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Hormonal Regulation of Novel Glycogen Metabolic Proteins Hari Priya Vemana, Ehab M. Abo‐Ali, John L. Croft, Shraddha Bhutkar, Michael Woolford, Vikas V. DukhandeDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY, USA
Author(s) -
Vemana Hari Priya,
Abo-Ali Ehab M.,
Croft John L.,
Bhutkar Shradda,
Woolford Michael,
Dukhande Vikas V.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05008
Subject(s) - lafora disease , glycogen , endocrinology , biology , medicine , glycogen synthase , hormone , phosphatase , enzyme , biochemistry
Lafora disease (LD) is a rare autosomal recessive disorder manifesting as a progressive myoclonic epilepsy. LD is characterized by the formation of Lafora bodies, insoluble deposits containing abnormal glycogen‐like material in many tissues. LD is caused by mutations in the genes encoding dual‐specificity phosphatase laforin ( EPM2A) or the E3 ubiquitin ligase malin ( EPM2B / NHLRC1) . Several research studies on LD have shown that laforin functions as a phosphatase for glycogen. Malin forms a functional complex with laforin and either malin alone or the laforin‐malin complex is known to ubiquitinate multiple proteins involved in glycogen metabolism. It is well established that hormones such as insulin regulates glycogen metabolism but hormonal regulation of laforin and malin is not completely elucidated. In type‐2 diabetes, defects in insulin responsiveness leads to a state called insulin resistance. Our objective is to study the effect of hormones and nutrients on novel glycogen metabolic proteins laforin and malin in physiology and diabetes pathophysiology. We used liver cells in culture and a rodent model of diabetes using high‐fat diet and low dose streptozotocin (HF‐STZ). We measured gene expression, protein expression, protein posttranslational modifications, and functional activities of laforin and malin. Our preliminary data indicates that both diabetic conditions and insulin modulate the expression of LD proteins. Our ongoing studies are directed towards delineating the molecular mechanisms of these alterations. This study can serve to find novel potential targets for the pharmacotherapy of type‐2 diabetes. Support or Funding Information This study is supported by an award from National Institute of General Medical Sciences of the National Institute of Health, Award number: SC2GM125550.