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Updated: Aug 10, 2026

Extracellular Glucose Depletion as an Indirect Measure of Glucose Uptake in Cells and Tissues Ex Vivo
Published on: April 6, 2022
Dual effect of insulin on in vitro leptin secretion by adipose tissue
X Casabiell1, V Piñeiro, L F De la Cruz
1Endocrine Section, Hospital de Conxo, Spain. xcasab@lugo.usc.es
Insights
Insulin has a dual effect on leptin secretion: an early inhibition followed by later stimulation. This effect, dependent on glucose uptake, involves posttranslational modifications, not changes in ob mRNA levels.
Area of Science:
- Endocrinology
- Cell Biology
- Metabolism
Background:
- Insulin is widely accepted to stimulate leptin secretion.
- The precise mechanisms and temporal dynamics of insulin's effect on leptin are not fully elucidated.
Purpose of the Study:
- To investigate the temporal effects of insulin on leptin secretion in vitro.
- To determine the role of glucose metabolism in insulin-mediated leptin regulation.
Main Methods:
- Utilized a validated in vitro system to study adipose cells.
- Measured leptin secretion over time (0-96 hours) under varying glucose concentrations.
- Assessed the impact of glucose uptake inhibitors on leptin secretion.
- Analyzed ob mRNA levels to explore regulatory mechanisms.
Main Results:
- Observed a biphasic effect of insulin on leptin secretion: initial inhibition (<48h) followed by stimulation (48-96h).
- The stimulatory phase was dependent on physiological or supraphysiological glucose concentrations.
- Inhibition of glucose uptake abolished the stimulatory effect.
- No significant changes in ob mRNA levels were detected, indicating posttranslational regulation.
Conclusions:
- Insulin exerts a dual, time-dependent effect on adipose cell leptin secretion.
- Early insulin action inhibits leptin release, while later effects stimulate it, linked to increased glucose uptake and subsequent metabolic changes.
- Regulation of leptin secretion by insulin occurs at the posttranslational level.
Abstract:
Although it is widely accepted that insulin stimulates leptin secretion, a dual action was observed using a validated in vitro system, i.e., an early (less than 48 h) inhibitory action, followed later (48-96 h) by a clear-cut stimulation. While the inhibitory phase was observed at every glucose concentration tested (from 1 to 25 mM), the stimulatory phase required the presence of physiological or supraphysiological glucose concentrations. In fact, leptin secretion was virtually eliminated in the presence of glucose uptake inhibitors. This dual effect of insulin was not due to modifications of the ob mRNA levels, suggesting that it depends entirely on posttranslational mechanisms. In conclusion, insulin appears to induce an early inhibition of leptin secretion by the adipose cell, followed later by a stimulatory effect secondary to the metabolic changes triggered by the insulin-induced increase in glucose uptake.
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