bims-ciryme 2020-01-26 papers

Issue of 2020‒01‒26
two papers selected by
Gabriela Da Silva Xavier
University of Birmingham

Proc Natl Acad Sci U S A. 2020 Jan 21. pii: 201916539. [Epub ahead of print]

In pancreatic islets from type 2 diabetes patients, the dampened circadian oscillators lead to reduced insulin and glucagon exocytosis.

Volodymyr Petrenko, Nikhil R Gandasi, Daniel Sage, Anders Tengholm, Sebastian Barg, Charna Dibner.

Circadian clocks operative in pancreatic islets participate in the regulation of insulin secretion in humans and, if compromised, in the development of type 2 diabetes (T2D) in rodents. Here we demonstrate that human islet α- and β-cells that bear attenuated clocks exhibit strongly disrupted insulin and glucagon granule docking and exocytosis. To examine whether compromised clocks play a role in the pathogenesis of T2D in humans, we quantified parameters of molecular clocks operative in human T2D islets at population, single islet, and single islet cell levels. Strikingly, our experiments reveal that islets from T2D patients contain clocks with diminished circadian amplitudes and reduced in vitro synchronization capacity compared to their nondiabetic counterparts. Moreover, our data suggest that islet clocks orchestrate temporal profiles of insulin and glucagon secretion in a physiological context. This regulation was disrupted in T2D subjects, implying a role for the islet cell-autonomous clocks in T2D progression. Finally, Nobiletin, an agonist of the core-clock proteins RORα/γ, boosted both circadian amplitude of T2D islet clocks and insulin secretion by these islets. Our study emphasizes a link between the circadian clockwork and T2D and proposes that clock modulators hold promise as putative therapeutic agents for this frequent disorder.

Keywords: circadian clock; exocytosis; human pancreatic islet; real-time bioluminescence; type 2 diabetes

DOI: https://doi.org/10.1073/pnas.1916539117

Behav Brain Res. 2020 Jan 17. pii: S0166-4328(19)31517-7. [Epub ahead of print] 112471

Circadian modulation of motivation in mice.

Julieta Acosta, Ivana L Bussi, Macarena Esquivel, Christian Höcht, Diego A Golombek, Patricia V Agostino.

Most living organisms have a circadian timing system adapted to optimize the daily rhythm of exposure to the environment. This circadian system modulates several behavioral and physiological processes, including the response to natural and drug rewards. Food is the most potent natural reward across species. Food-seeking is known to be mediated by dopaminergic and serotonergic transmission in cortico-limbic pathways. In the present work, we show evidence of a circadian modulation of motivation for food reward in young (4-months old) and aged (over 1.5 years old) C57BL/6 mice. Motivation was assayed through the progressive ratio (PR) schedule. Mice under a 12:12 light/dark (LD) cycle exhibited a diurnal rhythm in motivation, becoming more motivated during the night, coincident with their active phase. This rhythm was also evident under constant dark conditions, indicating the endogenous nature of this modulation. However, circadian arrhythmicity induced by chronic exposure to constant light conditions impaired the performance in the task causing low motivation levels. Furthermore, the day/night difference in motivation was also evident even without caloric restriction when using a palatable reward. All these results were found to be unaffected by aging. Taken together, our results indicate that motivation for food reward is regulated in a circadian manner, independent of the nutritional status and the nature of the reward, and that this rhythmic modulation is not affected by aging. These results may contribute to improve treatment related to psychiatric disorders or drugs of abuse, taking into account potential mechanisms of circadian modulation of motivational states.

Keywords: Circadian system; Dopamine; Food reward; Motivation; Nucleus Accumbens

DOI: https://doi.org/10.1016/j.bbr.2020.112471