Intramyocellular lipid levels are associated with peripheral, but not hepatic, insulin sensitivity in normal healthy subjects

2009 ◽  
Vol 117 (3) ◽  
pp. 111-118 ◽  
Author(s):  
Burak Salgin ◽  
Alison J. Sleigh ◽  
Rachel M. Williams ◽  
Sarah J. Jackson ◽  
Les J. Bluck ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Fat Mass ◽  
Fat Free Mass ◽  
Whole Body ◽  
Glucose Disposal ◽  
Resonance Spectroscopy ◽  
Intramyocellular Lipid ◽  
1H Mrs ◽  
Euglycaemic Clamp ◽  
Hyperinsulinaemic Euglycaemic Clamp

Increased levels of IMCL (intramyocellular lipid) have been shown to be associated with reduced steady-state glucose infusion rates during a hyperinsulinaemic–euglycaemic clamp (M-value). The aim of the present study was to explore how IMCL levels relate to the insulin-mediated suppression of endogenous glucose production [hepatic SI (insulin sensitivity)] and increase in glucose disposal (peripheral SI). In the present study, 11 healthy young adults (7 male, 4 female; aged 21–31 years) undertook, in random order, an hyperinsulinaemic–euglycaemic clamp combined with stable glucose isotope enrichment to measure peripheral and hepatic SI, a 1H-MRS (proton-magnetic resonance spectroscopy) scan to determine IMCL levels and a DXA (dual-energy X-ray absorptiometry) scan to assess body composition. IMCL levels (range, 3.2–10.7) were associated with whole-body fat mass (r=0.787, P=0.004), fat mass corrected for height (r=0.822, P=0.002) and percentage of central fat mass (r=0.694, P=0.02), but were not related to whole-body FFM (fat-free mass; r=−0.472, P=0.1). IMCL levels correlated closely with the M-value (r=−0.727, P=0.01) and FFM-corrected peripheral SI (r=−0.675, P=0.02), but were not related to hepatic SI adjusted for body weight (r=0.08, P=0.8). The results of the present study suggest that IMCL accumulation may be a sensitive marker for attenuations in peripheral, but not hepatic, SI in normal populations. Given the close relationship of IMCL levels to whole-body and central abdominal fat mass, relative increases in the flux of lipids from adipose tissue to the intramyocellular compartment may be an integral part of the mechanisms underlying reductions in SI.

scholarly journals Longitudinal Changes in Insulin Resistance in Normal Weight, Overweight and Obese Individuals

2019 ◽  
Vol 8 (5) ◽  
pp. 623 ◽  
Author(s):  
Alice Tang ◽  
Adelle C. F. Coster ◽  
Katherine T. Tonks ◽  
Leonie K. Heilbronn ◽  
Nicholas Pocock ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Normal Weight ◽  
Liver Fat ◽  
Resonance Spectroscopy ◽  
Change Over Time ◽  
Euglycaemic Clamp ◽  
Hyperinsulinaemic Euglycaemic Clamp ◽  
Over Time

Background: Large cohort longitudinal studies have almost unanimously concluded that metabolic health in obesity is a transient phenomenon, diminishing in older age. We aimed to assess the fate of insulin sensitivity per se over time in overweight and obese individuals. Methods: Individuals studied using the hyperinsulinaemic-euglycaemic clamp at the Garvan Institute of Medical Research from 2008 to 2010 (n = 99) were retrospectively grouped into Lean (body mass index (BMI) < 25 kg/m2) or overweight/obese (BMI ≥ 25 kg/m2), with the latter further divided into insulin-sensitive (ObSen) or insulin-resistant (ObRes), based on median clamp M-value (M/I, separate cut-offs for men and women). Fifty-seven individuals participated in a follow-up study after 5.4 ± 0.1 years. Hyperinsulinaemic-euglycaemic clamp, dual-energy X-ray absorptiometry and circulating cardiovascular markers were measured again at follow-up, using the same protocols used at baseline. Liver fat was measured using computed tomography at baseline and proton magnetic resonance spectroscopy at follow-up with established cut-offs applied for defining fatty liver. Results: In the whole cohort, M/I did not change over time (p = 0.40); it remained significantly higher at follow-up in ObSen compared with ObRes (p = 0.02), and was not different between ObSen and Lean (p = 0.41). While BMI did not change over time (p = 0.24), android and visceral fat increased significantly in this cohort (ptime ≤ 0.0013), driven by ObRes (p = 0.0087 and p = 0.0001, respectively). Similarly, systolic blood pressure increased significantly over time (ptime = 0.0003) driven by ObRes (p = 0.0039). The best correlate of follow-up M/I was baseline M/I (Spearman’s r = 0.76, p = 1.1 × 10−7). Conclusions: The similarity in insulin sensitivity between the ObSen and the Lean groups at baseline persisted over time. Insulin resistance in overweight and obese individuals predisposed to further metabolic deterioration over time.

Increased intrahepatic triglyceride is associated with peripheral insulin resistance: in vivo MR imaging and spectroscopy studies

2007 ◽  
Vol 293 (6) ◽  
pp. E1663-E1669 ◽  
Author(s):  
Jong-Hee Hwang ◽  
Daniel T. Stein ◽  
Nir Barzilai ◽  
Min-Hui Cui ◽  
Julia Tonelli ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Magnetic Resonance ◽  
Subcutaneous Fat ◽  
Liver Fat ◽  
Whole Body ◽  
Glucose Disposal ◽  
Resonance Spectroscopy ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Triglyceride Accumulation

Recent studies have indicated that the mass/content of intramyocellular lipid (IMCL), intrahepatic triglyceride (IHTG), visceral fat (VF), and even deep abdominal subcutaneous fat (SF) may all be correlated with insulin resistance. Since simultaneous measurements of these parameters have not been reported, the relative strength of their associations with insulin action is not known. Therefore, the goals of this study were 1) to simultaneously measure IMCL, IHTG, VF, and abdominal SF in the same nondiabetic individuals using noninvasive 1H-magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) and 2) to examine how these fat stores are correlated with systemic insulin sensitivity as measured by whole body glucose disposal (Rd) during euglycemic-hyperinsulinemic clamp studies. Positive correlations were observed among IMCL, IHTG, and VF. There were significant inverse correlations between whole body Rd and both IMCL and VF. Notably, there was a particularly tight inverse correlation between IHTG and whole body Rd ( r = −0.86, P < 0.001), consistent with an association between liver fat and peripheral insulin sensitivity. This novel finding suggests that hepatic triglyceride accumulation has important systemic consequences that may adversely affect insulin sensitivity in other tissues.

Glucose tolerance and insulin action in healthy centenarians

1996 ◽  
Vol 270 (5) ◽  
pp. E890-E894 ◽  
Author(s):  
G. Paolisso ◽  
A. Gambardella ◽  
S. Ammendola ◽  
A. D'Amore ◽  
V. Balbi ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Insulin Action ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Fat Free Mass ◽  
Whole Body ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Aged Subjects

Advancing age has been found to be associated with a decline in insulin action. Nevertheless, no study has been conducted in healthy centenarians. Our study investigates glucose tolerance and insulin action in centenarians. Fifty-two subjects were enrolled. The subjects were divided in three groups as follows: 1) adults (< 50 yr; n = 20);2) aged subjects (> 75 yr; n = 22); and 3) centenarians (> 100 yr; n = 14). Body composition was studied by bioimpedance analysis. In all subjects, an oral glucose tolerance test and euglycemic glucose clamp were performed. Centenarians have a lower fat-free mass (FFM) than aged subjects and adults, whereas fasting plasma glucose, triglycerides, free fatty acids, urea, and creatinine were not different in the groups studies. Centenarians had a 2-h plasma glucose concentration (6.0 +/- 0.2 mmol/l) that was lower than that in aged subjects (6.6 +/- 0.5 mmol/l, P < 0.05) but not different from adults [6.4 +/- 0.4 mmol/l, P = not significant (NS)]. During the clamp, plasma glucose and insulin concentrations were similar in the three groups. In these conditions, centenarians had a whole body glucose disposal (34.1 +/- 0.6 mumol.kg FFM-1.min 1) that was greater than that in aged subjects (23.3 +/- 0.5 mumol.kg FFM-1.min-1 P < 0.01) but not different from adults (34.6 +/- 0.5 mumol/kg x min, P = NS). In conclusion, our study demonstrates that centenarians compared with aged subjects had a preserved glucose tolerance and insulin action.

scholarly journals GH effect on enzyme activity of 11βHSD in abdominal obesity is dependent on treatment duration

2006 ◽  
Vol 154 (1) ◽  
pp. 69-74 ◽  
Author(s):  
Helga Á Sigurjónsdóttir ◽  
Josef Koranyi ◽  
Magnus Axelson ◽  
Bengt-Åke Bengtsson ◽  
Gudmundur Johannsson
Keyword(s):  
Insulin Sensitivity ◽  
Abdominal Obesity ◽  
Fat Mass ◽  
Visceral Fat ◽  
Controlled Trial ◽  
Metabolic Effects ◽  
Glucose Disposal ◽  
Gh Treatment ◽  
Double Blind

Objective: In the past years the interaction of GH and 11βhydroxysteroid dehydrogenase (11βHSD) in the pathogenesis of central obesity has been suggested. Design: We studied the effects of 9 months of GH treatment on 11βHSD activity and its relationship with body composition and insulin sensitivity in 30 men with abdominal obesity, aged 48–66 years, in a randomised, double-blind, placebo-controlled trial. Methods: Urinary steroid profile was used to estimate 11βHSD type 1 and 2 (11βHSD1 and 11βHSD2) activities. Abdominal s.c. and visceral adipose tissues were measured using computed tomography. Glucose disposal rate (GDR) obtained during a euglycaemic–hyperinsulinaemic glucose clamp was used to assess insulin sensitivity. Results: In the GH-treated group the 11βHSD1 activity decreased transiently after 6 weeks (P < 0.01) whereas 11βHSD2 increased after 9 months of treatment (P < 0.05). Between 6 weeks and 9 months, GDR increased and visceral fat mass decreased. Changes in 11βHSD1 correlated with changes in visceral fat mass between baseline and 6 weeks. There were no significant correlations between 11βHSD1 and 11βHSD 2 and changes in GDR. Discussion: The study demonstrates that short- and long-term GH treatment has different effects on 11βHSD1 and 11βHSD2 activity. Moreover, the data do not support that long-term metabolic effects of GH are mediated through its action on 11βHSD.

scholarly journals Effects of isoenergetic overfeeding of either carbohydrate or fat in young men

2000 ◽  
Vol 84 (2) ◽  
pp. 233-245 ◽  
Author(s):  
Ole Lammert ◽  
Niels Grunnet ◽  
Peter Faber ◽  
Kirsten Schroll Bjørnsbo ◽  
John Dich ◽  
...  
Keyword(s):  
Fat Mass ◽  
De Novo ◽  
Fat Free Mass ◽  
Whole Body ◽  
Distribution Analysis ◽  
Mass Isotopomer Distribution Analysis ◽  
The Difference ◽  
Normal Men ◽  
Plasma Leptin ◽  
Mass Increase

Ten pairs of normal men were overfed by 5 MJ/d for 21 d with either a carbohydrate-rich or a fat-rich diet (C- and F-group). The two subjects in each pair were requested to follow each other throughout the day to ensure similar physical activity and were otherwise allowed to maintain normal daily life. The increase in body weight, fat free mass and fat mass showed great variation, the mean increases being 1·5 kg, 0·6 kg and 0·9 kg respectively. No significant differences between the C- and F-group were observed. Heat production during sleep did not change during overfeeding. The RQ during sleep was 0·86 and 0·78 in the C- and F-group respectively. The accumulated faecal loss of energy, DM, carbohydrate and protein was significantly higher in the C- compared with the F-group (30, 44, 69 and 51 % higher respectively), whereas the fat loss was the same in the two groups. N balance was not different between the C- and F-group and was positive. Fractional contribution from hepatic de novo lipogenesis, as measured by mass isotopomer distribution analysis after administration of [1-13C]acetate, was 0·20 and 0·03 in the C-group and the F-group respectively. Absolute hepatic de novo lipogenesis in the C-group was on average 211 g per 21 d. Whole-body de novo lipogenesis, as obtained by the difference between fat mass increase and dietary fat available for storage, was positive in six of the ten subjects in the C-group (mean 332 (SEM 191) g per 21 d). The change in plasma leptin concentration was positively correlated with the change in fat mass. Thus, fat storage during overfeeding of isoenergetic amounts of diets rich in carbohydrate or in fat was not significantly different, and carbohydrates seemed to be converted to fat by both hepatic and extrahepatic lipogenesis.

scholarly journals Plasma cathepsin D activity is negatively associated with hepatic insulin sensitivity in overweight and obese humans

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 374-384 ◽  
Author(s):  
Lingling Ding ◽  
Gijs H. Goossens ◽  
Yvonne Oligschlaeger ◽  
Tom Houben ◽  
Ellen E. Blaak ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Cathepsin D ◽  
Insulin Infusion ◽  
Hepatic Insulin Sensitivity ◽  
Euglycaemic Clamp ◽  
Negatively Associated ◽  
Peripheral Insulin Sensitivity ◽  
Hyperinsulinaemic Euglycaemic Clamp ◽  
Tnf Α ◽  
Glucose Output

Abstract Aims/hypothesis Insulin resistance in skeletal muscle and liver plays a major role in the pathophysiology of type 2 diabetes. The hyperinsulinaemic–euglycaemic clamp is considered the gold standard for assessing peripheral and hepatic insulin sensitivity, yet it is a costly and labour-intensive procedure. Therefore, easy-to-measure, cost-effective approaches to determine insulin sensitivity are needed to enable organ-specific interventions. Recently, evidence emerged that plasma cathepsin D (CTSD) is associated with insulin sensitivity and hepatic inflammation. Here, we aimed to investigate whether plasma CTSD is associated with hepatic and/or peripheral insulin sensitivity in humans. Methods As part of two large clinical trials (one designed to investigate the effects of antibiotics, and the other to investigate polyphenol supplementation, on insulin sensitivity), 94 overweight and obese adults (BMI 25–35 kg/m2) previously underwent a two-step hyperinsulinaemic–euglycaemic clamp (using [6,6-2H2]glucose) to assess hepatic and peripheral insulin sensitivity (per cent suppression of endogenous glucose output during the low-insulin-infusion step, and the rate of glucose disappearance during high-insulin infusion [40 mU/(m2 × min)], respectively). In this secondary analysis, plasma CTSD levels, CTSD activity and plasma inflammatory cytokines were measured. Results Plasma CTSD levels were positively associated with the proinflammatory cytokines IL-8 and TNF-α (IL-8: standardised β = 0.495, p < 0.001; TNF-α: standardised β = 0.264, p = 0.012). Plasma CTSD activity was negatively associated with hepatic insulin sensitivity (standardised β = −0.206, p = 0.043), independent of age, sex, BMI and waist circumference, but it was not associated with peripheral insulin sensitivity. However, plasma IL-8 and TNF-α were not significantly correlated with hepatic insulin sensitivity. Conclusions/interpretation We demonstrate that plasma CTSD activity, but not systemic inflammation, is inversely related to hepatic insulin sensitivity, suggesting that plasma CTSD activity may be used as a non-invasive marker for hepatic insulin sensitivity in humans.

scholarly journals Serum levels of 25 (OH) vitamin D in adults with obesity sarcopenia

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Maria Nikolova ◽  
Alexander Penkov
Keyword(s):  
Vitamin D ◽  
Body Composition ◽  
Fat Mass ◽  
Lean Mass ◽  
Fat Free Mass ◽  
Whole Body ◽  
Composition Analysis ◽  
Appendicular Lean Mass ◽  
Vitamin D Levels ◽  
25 Oh Vitamin D

AbstractIntroduction:Obesity has been linked with vitamin D deficiency in a number of cross-sectional studies, reviews and meta-analyses. To assess the correlations of plasma 25(OH) vitamin D levels with indices of body composition examined by DXA with an emphasis on lean and bone mass as well as on indices such as android/gynoid fat, appendicular lean mass (ALM) and appendicular lean mass index (ALMI), fat-mass indexes (FMI), fat-free mass indexes (FFMI) and the ALM-to-BMI index.Materials and Methods:62 adult subjects consented to participate – 27 men (43.5 %) and 35 women (56.5 %). Their mean age was 45.3 ± 9.5 years. Fan-beam dual-energy X-ray (DXA) body composition analysis was performed on a Lunar Prodigy Pro bone densitometer with software version 12.30. Vitamin D was measured by electro-hemi-luminescent detection as 25(OH)D Total (ECLIA, Elecsys 2010 analyzer, Roche Diagnostics). Statistical analyses were done using the SPSS 23.0 statistical package.Results:The serum 25(OH)D level was correlated significantly only to the whole body bone mineral content, the appendicular lean mass index (ALMI) and the ALM-to-BMI index, underlining a predominant role for lean and fat-free mass. Vitamin D showed a very weak correlation to % Body Fat and the Fat Mass Index (FMI) in men only. Moreover, the multiple regression equation including the associated parameters could explain only 7 % of the variation in the serum 25(OH)D levels.Discussion:Our conclusion was, that there are differences in the associations of the vitamin D levels with the different body composition indices, but these associations are generally very weak and therefore – negligible.

Effects of acute running exercise on whole body insulin action in obese male SHHF/Mcc-facp rats

1994 ◽  
Vol 77 (2) ◽  
pp. 534-541 ◽  
Author(s):  
J. Gao ◽  
W. M. Sherman ◽  
S. A. McCune ◽  
K. Osei
Keyword(s):  
Heart Failure ◽  
Insulin Sensitivity ◽  
Acute Exercise ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Whole Body ◽  
Glucose Disposal ◽  
Hepatic Glucose ◽  
Insulin Responsiveness ◽  
Obese Male

This study utilized the obese male spontaneously hypertensive heart failure rat (SHHF/Mcc-facp), which has metabolic features very similar to human non-insulin-dependent diabetes mellitus. The purpose of this study was to assess the insulin sensitivity and responsiveness of whole body glucose disposal and insulin suppressability of hepatic glucose production with use of the euglycemic-hyperinsulinemic clamp procedure in 12- to 15-wk-old SHHF/Mcc-facp rats at rest (OS) and 2.5 h after a single session of acute exercise (OE). Lean male SHHF/Mcc-facp rats were sedentary (LS) control animals. At least three clamps producing different insulin-stimulated responses were performed on each animal in a randomized order. At this age the obese animals are normotensive and have not developed congestive heart failure. Compared with LS, OS were significantly hyperglycemic and hyperinsulinemic and insulin sensitivity and responsiveness of whole body glucose uptake and insulin suppressability of hepatic glucose production were significantly decreased. Compared with LS and OS, acute exercise significantly decreased resting plasma glucose but did not alter plasma insulin. Compared with OS, acute exercise significantly increased the insulin responsiveness of whole body glucose disposal but did not affect the sensitivity of whole body glucose disposal or insulin suppressability of hepatic glucose production. Compared with LS, however, acute exercise did not “normalize” the insulin responsiveness of whole body glucose disposal. Thus a single acute exercise session improves but does not normalize whole body insulin resistance in the SHHF/Mcc-facp rat.

Determinants of insulin-stimulated glucose disposal in middle-aged, premenopausal women

2001 ◽  
Vol 281 (1) ◽  
pp. E113-E121 ◽  
Author(s):  
Michael J. Toth ◽  
Cynthia K. Sites ◽  
William T. Cefalu ◽  
Dwight E. Matthews ◽  
Eric T. Poehlman
Keyword(s):  
Physical Activity ◽  
Maximal Oxygen Consumption ◽  
Premenopausal Women ◽  
Abdominal Fat ◽  
Fat Free Mass ◽  
Thigh Muscle ◽  
Whole Body ◽  
Glucose Disposal ◽  
Statistical Control ◽  
Regional Adiposity

Controversy exists regarding the relative importance of adiposity, physical fitness, and physical activity in the regulation of insulin-stimulated glucose disposal. To address this issue, we measured insulin-stimulated glucose disposal [mg · kg fat-free mass (FFM)−1 · min−1; oxidative and nonoxidative components] in 45 nondiabetic, nonobese, premenopausal women (mean ± SD; 47 ± 3 yr) by use of hyperinsulinemic euglycemic clamp (40 mU · m−2 · min−1) and [6,6-2H2]glucose dilution techniques. We also measured body composition, abdominal fat distribution, thigh muscle fat content, maximal oxygen consumption (V˙o 2 max), and physical activity energy expenditure (2H2 18O kinetics) as possible correlates of glucose disposal.V˙o 2 max was the strongest correlate of glucose disposal ( r = 0.63, P < 0.01), whereas whole body and abdominal adiposity showed modest associations (range of r values from −0.32 to −0.46, P< 0.05 to P < 0.01). A similar pattern of correlations was observed for nonoxidative glucose disposal. None of the variables measured correlated with oxidative glucose disposal. The relationship of V˙o 2 max to glucose disposal persisted after statistical control for FFM, percent body fat, and intra-abdominal fat ( r = 0.40, P < 0.01). In contrast, correlations of total and regional adiposity measures to insulin sensitivity were no longer significant after statistical adjustment for V˙o 2 max.V˙o 2 max was the only variable to enter stepwise regression models as a significant predictor of total and nonoxidative glucose disposal. Our results highlight the importance ofV˙o 2 max as a determinant of glucose disposal and suggest that it may be a stronger determinant of variation in glucose disposal than total and regional adiposity in nonobese, nondiabetic, premenopausal women.

Acute elevation of plasma lipids does not affect ATP synthesis in human skeletal muscle

2010 ◽  
Vol 299 (1) ◽  
pp. E33-E38 ◽  
Author(s):  
A. Brehm ◽  
M. Krššák ◽  
A. I. Schmid ◽  
P. Nowotny ◽  
W. Waldhäusl ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Plasma Lipids ◽  
Atp Synthesis ◽  
Whole Body ◽  
Glucose Disposal ◽  
Resonance Spectroscopy ◽  
Lipid Infusion ◽  
Acute Elevation ◽  
Plasma Ffa ◽  
Early Effects

Prolonged elevation of plasma triglycerides and free fatty acids (FFA) reduces insulin-stimulated glucose disposal and myocellular flux through ATP synthase (fATPase). However, the early effects of lipids per se on fATPase are as yet unclear. Thus, this study examined glucose disposal and fATPase during 3 h of FFA elevation in the presence of low plasma insulinemia. Euglycemic pancreatic clamps with low-dose insulin supplementation (6 mU·m body surface area−2·min−1) were performed in eight healthy men with (LIP) or without (CON) lipid infusion to measure whole body glucose disposal. 31P/1H magnetic resonance spectroscopy of calf muscle was applied to quantify fATPase and concentrations of glucose 6-phosphate (G6P), inorganic phosphate (Pi), phosphocreatine (PCr), ADP, pH, and IMCL before and during the clamps. Lipid infusion increased plasma FFA approximately twofold and decreased glucose disposal by ∼50% (110–180 min: LIP 0.87 ± 0.45 vs. CON 1.75 ± 0.42 mg·kg−1·min−1, P = 0.002; means ± SD). Intramyocellular G6P tended to rise only under control conditions, whereas PCr, ADP, pH, and IMCL remained unchanged from fasting in LIP and CON. Although Pi concentrations increased by ∼18%, fATPase remained unchanged from fasting during the clamps (LIP 10.2 ± 2.2 vs. CON 10.5 ± 2.6 μmol·g muscle−1·min−1, P = not significant). We conclude that 3 h of lipid elevation fail to affect ATP synthesis despite marked reduction of whole body glucose uptake. This suggests that lipid-induced insulin resistance results primarily from mechanisms decreasing glucose uptake rather than from direct interference of fatty acid metabolites with mitochondrial function.

Sign in / Sign up

Export Citation Format

Share Document