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In pancreatic islet...
In pancreatic islets from type 2 diabetes patients, the dampened circadian oscillators lead to reduced insulin and glucagon exocytosis
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- Petrenko, V. (författare)
- Univ Geneva, Dept Med, Div Endocrinol Diabet & Nutr, CH-1211 Geneva, Switzerland;Univ Geneva, Fac Med, Dept Cell Physiol & Metab, CH-1211 Geneva, Switzerland;Univ Geneva, Fac Med, Diabet Ctr, CH-1211 Geneva, Switzerland;Univ Geneva, Inst Genet & Genom Geneva, CH-1211 Geneva, Switzerland
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- Gandasi, Nikhil (författare)
- Uppsala universitet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,Institutionen för medicinsk cellbiologi,Univ Goteborg, Inst Neurosci & Physiol, Dept Physiol, SE-40530 Gothenburg, Sweden
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- Sage, D. (författare)
- Ecole Polytech Fed Lausanne, Biomed Imaging Grp, CH-1015 Lausanne, Switzerland
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- Tengholm, Anders, 1971- (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Barg, Sebastian, 1969- (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Dibner, C. (författare)
- Univ Geneva, Dept Med, Div Endocrinol Diabet & Nutr, CH-1211 Geneva, Switzerland;Univ Geneva, Fac Med, Dept Cell Physiol & Metab, CH-1211 Geneva, Switzerland;Univ Geneva, Fac Med, Diabet Ctr, CH-1211 Geneva, Switzerland;Univ Geneva, Inst Genet & Genom Geneva, CH-1211 Geneva, Switzerland
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(creator_code:org_t)
- 2020-01-21
- 2020
- Engelska.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:5, s. 2484-2495
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- 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
- circadian clock
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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