Ekspresija i funkcija insulina u centralnom nervnom sistemu
Insulin expression and action in the central nervous system
Abstract
Nakon njegovog otkrića početkom dvadesetog veka, dugo je smatrano da se insulin isključivo sintetiše
u pankreasu i da u centralni nervni sistem (CNS) dospeva prolaskom kroz krvno-moždanu barijeru.
Međutim, razvojem molekularno-bioloških metoda potvrđeno je prisustvo iRNK za preporoinsulin, samog
(prepro)insulina, kao i C-peptida u nekim regionima mozga. Time je višestruko potvrđeno da se insulin,
osim u pankreasu, sintetiše i u CNS. Nakon otkrića da se i receptor za insulin eksprimira u CNS, ispitivanja
su bila usmerena ka upoznavanju dejstva ovog hormona u mozgu. Pokazano je da je, između ostalog,
uključen u kontrolu apetita, regulaciji reprodukcije, ali i procesa vezanih za učenje i konsolidaciju memorije.
Takođe je utvrđeno da su poremećaji dejstva insulina u CNS povezani sa razvojem nekih neurodegenerativnih
bolesti.
Iako je većina pomenutih efekata prvobitno pripisana insulinu koji iz sistemske cirkulacije dospeva u
CNS, sve više se dizajniraju studije koje su orijentisa...ne isključivo ka upoznavaju funkcije insulina koji nastaje
u mozgu. Do sada je pokazano da se produkcija insulina u hipotalamusu smanjuje tokom stresnih situacija,
što se negativno odražava na sintezu hormona rasta u adenohipofizi i njegovu sekreciju u sistemsku
cirkulaciju. Nasuprot tome, pokazano je da kratkotrajno gladovanje povećava ekspresiju insulina u neuronima
istog moždanog regiona ali i da ovaj fenomen nije povezan sa povećanjem stope ugradnje glukoznih
transportera u ćelijsku membranu, niti sinteze glikogena u astrocitima. Biće potrebno sprovesti
dodatne studije kako bi se u većoj meri upoznala uloga insulina koji nastaje unutar CNS.
After being discovered in the early twentieth century, insulin was long considered to be exclusively
produced in the β-pancreatic cells. Therefore the presence of this hormone in the central nervous system
(CNS) was accounted for solely by its transport across the blood-brain barrier. However, owing to the advances
in molecular biological techniques, it was established that the preproinsulin mRNA, the (pre)prounsulin
peptide and C-peptide were also present in the CNS parenchyma. These findings unequivocally proved
that, in addition to the pancreas, insulin was also produced in the CNS. After discovery that the insulin receptor
was also expressed in the brain, numerous studies aimed to discover the insulin actions within the
CNS. It was found that insulin was involved in the control of appetite, reproduction, learning and memory
consolidation. Moreover, it was confirmed that the impairment of insulin signaling within the certain brain
regions was associated with various neurode...generative disorders. Although these effects were initially assigned
to the action of the insulin transported from the circulation into the CNS, more studies were designed
to uncover the roles of insulin produced in the CNS. It has been shown so far that stress decreases
hypothalamic insulin production which subsequently results in the decreased growth hormone production
and its secretion form adenohypophysis. Furthermore, short-term fasting increased hypothalamic insulin
expression in rats, albeit this phenomenon did not result in either increased glucose uptake nor
glycogen production in this brain region. More studies are needed to fully elucidate the role of the centrally
produced insulin.
Keywords:
insulin / centralni nervni sistem / gladovanje / insulinska signalizacija / hipotalamus / central nervous system / fasting / insulin signaling / hypothalamusSource:
Trendovi u molekularnoj Biologiji, 2022, 2, 155-167Publisher:
- Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200178 (University of Belgrade, Faculty of Biology) (RS-MESTD-inst-2020-200178)
Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CHAP AU - Dakić, Tamara AU - Vujović, Predrag PY - 2022 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1819 AB - Nakon njegovog otkrića početkom dvadesetog veka, dugo je smatrano da se insulin isključivo sintetiše u pankreasu i da u centralni nervni sistem (CNS) dospeva prolaskom kroz krvno-moždanu barijeru. Međutim, razvojem molekularno-bioloških metoda potvrđeno je prisustvo iRNK za preporoinsulin, samog (prepro)insulina, kao i C-peptida u nekim regionima mozga. Time je višestruko potvrđeno da se insulin, osim u pankreasu, sintetiše i u CNS. Nakon otkrića da se i receptor za insulin eksprimira u CNS, ispitivanja su bila usmerena ka upoznavanju dejstva ovog hormona u mozgu. Pokazano je da je, između ostalog, uključen u kontrolu apetita, regulaciji reprodukcije, ali i procesa vezanih za učenje i konsolidaciju memorije. Takođe je utvrđeno da su poremećaji dejstva insulina u CNS povezani sa razvojem nekih neurodegenerativnih bolesti. Iako je većina pomenutih efekata prvobitno pripisana insulinu koji iz sistemske cirkulacije dospeva u CNS, sve više se dizajniraju studije koje su orijentisane isključivo ka upoznavaju funkcije insulina koji nastaje u mozgu. Do sada je pokazano da se produkcija insulina u hipotalamusu smanjuje tokom stresnih situacija, što se negativno odražava na sintezu hormona rasta u adenohipofizi i njegovu sekreciju u sistemsku cirkulaciju. Nasuprot tome, pokazano je da kratkotrajno gladovanje povećava ekspresiju insulina u neuronima istog moždanog regiona ali i da ovaj fenomen nije povezan sa povećanjem stope ugradnje glukoznih transportera u ćelijsku membranu, niti sinteze glikogena u astrocitima. Biće potrebno sprovesti dodatne studije kako bi se u većoj meri upoznala uloga insulina koji nastaje unutar CNS. AB - After being discovered in the early twentieth century, insulin was long considered to be exclusively produced in the β-pancreatic cells. Therefore the presence of this hormone in the central nervous system (CNS) was accounted for solely by its transport across the blood-brain barrier. However, owing to the advances in molecular biological techniques, it was established that the preproinsulin mRNA, the (pre)prounsulin peptide and C-peptide were also present in the CNS parenchyma. These findings unequivocally proved that, in addition to the pancreas, insulin was also produced in the CNS. After discovery that the insulin receptor was also expressed in the brain, numerous studies aimed to discover the insulin actions within the CNS. It was found that insulin was involved in the control of appetite, reproduction, learning and memory consolidation. Moreover, it was confirmed that the impairment of insulin signaling within the certain brain regions was associated with various neurodegenerative disorders. Although these effects were initially assigned to the action of the insulin transported from the circulation into the CNS, more studies were designed to uncover the roles of insulin produced in the CNS. It has been shown so far that stress decreases hypothalamic insulin production which subsequently results in the decreased growth hormone production and its secretion form adenohypophysis. Furthermore, short-term fasting increased hypothalamic insulin expression in rats, albeit this phenomenon did not result in either increased glucose uptake nor glycogen production in this brain region. More studies are needed to fully elucidate the role of the centrally produced insulin. PB - Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo T2 - Trendovi u molekularnoj Biologiji T1 - Ekspresija i funkcija insulina u centralnom nervnom sistemu T1 - Insulin expression and action in the central nervous system EP - 167 IS - 2 SP - 155 UR - https://hdl.handle.net/21.15107/rcub_imagine_1819 ER -
@inbook{ author = "Dakić, Tamara and Vujović, Predrag", year = "2022", abstract = "Nakon njegovog otkrića početkom dvadesetog veka, dugo je smatrano da se insulin isključivo sintetiše u pankreasu i da u centralni nervni sistem (CNS) dospeva prolaskom kroz krvno-moždanu barijeru. Međutim, razvojem molekularno-bioloških metoda potvrđeno je prisustvo iRNK za preporoinsulin, samog (prepro)insulina, kao i C-peptida u nekim regionima mozga. Time je višestruko potvrđeno da se insulin, osim u pankreasu, sintetiše i u CNS. Nakon otkrića da se i receptor za insulin eksprimira u CNS, ispitivanja su bila usmerena ka upoznavanju dejstva ovog hormona u mozgu. Pokazano je da je, između ostalog, uključen u kontrolu apetita, regulaciji reprodukcije, ali i procesa vezanih za učenje i konsolidaciju memorije. Takođe je utvrđeno da su poremećaji dejstva insulina u CNS povezani sa razvojem nekih neurodegenerativnih bolesti. Iako je većina pomenutih efekata prvobitno pripisana insulinu koji iz sistemske cirkulacije dospeva u CNS, sve više se dizajniraju studije koje su orijentisane isključivo ka upoznavaju funkcije insulina koji nastaje u mozgu. Do sada je pokazano da se produkcija insulina u hipotalamusu smanjuje tokom stresnih situacija, što se negativno odražava na sintezu hormona rasta u adenohipofizi i njegovu sekreciju u sistemsku cirkulaciju. Nasuprot tome, pokazano je da kratkotrajno gladovanje povećava ekspresiju insulina u neuronima istog moždanog regiona ali i da ovaj fenomen nije povezan sa povećanjem stope ugradnje glukoznih transportera u ćelijsku membranu, niti sinteze glikogena u astrocitima. Biće potrebno sprovesti dodatne studije kako bi se u većoj meri upoznala uloga insulina koji nastaje unutar CNS., After being discovered in the early twentieth century, insulin was long considered to be exclusively produced in the β-pancreatic cells. Therefore the presence of this hormone in the central nervous system (CNS) was accounted for solely by its transport across the blood-brain barrier. However, owing to the advances in molecular biological techniques, it was established that the preproinsulin mRNA, the (pre)prounsulin peptide and C-peptide were also present in the CNS parenchyma. These findings unequivocally proved that, in addition to the pancreas, insulin was also produced in the CNS. After discovery that the insulin receptor was also expressed in the brain, numerous studies aimed to discover the insulin actions within the CNS. It was found that insulin was involved in the control of appetite, reproduction, learning and memory consolidation. Moreover, it was confirmed that the impairment of insulin signaling within the certain brain regions was associated with various neurodegenerative disorders. Although these effects were initially assigned to the action of the insulin transported from the circulation into the CNS, more studies were designed to uncover the roles of insulin produced in the CNS. It has been shown so far that stress decreases hypothalamic insulin production which subsequently results in the decreased growth hormone production and its secretion form adenohypophysis. Furthermore, short-term fasting increased hypothalamic insulin expression in rats, albeit this phenomenon did not result in either increased glucose uptake nor glycogen production in this brain region. More studies are needed to fully elucidate the role of the centrally produced insulin.", publisher = "Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo", journal = "Trendovi u molekularnoj Biologiji", booktitle = "Ekspresija i funkcija insulina u centralnom nervnom sistemu, Insulin expression and action in the central nervous system", pages = "167-155", number = "2", url = "https://hdl.handle.net/21.15107/rcub_imagine_1819" }
Dakić, T.,& Vujović, P.. (2022). Ekspresija i funkcija insulina u centralnom nervnom sistemu. in Trendovi u molekularnoj Biologiji Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo.(2), 155-167. https://hdl.handle.net/21.15107/rcub_imagine_1819
Dakić T, Vujović P. Ekspresija i funkcija insulina u centralnom nervnom sistemu. in Trendovi u molekularnoj Biologiji. 2022;(2):155-167. https://hdl.handle.net/21.15107/rcub_imagine_1819 .
Dakić, Tamara, Vujović, Predrag, "Ekspresija i funkcija insulina u centralnom nervnom sistemu" in Trendovi u molekularnoj Biologiji, no. 2 (2022):155-167, https://hdl.handle.net/21.15107/rcub_imagine_1819 .