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Difference between revisions of "Dolinar K"

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== MitoEAGLE Short-Term Scientific Mission ==
****: [[Short-Term_Scientific_Missions_MitoEAGLE#STSM_Grant_Period_4 |STSM Grant Period 4]]
::: '''Work Plan summary'''
::::  Aim & motivation: Skeletal muscle is the largest insulin-sensitive tissue in our body and the most important site for insulin-stimulated glucose uptake and utilization. Reduced sensitivity to insulin (insulin resistance) in skeletal muscle can lead to increased blood glucose and eventually to type 2 diabetes, one of the major health problems of modern society. One very promising target for the treatment of diabetes is AMP-activated protein kinase (AMPK). AMPK can reduce insulin resistance and stimulate insulin-independent glucose uptake in skeletal muscle. We have discovered that some antirheumatic drugs promote AMPK activation and stimulate glucose uptake in cultured skeletal muscle cells (unpublished data). Analysis of oxygen consumption and extracellular acidification using Seahorse XF Analyzer (unpublished data) has indicated that some clinically used drugs may act as uncouplers of mitochondrial oxidative phosphorylation. ::::  We hypothesize that uncoupling of mitochondria leads to energy stress, which activates AMPK, which in turn stimulates glucose uptake. My STSM in the laboratory of prof. Garcia-Roves would enable us to further examine effects of these antirheumatic drugs on mitochondria in cultured skeletal muscle cells as well as in permeabilized myofibers with high-resolution respirometry (HRR) using Oroboros O2k respirometer. In addition to gaining new results that would increase the value and impact of our research I would also learn techniques that we want to implement in our laboratory, including HRR.
::::  Contributions: We believe that research done during this STSM will in general expand the knowledge on mechanisms of action of antirheumatic drugs and, in particular, the knowledge on the effects of antirheumatic drugs on mitochondria in skeletal muscle cells of healthy and diabetic humans. In addition, techniques learned and skills acquired during this STSM would be used to implement HRR in our laboratory and would then be available to other researchers in our research community which would further promote research in the field of mitochondrial bioenergetics. Moreover, my training in HRR will include the participation in the “mouse soleus study” MITOEAGLE WG2 project as a beginner following the experimental procedure and guidelines described in the study.
:::: Techniques: If this STSM is approved, I will be able to learn how to perform HRR using Oroboros O2k respirometer and how to properly quantify content of mitochondria in cells and tissues.
::::  Work plan: First, we would set up and optimize protocol for analysis of cultured cells (rat skeletal muscle cells L6 and human primary skeletal muscle cells). Next, we would examine the effect of our drugs on mitochondria in these cells. Finally, we would like to examine the effect of our drugs on mitochondria in skeletal muscles from healthy and diabetic rodents and/or humans.

Revision as of 12:03, 10 December 2019


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COST Action CA15203 (2016-2021): MitoEAGLE
Evolution-Age-Gender-Lifestyle-Environment: mitochondrial fitness mapping


Dolinar K


MitoPedia topics: EAGLE 

COST: Member

COST WG2: WG2


Name Dolinar Klemen, Univ. dipl. biochem.
Institution Institute of Pathophysiology,

Faculty of Medicine,

University of Ljubljana, SI

Address Zaloška 4, 1000
City Ljubljana
State/Province
Country Slovenia
Email klemen.dolinar@mf.uni-lj.si
Weblink
O2k-Network Lab


Labels:



Publications

 PublishedReference
Jan 2021 PLoS One2021Jan V, Miš K, Nikolic N, Dolinar K, Petrič M, Bone A, Thoresen GH, Rustan AC, Marš T, Chibalin AV, Pirkmajer S (2021) Effect of differentiation, de novo innervation, and electrical pulse stimulation on mRNA and protein expression of Na+,K+-ATPase, FXYD1, and FXYD5 in cultured human skeletal muscle cells. PLoS One 16:e0247377.
Rajh 2016 PLOS ONE2016Rajh M, Dolinar K, Miš K, Pavlin M, Pirkmajer (2016) Medium renewal blocks antiproliferative effects of metformin in cultured MDA-MB-231 breast cancer cells. PLOS ONE 11:e0154747.

Abstracts

 PublishedReference
Dolinar 2020 MiP20202020
Dolinar Klemen
Pirkmajer 2019 MiP20192019
Sergej Pirkmajer
Effect of antirheumatic drugs on AMPK and mitochondrial respiration in skeletal muscle.


MitoEAGLE Short-Term Scientific Mission

Work Plan summary
Aim & motivation: Skeletal muscle is the largest insulin-sensitive tissue in our body and the most important site for insulin-stimulated glucose uptake and utilization. Reduced sensitivity to insulin (insulin resistance) in skeletal muscle can lead to increased blood glucose and eventually to type 2 diabetes, one of the major health problems of modern society. One very promising target for the treatment of diabetes is AMP-activated protein kinase (AMPK). AMPK can reduce insulin resistance and stimulate insulin-independent glucose uptake in skeletal muscle. We have discovered that some antirheumatic drugs promote AMPK activation and stimulate glucose uptake in cultured skeletal muscle cells (unpublished data). Analysis of oxygen consumption and extracellular acidification using Seahorse XF Analyzer (unpublished data) has indicated that some clinically used drugs may act as uncouplers of mitochondrial oxidative phosphorylation. :::: We hypothesize that uncoupling of mitochondria leads to energy stress, which activates AMPK, which in turn stimulates glucose uptake. My STSM in the laboratory of prof. Garcia-Roves would enable us to further examine effects of these antirheumatic drugs on mitochondria in cultured skeletal muscle cells as well as in permeabilized myofibers with high-resolution respirometry (HRR) using Oroboros O2k respirometer. In addition to gaining new results that would increase the value and impact of our research I would also learn techniques that we want to implement in our laboratory, including HRR.
Contributions: We believe that research done during this STSM will in general expand the knowledge on mechanisms of action of antirheumatic drugs and, in particular, the knowledge on the effects of antirheumatic drugs on mitochondria in skeletal muscle cells of healthy and diabetic humans. In addition, techniques learned and skills acquired during this STSM would be used to implement HRR in our laboratory and would then be available to other researchers in our research community which would further promote research in the field of mitochondrial bioenergetics. Moreover, my training in HRR will include the participation in the “mouse soleus study” MITOEAGLE WG2 project as a beginner following the experimental procedure and guidelines described in the study.
Techniques: If this STSM is approved, I will be able to learn how to perform HRR using Oroboros O2k respirometer and how to properly quantify content of mitochondria in cells and tissues.
Work plan: First, we would set up and optimize protocol for analysis of cultured cells (rat skeletal muscle cells L6 and human primary skeletal muscle cells). Next, we would examine the effect of our drugs on mitochondria in these cells. Finally, we would like to examine the effect of our drugs on mitochondria in skeletal muscles from healthy and diabetic rodents and/or humans.