Heterogeneity and contact-dependent regulation of hormone secretion by individual B cells

Salomon, Denis; Meda, Paolo

doi:10.1016/0014-4827(86)90354-x

Cited by 251 publications

(222 citation statements)

References 20 publications

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“…Beta cell heterogeneity in terms of insulin secretion has been described in rodents [10,21,26] and is described here for the first time in humans. In rodents, beta cell heterogeneity was also observed in terms of metabolic, signalling [27,28] and biosynthetic activities [12,29].…”

Section: Discussionmentioning

confidence: 80%

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Insulin secretion from human beta cells is heterogeneous and dependent on cell-to-cell contacts

Wojtusciszyn

Armanet²,

Morel³

et al. 2008

Diabetologia

124

102

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Aims/hypothesis We assessed the heterogeneity of insulin secretion from human isolated beta cells and its regulation by cell-to-cell contacts. Methods Insulin secretion from single and paired cells was assessed by a reverse haemolytic plaque assay. The percentage of plaque-forming cells, the mean plaque area and the total plaque development were evaluated after 1 h of stimulation with different secretagogues. Results Not all beta cells were surrounded by a haemolytic plaque under all conditions tested. A small fraction of the beta cell population (20%) secreted more than 90% and 70% of total insulin at 2.2 and 22.2 mmol/l glucose, respectively. Plaque-forming cells, mean plaque area and total plaque development were increased at 12.2 and 22.2 compared with 2.2 mmol/l glucose. Insulin secretion of single beta cells was similar at 12.2 and 22.2 mmol/l glucose. Insulin secretion of beta cell pairs was increased compared with that of single beta cells and was higher at 22.2 than at 12.2 mmol/l glucose. Insulin secretion of beta cells in contact with alpha cells was also increased compared with single beta cells, but was similar at 22.2 compared with 12.2 mmol/l glucose. Delta and other non-beta cells did not increase insulin secretion of contacting beta cells compared with that of single beta cells. Differences in insulin secretion between 22.2 and 12.2 mmol/l glucose were observed in murine but not in human islets. Conclusions/interpretation Human beta cells are highly heterogeneous in terms of insulin secretion so that a small fraction of beta cells contributes to the majority of insulin secreted. Homologous and heterologous intercellular contacts have a significant impact on insulin secretion and this could be related to the particular architecture of human islets.

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Section: Discussionmentioning

confidence: 80%

“…To this end, human islets isolated from different pancreases were dissociated and insulin secretion from single beta cells and aggregated cell pairs comprising beta and non-beta cells were studied by a reverse haemolytic plaque assay (RHPA) [21].…”

Section: Introductionmentioning

confidence: 99%

Insulin secretion from human beta cells is heterogeneous and dependent on cell-to-cell contacts

Wojtusciszyn

Armanet²,

Morel³

et al. 2008

Diabetologia

124

102

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“…Insulin secretion of b-cells was assessed by a RHPA, as previously described (Salomon & Meda 1986, Bosco & Meda 1998. Briefly, b-cells were diluted in KRB buffer supplemented with 0 .…”

Section: Insulin Secretion By Rhpamentioning

confidence: 99%

“…Insulin secretion from b-cell subpopulations sorted according to their E-cadherin expression Due to the above-described heterogeneity of E-cadherin expression and to the well-known heterogeneity of insulin secretion from isolated b-cells (Salomon & Meda 1986, Bosco et al 1989, we wondered whether there was a correlation between E-cadherin expression and insulin secretion. To address this, b-cells were sorted according to their E-cadherin expression as illustrated in Fig.…”

Section: Heterogeneous Expression Of E-cadherin At the Surface Of B-cmentioning

confidence: 99%

Differential expression of E-cadherin at the surface of rat β-cells as a marker of functional heterogeneity

Bosco¹,

Rouiller²,

Halban³

2007

Journal of Endocrinology

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The aim of this study was to assess whether the expression of E-cadherin at the surface of rat b-cells is regulated by insulin secretagogues and correlates with insulin secretion. When cultured under standard conditions, virtually all b-cells expressed E-cadherin observed by immunofluorescence, but heterogeneous staining was observed. Using fluorescence-activated cell sorting (FACS), two b-cell sub-populations were sorted: one that was poorly labeled ('ECad-low') and another that was highly labeled ('ECad-high'). After 1-h stimulation with 16 . 7 mM glucose, insulin secretion (reverse hemolytic plaque assay) from individual ECad-high b-cells was higher than that from ECad-low b-cells. Ca 2C-dependent b-cell aggregation was increased at 16 . 7 mM glucose when compared with 2 . 8 mM glucose. E-cadherin at the surface of b-cells was increased after 18 h at 11 . 1 and 22 . 2 mM glucose when compared with 2 . 8 mM glucose, with the greatest increase at 22 . 2 mM glucoseC0 . 5 mM isobutylmethylxanthine (IBMX).While no labeling was detected on freshly trypsinized cells, the proportion of stained cells increased in a time-dependent manner during culture for 1, 3, and 24 h. This recovery was faster when cells were incubated at 16 . 7 vs 2 . 8 mM glucose. Cycloheximide inhibited expression of E-cadherin at 2 . 8 mM glucose, but not at 16 . 7 mM, while depolymerization of actin by either cytochasin B or latrunculin B increased surface Ecadherin at low glucose. In conclusion, these results show that expression of E-cadherin at the surface of islet b-cells is controlled by secretagogues including glucose, correlates with insulin secretion, and can serve as a surface marker of b-cell function.

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“…Even in diabetic conditions, the percentage of CART-positive beta cells does not exceed 60%. The reasons for this heterogeneity are unknown but this situation is reminiscent of the variability of placental lactogen-induced serotonin immunoreactivity in individual beta cells [26,27], and of the variability in glucose responsiveness of individual beta cells [28,29]. Heterogeneity of proliferation, gene expression and the function of beta cells between islets as a result of differential blood flow has also been documented in the rat [30].…”

Section: Cart and Pancreatic Isletsmentioning

confidence: 99%

Cocaine- and amphetamine-regulated transcript: a novel regulator of energy homeostasis expressed in a subpopulation of pancreatic islet cells

Gilon

2016

Diabetologia

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Heterogeneity and contact-dependent regulation of hormone secretion by individual B cells

Cited by 251 publications

References 20 publications

Insulin secretion from human beta cells is heterogeneous and dependent on cell-to-cell contacts

Insulin secretion from human beta cells is heterogeneous and dependent on cell-to-cell contacts

Differential expression of E-cadherin at the surface of rat β-cells as a marker of functional heterogeneity

Cocaine- and amphetamine-regulated transcript: a novel regulator of energy homeostasis expressed in a subpopulation of pancreatic islet cells

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