To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

In pancreatic islets from… - University of Gothenburg, Sweden Till startsida
Sitemap
To content Read more about how we use cookies on gu.se

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

Journal article
Authors V. Petrenko
Nikhil Gandasi
D. Sage
A. Tengholm
S. Barg
C. Dibner
Published in Proceedings of the National Academy of Sciences of the United States of America
Volume 117
Issue 5
Pages 2484-2495
ISSN 0027-8424
Publication year 2020
Published at Institute of Neuroscience and Physiology, Department of Physiology
Pages 2484-2495
Language en
Links dx.doi.org/10.1073/pnas.1916539117
Keywords circadian clock, exocytosis, human pancreatic islet, type 2 diabetes, real-time bioluminescence, glucose-homeostasis, clock, secretion, expression, rhythms, synchronization, identification, disruption, metabolism, obesity, Science & Technology - Other Topics
Subject categories Neurosciences

Abstract

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 alpha- and beta-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 ROR alpha/gamma, 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.

Page Manager: Webmaster|Last update: 9/11/2012
Share:

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?