title: Novel Molecular Mechanisms of TSC22D4 action in development of Diabetes Mellitus
creator: Demir, Sevgican
subject: ddc-570
subject: 570 Life sciences
description: The pathogenesis of Type 2 Diabetes (T2D) manifests itself with elevated blood glucose and insulin levels.  At the molecular level, dysregulations in the insulin signaling pathway cause disruptive cellular processes  modulated by distinct regulators. Akt plays a key role in the insulin signaling cascade regulating glucose and  lipid metabolism, cell survival and proliferation. In my Ph.D. project, I identified Transforming Growth Factor  β1 (TGFβ1) Stimulated Clone 22 D4 (TSC22D4) as a novel Akt-interacting protein. TSC22D4 interacts specifically  with Akt1 via its D2 domain, which is located in the intrinsically disordered region of TSC22D4. Starvation or  energy deprivation promotes TSC22D4-Akt1 interaction, while refeeding mice or stimulating cells with glucose  and insulin impairs the interaction. Having identified the interaction site of TSC22D4 with Akt1, we produced  the D2+TSC allele which constitutively interacts with Akt1, independent of nutrient availability. The strong  interaction of TSC22D4 and Akt1 (via D2+TSC allele) improves glucose handling, insulin sensitivity and lipid  accumulation in AAV-transduced TSC22D4hep-/- mice. Altogether, TSC22D4 plays a role in regulating insulin  signaling via interacting Akt and contributes to its function on glucose and lipid metabolism.
date: 2022
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserver/32543/1/PhD%20Thesis_Sevgican%20Demir_for%20publication.pdf
identifier: DOI:10.11588/heidok.00032543
identifier: urn:nbn:de:bsz:16-heidok-325435
identifier:   Demir, Sevgican  (2022) Novel Molecular Mechanisms of TSC22D4 action in development of Diabetes Mellitus.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/32543/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng