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Robust Circadian Clocks Are Ticking in Beta and non-Beta Cells of Human Pancreatic Islets

C. Dibner, T. Mannic, D. Sage, S. Lemeille, D. Bosco, P. Salmon, C. Bauer, M. Unser, P. Halban, J. Philippe

Diabetologia, vol. 55, suppl. 1, pp. S115, October 2012.

Background and aims: Due to the emerging evidence of the pancreas clock impact on the islet function and on type 2 diabetes development as shown in rodents, we aimed to tackle the circadian clockwork in human islets. The oscillator properties were assessed in the intact islets, and as well as in β-cells.

Materials and methods: We established a system for long term bioluminescence recording in cultured human islets, employing lentivector gene delivery. β-cells were stably labeled by rat insulin2 promoter (RIP) fluorescent construct. Single islet/ cell oscillation profiles were measured by combined bioluminescence - fluorescence time lapse microscopy.

Results: Human islets exhibited robust self-sustained circadian oscillations of Bmal1-luciferase expression at the both populations and single islet levels, with the oscillation period of 23.6 and 23.9 hours respectively. Moreover, endogenous Bmal1 transcript expression was circadian in synchronized islets over 48 hours, and antiphasic to Reverba, Per2 and Dbp transcript circadian profiles. Importantly, single β- and non-β cells revealed oscillatory profiles well synchronized with each other.

Conclusion: We provide for the first time a compelling evidence for a robust cell autonomous clock ticking in human islets. Moreover, β-cells possess their own clocks oscillating in synchrony with non-β-cells in primary human islet cell culture.

AUTHOR="Dibner, C. and Mannic, T. and Sage, D. and Lemeille, S. and
        Bosco, D. and Salmon, P. and Bauer, C. and Unser, M. and Halban, P.
        and Philippe, J.",
TITLE="Robust Circadian Clocks Are Ticking in Beta and non-Beta Cells of
        Human Pancreatic Islets",
volume="55, Supplementum 1",

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