, AIR). The issue addressed here is that we have found in simulated IVGTTs, representing certain contexts, Minimal Model estimates of SI are inversely related to AIR, resulting in artifactually lower SI. This may apply to Minimal Model studies reporting lower SI in Blacks than in Whites, a putative explanation for increased risk of T2D in Blacks. The hyperinsulinemic euglycemic clamp (HIEC), the reference method for assessing insulin sensitivity, by contrast generally does not show differences in insulin sensitivity between these groups. The reason for this difficulty is that glucose rises rapidly at the start of the IVGTT and reaches levels independent of SI, whereas insulin during this time is determined by AIR. The minimal model in effect interprets this combination as low insulin sensitivity even when actual insulin sensitivity is unchanged. This happens in particular when high AIR results from increased number of readily releasable insulin granules, which may occur in Blacks. We conclude that caution should be taken when comparing estimates of SI between Blacks and Whites.

scholarly journals The Impact of Obesity On Insulin Sensitivity and Secretion During Pubertal Progression: A Longitudinal Study

2020 ◽  
Vol 105 (5) ◽  
pp. e2061-e2068 ◽  
Author(s):  
Megan M Kelsey ◽  
Laura Pyle ◽  
Allison Hilkin ◽  
Cameron D Severn ◽  
Kristina Utzschneider ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Response ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Normal Weight ◽  
Β Cell ◽  
Early Puberty ◽  
Intravenous Glucose ◽  
Increased Risk ◽  
The Impact

Abstract Context Physiologic changes in glucose metabolism are well-described to occur during puberty. However, there are important gaps in understanding the interaction between obesity and the normal physiologic changes during puberty, as well as how these changes could contribute to the increased risk of comorbidities, such as type 2 diabetes and dyslipidemia, in youth with obesity. Objective The objective of this study was to compare longitudinal changes in insulin sensitivity (Si) and secretion during pubertal progression in youth with obesity versus those with normal weight. Design Longitudinal observational study evaluating youth from early puberty (Tanner [T]2-T3) until puberty completion (T5). Setting Pediatric academic hospital Clinical Translational Research Center. Participants Pubertal youth with normal weight (n = 47; 22 female, 25 male) and obesity (n = 37; 23 female, 14 male) Main Outcome Measures Si, insulin response (acute insulin response to glucose, AIRg) and disposition index (DI) by intravenous glucose tolerance test at baseline (T2-T3), T4, and T5 Results Youth with obesity had significantly lower Si and higher AIRg at each time point (P &lt; 0.001), but DI was similar between the groups. There were no group differences in trajectory of Si, AIRg or DI over time. Leptin, insulin-like growth factor-1, and obesity were most strongly associated with Si and AIRg at all time points. Conclusions Obesity significantly impacts Si during puberty, even at the earliest stages. However, in general, obese youth have adequate β-cell compensation for the significantly reduced Si of puberty. Future studies are needed to better predict the subset of youth who fail to maintain β-cell compensation during puberty.

scholarly journals Increased Inflammation and Cardiometabolic Risk in Individuals with Low AMY1 Copy Numbers

2019 ◽  
Vol 8 (3) ◽  
pp. 382 ◽  
Author(s):  
Clara Marquina ◽  
Aya Mousa ◽  
Regina Belski ◽  
Harry Banaharis ◽  
Negar Naderpoor ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Fat Mass ◽  
Cardiometabolic Risk ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Copy Number Variations ◽  
Intravenous Glucose Tolerance Test ◽  
Healthy Population ◽  
Necrosis Factor Alpha ◽  
Intravenous Glucose

Lower copy number variations (CNVs) in the salivary amylase gene (AMY1) have been associated with obesity and insulin resistance; however, the relationship between AMY1 and cardiometabolic risk has not been fully elucidated. Using gold-standard measures, we aimed to examine whether AMY1 CNVs are associated with cardiometabolic risk factors in an overweight or obese, otherwise healthy population. Fifty-seven adults (58% male) aged 31.17 ± 8.44 years with a body mass index (BMI) ≥25 kg/m2 were included in the study. We measured AMY1 CNVs (qPCR); anthropometry (BMI; body composition by dual-energy X-ray absorptiometry); cardiovascular parameters (blood pressure, serum lipids by ELISA); insulin sensitivity (hyperinsulinaemic–euglycaemic clamp), insulin secretion (intravenous glucose tolerance test), and serum inflammation markers (multiplex assays). Based on previous studies and median values, participants were divided into low (≤4) and high (>4) AMY1 CNV groups. Low AMY1 carriers (n = 29) had a higher fat mass (40.76 ± 12.11 versus 33.33 ± 8.50 kg, p = 0.009) and LDL-cholesterol (3.27 ± 0.80 versus 2.87 ± 0.69 mmol/L, p = 0.038), and higher serum levels of interleukin [IL]-6, IL-1β, tumour necrosis factor-alpha and monocyte chemoattractant protein-1 (MCP-1) (all p < 0.05) compared with high AMY1 carriers (n = 28), but there were no differences in glycaemic measures, including insulin sensitivity or secretion (all p > 0.1). Except for MCP-1, the results remained significant in multivariable models adjusted for age, sex, and fat mass (all p < 0.05). Our findings suggest that low AMY1 CNVs are associated with increased cardiovascular disease risk and inflammation, but not glucose metabolism, in overweight or obese adults.

scholarly journals Effects of prolonged fasting and sustained lipolysis on insulin secretion and insulin sensitivity in normal subjects

2009 ◽  
Vol 296 (3) ◽  
pp. E454-E461 ◽  
Author(s):  
B. Salgin ◽  
M. L. Marcovecchio ◽  
S. M. Humphreys ◽  
N. Hill ◽  
L. J. Chassin ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Insulin Response ◽  
Random Order ◽  
Intravenous Glucose Tolerance Test ◽  
Disposition Index ◽  
Acute Insulin Response ◽  
Intravenous Glucose ◽  
Family History Of Diabetes ◽  
Prolonged Fast

Normal β-cells adjust their function to compensate for any decrease in insulin sensitivity. Our aim was to explore whether a prolonged fast would allow a study of the effects of changes in circulating free fatty acid (FFA) levels on insulin secretion and insulin sensitivity and whether any potential effects could be reversed by the antilipolytic agent acipimox. Fourteen (8 female, 6 male) healthy young adults (aged 22.8–26.9 yr) without a family history of diabetes and a body mass index of 22.6 ± 3.2 kg/m2 were studied on three occasions in random order. Growth hormone and FFA levels were regularly measured overnight (2200-0759), and subjects underwent an intravenous glucose tolerance test in the morning (0800-1100) on each visit. Treatment A was an overnight fast, treatment B was a 24-h fast with regular administrations of a placebo, and treatment C was a 24-h fast with regular ingestions of 250 mg of acipimox. The 24-h fast increased overnight FFA levels (as measured by the area under the curve) 2.8-fold [51.3 (45.6–56.9) vs. 18.4 (14.4–22.5) *104 μmol/l*min, P < 0.0001], and it led to decreases in insulin sensitivity [5.7 (3.6–8.9) vs. 2.6 (1.3–4.7) *10−4 min−1 per mU/l, P < 0.0001] and the acute insulin response [16.3 (10.9–21.6) vs. 12.7 (8.7–16.6) *102 pmol/l*min, P = 0.02], and therefore a reduction in the disposition index [93.1 (64.8–121.4) vs. 35.5 (21.6–49.4) *102 pmol/mU, P < 0.0001]. Administration of acipimox during the 24-h fast lowered FFA levels by an average of 20% (range: −62 to +49%; P = 0.03), resulting in a mean increase in the disposition index of 31% ( P = 0.03). In conclusion, the 24-h fast was accompanied by substantial increases in fasting FFA levels and induced reductions in the acute glucose-simulated insulin response and insulin sensitivity. The use of acipimox during the prolonged fast increased the disposition index, suggesting a partial reversal of the effects of fasting on the acute insulin response and insulin sensitivity.

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