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Human adipose cells in vitro are either refractory or responsive to insulin, reflecting host metabolic state.

Lizunov VA, Stenkula KG, Blank PS, Troy A, Lee JP, Skarulis MC, Cushman SW, Zimmerberg J - PLoS ONE (2015)

Bottom Line: Two statistically-defined populations best describe the observed cellular heterogeneity, representing the fractions of refractive and responsive adipose cells.Thus, a two-component model best describes the relationship between cellular refractory fraction and subject SI.Since isolated cells exhibit these different response characteristics in the presence of constant culture conditions and milieu, we suggest that a physiological switching mechanism at the adipose cellular level ultimately drives systemic SI.

View Article: PubMed Central - PubMed

Affiliation: Program in Physical Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States of America.

ABSTRACT
While intercellular communication processes are frequently characterized by switch-like transitions, the endocrine system, including the adipose tissue response to insulin, has been characterized by graded responses. Yet here individual cells from adipose tissue biopsies are best described by a switch-like transition between the basal and insulin-stimulated states for the trafficking of the glucose transporter GLUT4. Two statistically-defined populations best describe the observed cellular heterogeneity, representing the fractions of refractive and responsive adipose cells. Furthermore, subjects exhibiting high systemic insulin sensitivity indices (SI) have high fractions of responsive adipose cells in vitro, while subjects exhibiting decreasing SI have increasing fractions of refractory cells in vitro. Thus, a two-component model best describes the relationship between cellular refractory fraction and subject SI. Since isolated cells exhibit these different response characteristics in the presence of constant culture conditions and milieu, we suggest that a physiological switching mechanism at the adipose cellular level ultimately drives systemic SI.

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The average insulin response of the population of adipose cells (measured per subject) is determined by the change in the fraction of refractory cells, defined as the basal-like fraction present in the insulin stimulated state and derived from distributional fitting of individual subject insulin responses.The average values for both mobility (a) and fusion (b) rates measured for populations of cells was linearly correlated with the fraction of refractory cells. (c) The correlation between refractory fractions determined from mobility and fusion data (R2 = 0.67) does not pass through the origin.
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pone.0119291.g008: The average insulin response of the population of adipose cells (measured per subject) is determined by the change in the fraction of refractory cells, defined as the basal-like fraction present in the insulin stimulated state and derived from distributional fitting of individual subject insulin responses.The average values for both mobility (a) and fusion (b) rates measured for populations of cells was linearly correlated with the fraction of refractory cells. (c) The correlation between refractory fractions determined from mobility and fusion data (R2 = 0.67) does not pass through the origin.

Mentions: Interestingly, the average response of the population of adipose cells (measured per subject) is almost exclusively determined by the change in the fraction of refractory and responding cells. The average values for both mobility and fusion rates measured for populations of adipose cells have a linear dependence on the fraction of refractory cells (Fig. 8 A, B). Linear correlations between the average cell response and the fraction of refractory cells across the whole range of subjects with SI from 0.16 to 11 indicate that the average response is determined primarily by the change in the fraction of refractory cells rather than by a change in the amplitude of the response of non-refractory cells. Indeed, if the number of refractory adipose cells increases, it is expected to result in a lower average response for a cell population. However, this is only true if the underlying distribution parameters of the cellular responses (i.e. characteristic peak values for refractory and responding cells) do not change significantly with SI, which is exactly the case with GSV mobility and fusion rates.


Human adipose cells in vitro are either refractory or responsive to insulin, reflecting host metabolic state.

Lizunov VA, Stenkula KG, Blank PS, Troy A, Lee JP, Skarulis MC, Cushman SW, Zimmerberg J - PLoS ONE (2015)

The average insulin response of the population of adipose cells (measured per subject) is determined by the change in the fraction of refractory cells, defined as the basal-like fraction present in the insulin stimulated state and derived from distributional fitting of individual subject insulin responses.The average values for both mobility (a) and fusion (b) rates measured for populations of cells was linearly correlated with the fraction of refractory cells. (c) The correlation between refractory fractions determined from mobility and fusion data (R2 = 0.67) does not pass through the origin.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4359092&req=5

pone.0119291.g008: The average insulin response of the population of adipose cells (measured per subject) is determined by the change in the fraction of refractory cells, defined as the basal-like fraction present in the insulin stimulated state and derived from distributional fitting of individual subject insulin responses.The average values for both mobility (a) and fusion (b) rates measured for populations of cells was linearly correlated with the fraction of refractory cells. (c) The correlation between refractory fractions determined from mobility and fusion data (R2 = 0.67) does not pass through the origin.
Mentions: Interestingly, the average response of the population of adipose cells (measured per subject) is almost exclusively determined by the change in the fraction of refractory and responding cells. The average values for both mobility and fusion rates measured for populations of adipose cells have a linear dependence on the fraction of refractory cells (Fig. 8 A, B). Linear correlations between the average cell response and the fraction of refractory cells across the whole range of subjects with SI from 0.16 to 11 indicate that the average response is determined primarily by the change in the fraction of refractory cells rather than by a change in the amplitude of the response of non-refractory cells. Indeed, if the number of refractory adipose cells increases, it is expected to result in a lower average response for a cell population. However, this is only true if the underlying distribution parameters of the cellular responses (i.e. characteristic peak values for refractory and responding cells) do not change significantly with SI, which is exactly the case with GSV mobility and fusion rates.

Bottom Line: Two statistically-defined populations best describe the observed cellular heterogeneity, representing the fractions of refractive and responsive adipose cells.Thus, a two-component model best describes the relationship between cellular refractory fraction and subject SI.Since isolated cells exhibit these different response characteristics in the presence of constant culture conditions and milieu, we suggest that a physiological switching mechanism at the adipose cellular level ultimately drives systemic SI.

View Article: PubMed Central - PubMed

Affiliation: Program in Physical Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States of America.

ABSTRACT
While intercellular communication processes are frequently characterized by switch-like transitions, the endocrine system, including the adipose tissue response to insulin, has been characterized by graded responses. Yet here individual cells from adipose tissue biopsies are best described by a switch-like transition between the basal and insulin-stimulated states for the trafficking of the glucose transporter GLUT4. Two statistically-defined populations best describe the observed cellular heterogeneity, representing the fractions of refractive and responsive adipose cells. Furthermore, subjects exhibiting high systemic insulin sensitivity indices (SI) have high fractions of responsive adipose cells in vitro, while subjects exhibiting decreasing SI have increasing fractions of refractory cells in vitro. Thus, a two-component model best describes the relationship between cellular refractory fraction and subject SI. Since isolated cells exhibit these different response characteristics in the presence of constant culture conditions and milieu, we suggest that a physiological switching mechanism at the adipose cellular level ultimately drives systemic SI.

Show MeSH
Related in: MedlinePlus