Effects of insulin and dexamethasone on lipoprotein lipase in human adipose tissue

Appel, Burton; Fried, Susan K.

doi:10.1152/ajpendo.1992.262.5.e695

Cited by 49 publications

(40 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It seems unlikely, therefore, that the combination of dexamethasone and insulin contributed to the rise in serum leptin via an increase in adipocyte glucose utilization. This is in agreement with in vitro data showing that glucocorticoids tend to decrease human adipocyte glucose utilization (24,25).…”

Section: Discussionsupporting

confidence: 93%

A pulse of insulin and dexamethasone stimulates serum leptin in fasting human subjects

Laferrère

Caixàs²,

Fried³

et al. 2002

European Journal of Endocrinology

View full text Add to dashboard Cite

Objectives: We have previously shown that dexamethasone increases serum leptin in fed but not in fasted human subjects. We hypothesized that insulin and/or glucose mediated the effect of food intake. The primary aim of this study was to determine whether the administration of a pulse of insulin with dexamethasone was sufficient to increase serum leptin in vivo in fasted human subjects. Whether the presence of transient hyperglycemia and the dose of insulin were important was tested as a secondary aim. Methods: Twenty-nine normal subjects were studied. In experiment 1 (meal-like), a pulse of insulin (0.03 U/kg s.c.) and of dexamethasone (2 mg i.v.) was given, and the blood glucose transiently elevated to 50 mg/dl above baseline for the first 2 h. In experiments 2 and 3 (dose-response), the effect of two doses of insulin (0.03 U/kg in experiment 2 and 0.06 U/kg in experiment 3) was tested in combination with dexamethasone, this time without transient hyperglycemia. Nine subjects were studied under fasting conditions, with or without dexamethasone, as a control experiment. Results: A meal-like transient hyperinsulinemia and hyperglycemia, with a pulse of dexamethasone, increased serum leptin levels from baseline by 54^21% at 9 h ðP ¼ 0:038Þ: In the absence of transient hyperglycemia, leptin increased significantly after doses of both insulin and dexamethasone. The effect of insulin was dose-dependent, with a larger increment of serum leptin at 9 h after the highest dose of insulin ð75:2^15:7% vs 21:3^8:5%; P ¼ 0:013Þ. Fasting, with or without dexamethasone, resulted in a significant 20% decrease in leptin from morning basal levels. Conversely, the administration of a pulse of insulin and glucose, in the absence of dexamethasone, prevented the drop in serum leptin observed during fasting, regardless of the insulin dose or the serum glucose elevation. Conclusions: With the permissive effect of dexamethasone, a single pulse of insulin triggered a rise in serum leptin in humans, even in the absence of transient hyperglycemia. A single pulse of insulin with glucose can prevent the drop in serum leptin normally observed during fasting.

show abstract

Section: Discussionsupporting

confidence: 93%

A pulse of insulin and dexamethasone stimulates serum leptin in fasting human subjects

Laferrère

Caixàs²,

Fried³

et al. 2002

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…In the case of insulin, regulation through increased synthesis and release (58,59) of the protein from adipocyte to the endothelial cell surface have also been reported. Physiological doses of insulin and dexamethasone increased heparin-releasable LPL activity up to 8-fold and LPL synthesis up to 5-fold (57). By comparison, recent in vitro data suggest that, under physiological conditions, the extent of induction through the SREBP1 pathway in adipocytes is modest (2-3-fold) (53).…”

Section: Discussionmentioning

confidence: 93%

“…Despite this, much of the regulation of the enzyme protein occurs at the post-translational level (55). Insulin and dexamethasone have both been shown in vitro to up-regulate LPL activity markedly in adipocytes independently and synergistically, not only through the induction of LPL gene expression but quantitatively more importantly through post-transcriptional and post-translational regulations (56,57). In the case of insulin, regulation through increased synthesis and release (58,59) of the protein from adipocyte to the endothelial cell surface have also been reported.…”

Section: Discussionmentioning

confidence: 99%

Hypertriglyceridemia in Lecithin-cholesterol Acyltransferase-deficient Mice Is Associated with Hepatic Overproduction of Triglycerides, Increased Lipogenesis, and Improved Glucose Tolerance

Xie

Maguire

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Lecithin-cholesterol acyltransferase deficiency is frequently associated with hypertriglyceridemia (HTG) in animal models and humans. We investigated the mechanism of HTG in the ldlr؊/؊ ؋ lcat؊/؊ (double knockout (dko)) mice using the ldlr؊/؊ ؋ lcat؉/؉ (knock-out (ko)) littermates as control. Mean fasting triglyceride (TG) levels in the dko mice were elevated 1.75-fold compared with their controls (p < 0.002). Both the very low density lipoprotein and the low density lipoprotein/intermediate density lipoprotein fractions separated by fast protein liquid chromatography were TG-enriched in the dko mice. In vitro lipolysis assay revealed that the dko mouse very low density lipoprotein (d < 1.019 g/ml) fraction separated by ultracentrifugation was a more efficient substrate for lipolysis by exogenous bovine lipoprotein lipase. Post-heparin lipoprotein lipase activity was reduced by 61% in the dko mice. Hepatic TG production rate, determined after intravenous Triton WR1339 injection, was increased 8-fold in the dko mice. Hepatic mRNA levels of sterol regulatory element binding protein-1 (srebp-1) and its target genes acetyl-CoA carboxylase-1 (acc-1), fatty acid synthase (fas), and stearoyl-CoA desaturase-1 (scd-1) were significantly elevated in the dko mice compared with the ko control. The hepatic mRNA levels of LXR␣ (lxr␣) and its target genes including angiopoietin-like protein 3 (angptl-3) in the dko mice were unchanged. Fasting glucose and insulin levels were reduced by 31 and 42%, respectively in the dko mice, in conjunction with a 49% reduction in hepatic pepck-1 mRNA (p ‫؍‬ 0.014). Both the HTG and the improved fasting glucose phenotype seen in the dko mice are at least in part attributable to an up-regulation of the hepatic srebp-1c gene.

show abstract

“…LPL activity is regulated by several hormones including catecholamines, insulin, and steroids, as well as by certain cytokines (8,14,15), and serves as an appropriate marker of the overall lipogenic capacity of adipose tissue.…”

mentioning

confidence: 99%

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

et al. 2002

View full text Add to dashboard Cite

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.

show abstract

Effects of insulin and dexamethasone on lipoprotein lipase in human adipose tissue

Cited by 49 publications

References 27 publications

A pulse of insulin and dexamethasone stimulates serum leptin in fasting human subjects

A pulse of insulin and dexamethasone stimulates serum leptin in fasting human subjects

Hypertriglyceridemia in Lecithin-cholesterol Acyltransferase-deficient Mice Is Associated with Hepatic Overproduction of Triglycerides, Increased Lipogenesis, and Improved Glucose Tolerance

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

Contact Info

Product

Resources

About