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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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Related in: MedlinePlus

“Bee swarm” plots of single cell GSV mobility (a) and fusion (b) rates measured in the basal and insulin-stimulated states are consistent with two populations in the insulin-stimulated state in which one population matches the basal state.The “bee swarm” plots were created using the plotSpread function (by Jonas) and the cluster boundaries were calculated using the K-means clustering function, both within the program MATLAB. Cumulative distributions calculated for GSV mobility (c) and fusion (d) rates pooled from basal (black) and insulin stimulated (red) cells from all subjects. Basal CDFs were described by a single zero-truncated Gaussian cumulative distribution, while both CDFs for insulin stimulated mobility and fusion data were characterized by the sum of two zero-truncated Gaussian cumulative distributions.
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pone.0119291.g004: “Bee swarm” plots of single cell GSV mobility (a) and fusion (b) rates measured in the basal and insulin-stimulated states are consistent with two populations in the insulin-stimulated state in which one population matches the basal state.The “bee swarm” plots were created using the plotSpread function (by Jonas) and the cluster boundaries were calculated using the K-means clustering function, both within the program MATLAB. Cumulative distributions calculated for GSV mobility (c) and fusion (d) rates pooled from basal (black) and insulin stimulated (red) cells from all subjects. Basal CDFs were described by a single zero-truncated Gaussian cumulative distribution, while both CDFs for insulin stimulated mobility and fusion data were characterized by the sum of two zero-truncated Gaussian cumulative distributions.

Mentions: To better visualize the cellular response distributions, we present the pooled data as “bee swarm” plots (Fig. 4 A-B) that clearly illustrate the bimodal nature of the data. We observed two distinct populations for both the insulin-stimulated mobility and fusion rate data, with one of these populations coinciding with the basal state; we refer to this latter subpopulation as “insulin-refractory” (Fig. 4A-B).


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)

“Bee swarm” plots of single cell GSV mobility (a) and fusion (b) rates measured in the basal and insulin-stimulated states are consistent with two populations in the insulin-stimulated state in which one population matches the basal state.The “bee swarm” plots were created using the plotSpread function (by Jonas) and the cluster boundaries were calculated using the K-means clustering function, both within the program MATLAB. Cumulative distributions calculated for GSV mobility (c) and fusion (d) rates pooled from basal (black) and insulin stimulated (red) cells from all subjects. Basal CDFs were described by a single zero-truncated Gaussian cumulative distribution, while both CDFs for insulin stimulated mobility and fusion data were characterized by the sum of two zero-truncated Gaussian cumulative distributions.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0119291.g004: “Bee swarm” plots of single cell GSV mobility (a) and fusion (b) rates measured in the basal and insulin-stimulated states are consistent with two populations in the insulin-stimulated state in which one population matches the basal state.The “bee swarm” plots were created using the plotSpread function (by Jonas) and the cluster boundaries were calculated using the K-means clustering function, both within the program MATLAB. Cumulative distributions calculated for GSV mobility (c) and fusion (d) rates pooled from basal (black) and insulin stimulated (red) cells from all subjects. Basal CDFs were described by a single zero-truncated Gaussian cumulative distribution, while both CDFs for insulin stimulated mobility and fusion data were characterized by the sum of two zero-truncated Gaussian cumulative distributions.
Mentions: To better visualize the cellular response distributions, we present the pooled data as “bee swarm” plots (Fig. 4 A-B) that clearly illustrate the bimodal nature of the data. We observed two distinct populations for both the insulin-stimulated mobility and fusion rate data, with one of these populations coinciding with the basal state; we refer to this latter subpopulation as “insulin-refractory” (Fig. 4A-B).

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