SwePub
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:gup.ub.gu.se/321525"
 

Search: onr:"swepub:oai:gup.ub.gu.se/321525" > Hindbrain insulin c...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist
LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00007473naa a2200613 4500
001oai:gup.ub.gu.se/321525
003SwePub
008240528s2022 | |||||||||||000 ||eng|
0247 a https://gup.ub.gu.se/publication/3215252 URI
0247 a https://doi.org/10.1016/j.molmet.2022.1016142 DOI
040 a (SwePub)gu
041 a eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Eerola, Kim,d 1982u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut0 (Swepub:gu)xeerki
2451 0a Hindbrain insulin controls feeding behavior
264 1b Elsevier BV,c 2022
520 a Objective: Pancreatic insulin was discovered a century ago, and this discovery led to the first lifesaving treatment for diabetes. While still controversial, nearly one hundred published reports suggest that insulin is also produced in the brain, with most focusing on hypothalamic or cortical insulin-producing cells. However, specific function for insulin produced within the brain remains poorly understood. Here we identify insulin expression in the hindbrain's dorsal vagal complex (DVC), and determine the role of this source of insulin in feeding and metabolism, as well as its response to diet-induced obesity in mice. Methods: To determine the contribution of Ins2-producing neurons to feeding behavior in mice, we used the cross of transgenic RipHER-cre mouse and channelrhodopsin-2 expressing animals, which allowed us to optogenetically stimulate neurons expressing Ins2 in vivo. To confirm the presence of insulin expression in Rip-labeled DVC cells, in situ hybridization was used. To ascertain the specific role of insulin in effects discovered via optogenetic stimulation a selective, CNS applied, insulin receptor antagonist was used. To understand the physiological contribution of insulin made in the hindbrain a virogenetic knockdown strategy was used. Results: Insulin gene expression and presence of insulin-promoter driven fluorescence in rat insulin promoter (Rip)-transgenic mice were detected in the hypothalamus, but also in the DVC. Insulin mRNA was present in nearly all fluorescently labeled cells in DVC. Diet-induced obesity in mice altered brain insulin gene expression, in a neuroanatomically divergent manner; while in the hypothalamus the expected obesity-induced reduction was found, in the DVC diet-induced obesity resulted in increased expression of the insulin gene. This led us to hypothesize a potentially divergent energy balance role of insulin in these two brain areas. To determine the acute impact of activating insulin-producing neurons in the DVC, optic stimulation of light-sensitive channelrhodopsin 2 in Rip-transgenic mice was utilized. Optogenetic photoactivation induced hyperphagia after acute activation of the DVC insulin neurons. This hyperphagia was blocked by central application of the insulin receptor antagonist S961, suggesting the feeding response was driven by insulin. To determine whether DVC insulin has a necessary contribution to feeding and meta-bolism, virogenetic insulin gene knockdown (KD) strategy, which allows for site-specific reduction of insulin gene expression in adult mice, was used. While chow-fed mice failed to reveal any changes of feeding or thermogenesis in response to the KD, mice challenged with a high-fat diet consumed less food. No changes in body weight were identified, possibly resulting from compensatory reduction in thermogenesis. Conclusions: Together, our data suggest an important role for hindbrain insulin and insulin-producing cells in energy homeostasis. (c) 2022 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaper0 (SwePub)3012 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicine0 (SwePub)3012 hsv//eng
653 a Hindbrain
653 a Dorsal vagal complex
653 a Food intake
653 a Diet-induced obesity
653 a Insulin
653 a nucleus-tractus-solitarius
653 a central-nervous-system
653 a blood-brain-barrier
653 a intranasal insulin
653 a body-weight
653 a food-intake
653 a signaling mechanisms
653 a cerebrospinal-fluid
653 a alzheimers-disease
653 a gene-expression
653 a Endocrinology & Metabolism
7001 a Longo, Francescou Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut0 (Swepub:gu)xlongf
7001 a Reinbothe, Thomas,d 1981u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology4 aut0 (Swepub:gu)xreith
7001 a Richard, Jennifer E.u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut0 (Swepub:gu)xricje
7001 a Shevchouk, Olesyau Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut0 (Swepub:gu)xsheol
7001 a Lopez-Ferreras, Lorenau Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut
7001 a Mishra, Deveshu Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology4 aut
7001 a Asker, Mohammedu Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut0 (Swepub:gu)xaskmu
7001 a Tolö, Johan4 aut
7001 a Miranda, Carolineu Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut0 (Swepub:gu)xmirca
7001 a Saliha, Musovic,d 1990u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology4 aut0 (Swepub:gu)xmussa
7001 a Olofsson, Charlotta S,d 1971u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology4 aut0 (Swepub:gu)xoloch
7001 a Rorsman, Patrik,d 1959u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut0 (Swepub:gu)xrorpa
7001 a Skibicka, Karolina Pu Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut0 (Swepub:gu)xskika
7102 a Göteborgs universitetb Institutionen för neurovetenskap och fysiologi4 org
7730 t Molecular Metabolismd : Elsevier BVg 66q 66x 2212-8778
8564 8u https://gup.ub.gu.se/publication/321525
8564 8u https://doi.org/10.1016/j.molmet.2022.101614

Find in a library

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view