The antilipolytic effect of insulin in human adipose tissue in obesity, diabetes mellitus, hyperinsulinemia, and starvation

Arner, Peter; Bolinder, Jan; Engfeldt, Peter; Östman, Jan

doi:10.1016/0026-0495(81)90020-2

Cited by 110 publications

(53 citation statements)

References 31 publications

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“…Our findings are also consistent with previous studies investigating the effect of both chronic high insulin and glucose on mature rat adipocytes and differentiated 3T3-L1 adipocytes (7,25). These studies demonstrate that the combination of chronic high glucose and insulin stimulates lipolysis, which is in contrast to previous studies that have examined the acute effects by insulin (4,(21)(22)(23). In the present study, adipocytes treated with insulin for 48 h showed a dose-dependent increase in lipolysis, as assessed by glycerol release assay.…”

Section: Discussionsupporting

confidence: 92%

“…The acute effects of insulin dose (1-1,000 nmol/l) in the presence of norepinephrine reduced lipolysis in a dose-dependent manner, whereas insulin in the absence of norepinephrine had no significant effect on lipolytic rate (data not shown). These results reaffirmed previous acute lipolysis studies (4,(21)(22)(23). The effect of insulin and RSG on TNF-␣ secretion.…”

Section: Diabetes Vol 51 May 2002supporting

confidence: 90%

“…Insulin alone and in combination with RSG regulated LPL protein expression in a dose-dependent manner, comparable with short-term effects on adipose tissue (21,23). In addition, insulin cotreated with RSG enhanced both HSL and LPL protein expression more than insulin alone, shifting the insulin dose response to the left.…”

Section: Discussionmentioning

confidence: 88%

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Insulin and Rosiglitazone Regulation of Lipolysis and Lipogenesis in Human Adipose Tissue In Vitro

et al. 2002

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Lipolysis is an important process determining fuel metabolism, and insulin regulates this process in adipose tissue. The aim of this study was to investigate the long-term effects of insulin, an insulin enhancer (rosiglitazone [RSG]), and insulin in combination with RSG on the regulation of lipolysis and lipogenesis in human abdominal subcutaneous fat. Lipolysis and lipogenesis were assessed by protein expression studies of hormone-sensitive lipase (HSL) (84 kDa) and lipoprotein lipase (LPL) (56 kDa), respectively. In addition, lipolytic rate was assessed by glycerol release assay and tumor necrosis factor (TNF)-␣ release measured by enzyme-linked immunosorbent assay (n ‫؍‬ 12). In subcutaneous adipocytes, increasing insulin doses stimulated LPL expression, with maximal stimulation at 100 nmol/l insulin (control, 1.0 ؎ 0.0 [mean ؎ SE, protein expression relative to control]; 1 nmol/l insulin, 0.87 ؎ 0.13; 100 nmol/l insulin, 1.68 ؎ 0.19; P < 0.001). In contrast, insulin at the 100 nmol/l dose reduced the expression of HSL (100 nmol/l insulin, 0.49 ؎ 0.05; P < 0.05), while no significant reduction was observed at other doses. Higher doses of insulin stimulated both HSL (1,000 nmol/l insulin, 1.4 ؎ 0.07; P < 0.01) and LPL (control 1.00 ؎ 0.0; 1,000 nmol/l insulin, 2.66 ؎ 0.27; P < 0.01) protein expression. Cotreatment with RSG induced an increased dose response to insulin for LPL and HSL (P < 0.05); RSG alone also increased LPL and HSL expression (P < 0.05). Insulin stimulated TNF-␣ secretion in a dose-dependent manner (P < 0.01); the addition of RSG (10 ؊8 mol/l) reduced TNF-␣ secretion (P < 0.05). In summary, chronic treatment of human adipocytes with insulin stimulates lipolysis and LPL protein expression. The addition of RSG reduced the lipolytic rate and TNF-␣ secretion. The increase in lipolysis is not explained by changes in HSL expression. These data, therefore, may explain in part why hyperinsulinemia coexists with increased circulating nonesterified free fatty acids and increased adiposity in obese and/or type 2 diabetic patients.

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Section: Discussionsupporting

confidence: 92%

Section: Diabetes Vol 51 May 2002supporting

confidence: 90%

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Insulin and Rosiglitazone Regulation of Lipolysis and Lipogenesis in Human Adipose Tissue In Vitro

et al. 2002

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“…This lack of association in the Sikh group tends to support the above hypothesis. The question of the comparison of the relative sensitivities to insulin of glucose transport and antilipolysis in obesity and NIDDM has been addressed in a limited number of studies [64][65][66][67] where divergent sensitivities have been reported. The lipolytic action of insulin was reported to be maintained despite the loss of insulin sensitivity with respect to glucose homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Lack of association between central adiposity and lipaemia in UK Sikh men

et al. 2003

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OBJECTIVE: To determine whether the positive statistical associations between measures of total and regional adiposity and measures of glucose, insulin and triacylglycerol (TAG) metabolism reported in Caucasian men, are also observed in UK Sikhs. DESIGN: A matched cross-sectional study in which each volunteer provided a blood sample after a 12-h overnight fast and had anthropometric measurements taken. SUBJECTS: A total of 55 healthy Caucasian and 55 healthy UK Sikh men were recruited. The Caucasian and Sikh men were matched for age (48.7710.9 and 48.3710.0 y, respectively) and body mass index (BMI) (26.172.8 and 26.373.2 kg/m 2 , respectively). MEASUREMENTS: Anthropometric measurements were performed to assess total and regional fat depots. The concentrations of plasma total cholesterol, high-density cholesterol (HDL-C), low-density cholesterol (LDL-C) and small dense LDL (LDL3), TAG, glucose, fasting insulin (ins) and nonesterified fatty acids (NEFA) were analysed in fasted plasma. Surrogate measures of insulin resistance (HOMA-IR) and insulin sensitivity (RQUICKI) were calculated from insulin and glucose (HOMA-IR) and insulin, glucose and NEFA (RQUICKI) measurements. RESULTS: The Sikh men had significantly higher body fat, with the sum of the four skinfold measurements (Ssk) (P ¼ 0.0001) and subscapular skinfold value (P ¼ 0.009) higher compared with the Caucasian men. The Sikh volunteers also had characteristics of the metabolic syndrome: lower HDL-C (P ¼ 0.07), higher TAG (P ¼ 0.004), higher % LDL3 (P ¼ 0.0001) and insulin resistance (P ¼ 0.05 ). Both ethnic groups demonstrated positive correlations between insulin and waist circumference (Caucasian: r ¼ 0.661, P ¼ 0.0001; Sikh: r ¼ 0.477, P ¼ 0.0001). The Caucasian men also demonstrated significant positive correlations between central adiposity (r ¼ 0.275, P ¼ 0.04), other measures of adiposity (BMI and suprailiac skinfold) and plasma TAG, whereas the Sikh men showed no correlation for central adiposity (r ¼ 0.019, ns) and TAG with a trend to a negative relationship between other measures (Ssk and suprailiac) which reached near significance for subscapular skinfold and TAG (r ¼ À0.246, P ¼ 0.007). The expected positive association between insulin and TAG was observed in the Caucasian men (r ¼ 0.318, P ¼ 0.04) but not in the Sikh men (r ¼ 0.011, ns). CONCLUSIONS: In the Caucasian men, the expected positive association between plasma TAG and centralized body fat was observed. However, a lack of association between centralized, or any other measure of adiposity, and plasma TAG was observed in the matched Sikh men, although both ethnic groups showed the positive association between centralized body fat and insulin resistance, which was less strong for Sikhs. These findings in the Sikh men were not consistent with the hypothesis that there is a clear causal relationship between body fat and its distribution, insulin resistance, and lipid abnormalities associated with the metabolic syndrome, in this ethnic group.

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“…Measurements of HSL activity and lipolysis have been conducted in adipose tissue of obese and insulin-resistant individuals, two conditions that precede the development of type 2 diabetes mellitus. Whereas in vitro studies have not demonstrated increased HSL activity and lipolytic rates in obesity [7], others have reported reduced HSL mRNA and protein and maximal lipolytic rate in subcutaneous adipocytes obtained from obese subjects [8]. Additionally, obese subjects expressing the truncated HSL variant (80 M r ), exhibit lower maximal HSL activity and lipolytic rates.…”

Section: Introductionmentioning

confidence: 99%

Hormone-sensitive lipase is reduced in the adipose tissue of patients with type 2 diabetes mellitus: influence of IL-6 infusion

et al. 2004

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Aims/hypothesis: Type 2 diabetes mellitus is characterised by increased plasma NEFA and IL-6 concentrations, and IL-6 increases lipolysis in healthy men. We assessed the adipose tissue hormone-sensitive lipase (HSL) mRNA expression, protein expression and HSL activity in patients with type 2 diabetes mellitus, and determined the effect of IL-6 administration on these measures. Methods: Seven patients with type 2 diabetes mellitus (age 67±4 years, weight 87±7 kg) and six age-and weight-matched individuals visited the laboratory on two occasions. Subcutaneous adipose tissue biopsies and blood samples were obtained prior to and during 3 h of either saline or recombinant human IL-6 infusion. Results: HSL mRNA was reduced (p<0.05) by ∼40% in type 2 diabetes mellitus relative to control subjects, while HSL protein expression showed a tendency to be decreased (35%, p=0.09). HSL activity averaged 8.87±1.25 and 6.91±1.20 nmol min −1 mg −1 protein for control and type 2 diabetic subjects respectively (p<0.05). IL-6 administration increased (p<0.05) HSL mRNA 2-fold at 60 min in both groups, whereas HSL protein and activity were unaffected by IL-6. Plasma insulin was elevated (p<0.05) in patients with type 2 diabetes mellitus at rest and was blunted (p<0.05) during IL-6 infusion in both groups. Plasma glucagon and cortisol were elevated (p<0.05) by IL-6 in both groups. Conclusions/interpretation: Our data demonstrate that basal HSL is decreased in patients with type 2 diabetes mellitus, and this may be a consequence of elevated plasma insulin levels. We have also shown that IL-6 administration increases HSL gene expression, although it exerted no effect on HSL protein and activity. This disparity between mRNA, protein and enzyme activity may be a function either of the marked alterations in the hormonal milieu induced by IL-6 administration and/or of post-transcriptional events.

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The antilipolytic effect of insulin in human adipose tissue in obesity, diabetes mellitus, hyperinsulinemia, and starvation

Cited by 110 publications

References 31 publications

Insulin and Rosiglitazone Regulation of Lipolysis and Lipogenesis in Human Adipose Tissue In Vitro

Insulin and Rosiglitazone Regulation of Lipolysis and Lipogenesis in Human Adipose Tissue In Vitro

Lack of association between central adiposity and lipaemia in UK Sikh men

Hormone-sensitive lipase is reduced in the adipose tissue of patients with type 2 diabetes mellitus: influence of IL-6 infusion

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