The Yorek Lab
The Yorek lab's research focuses primarily on vascular and neural disease related to obesity and diabetes. We are interested in determining the etiology of peripheral neuropathy associated with these conditions. An overall goal of our studies is to determine the role of vascular dysfunction in obesity- and diabetic-induced peripheral neuropathy and the mechanism responsible for vascular dysfunction. Briefly, the group has developed the methodology to examine the effect of diabetes on vasodilation of blood vessels that provide circulation to the sciatic nerve and the retina. Combined with the examination of motor and sensory nerve conduction velocity, neuronal blood flow in the sciatic nerve, and sensory nerve perception we are investigating the etiology of diabetic neuropathy with emphasis on vascular disease.
Visualization of Corneal Nerves
In addition, we have also been conducting studies examining impairment of innervation of the cornea as a marker for obesity- and diabetic-neuropathy. Using animal models of obesity and diabetes our group has demonstrated that loss of corneal nerves especially those innervating the cornea epithelium occurs early in disease. We have also shown that in the sub-epithelial layer of the cornea early detection of nerve loss can be achieved by examining the region of the whorl. These results have translational importance for the early detection of obesity- and diabetic-induced peripheral neuropathy that could be used for examining the progression and repair of neuropathy in patients. In this regard the lab has been conducting studies in the use of menhaden oil (fish oil), a natural source for n-3 fatty acids, for the treatment of obesity- and diabetic-induced peripheral neuropathy. Our studies have demonstrated that treating rodent models of pre-diabetes and types 1 and 2 diabetes with menhaden oil improves insulin resistance and vascular and neural complications.
We have also shown that treating type 2 diabetic mice with resolvin D1 can improve diabetic peripheral neuropathy. We believe that the mechanism(s) responsible for the beneficial effects of menhaden oil is the reduction in inflammatory stress and production of resolvins and neuroprotectin, metabolites of n-3 fatty acids that have anti-inflammatory and neuroprotection properties. Studies are ongoing to investigate the mechanism(s) responsible for the beneficial effects of fish oils in obesity and diabetes. In addition clinical studies are being designed to test the benefits of fish oil treatment in subjects with diabetes.
(Left to Right) Lawrence Coppey, Alex Obrosov, Mark Yorek, Eric Davidson, Hanna Shevalye
Is Fish Oil a Potential Treatment for Diabetic Peripheral Neuropathy? Yorek MA. Curr Diabetes Rev. 2017 May 22. doi: 10.2174/1573399813666170522155327. [Epub ahead of print] PMID: 28530530
- Impaired Corneal Sensation and Nerve Loss in a Type 2 Rat Model of Chronic Diabetes Is Reversible With Combination Therapy of Menhaden Oil, α-Lipoic Acid, and Enalapril.
Davidson EP, Coppey LJ, Shevalye H, Obrosov A, Kardon RH, Yorek MA.
Cornea. 2017 Jun;36(6):725-731. doi: 10.1097/ICO.0000000000001182.
- Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction.
Qi W, Keenan HA, Li Q, Ishikado A, Kannt A, Sadowski T, Yorek MA, Wu IH, Lockhart S, Coppey LJ, Pfenninger A, Liew CW, Qiang G, Burkart AM, Hastings S, Pober D, Cahill C, Niewczas MA, Israelsen WJ, Tinsley L, Stillman IE, Amenta PS, Feener EP, Vander Heiden MG, Stanton RC, King GL.
Nat Med. 2017 Apr 24. doi: 10.1038/nm.4328. [Epub ahead of print]
- Effect of tempol on peripheral neuropathy in diet-induced obese and high fat fed/low dose streptozotocin treated C57Bl6/J mice.
Obrosov A, Shevalye H, Coppey LJ, Yorek MA.
Free Radic Res. 2017 Apr 4:1-22. doi: 10.1080/10715762.2017.1315767. [Epub ahead of print]
- Early vs. late intervention of high fat/low dose streptozotocin treated C57Bl/6J mice with enalapril, α-lipoic acid, menhaden oil or their combination: Effect on diabetic neuropathy related endpoints.
Yorek MS, Obrosov A, Shevalye H, Coppey LJ, Kardon RH, Yorek MA.
Neuropharmacology. 2016 Dec 23;116:122-131. doi: 10.1016/j.neuropharm.2016.12.022. [Epub ahead of print]
- Effect of Treatment with Salsalate, Menhaden Oil, Combination of Salsalate and Menhaden Oil, or Resolvin D1 of C57Bl/6J Type 1 Diabetic Mouse on Neuropathic Endpoints.
Yorek MS, Coppey LJ, Shevalye H, Obrosov A, Kardon RH, Yorek MA.
J Nutr Metab. 2016;2016:5905891.
- Effect of Inhibition or Deletion of Neutral Endopeptidase on Neuropathic Endpoints in High Fat Fed/Low Dose Streptozotocin-Treated Mice.
Yorek MS, Obrosov A, Lu B, Gerard C, Kardon RH, Yorek MA.
J Neuropathol Exp Neurol. 2016 Sep 15. pii: nlw083. [Epub ahead of print]
- Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice.
Trammell SA, Weidemann BJ, Chadda A, Yorek MS, Holmes A, Coppey LJ, Obrosov A, Kardon RH, Yorek MA, Brenner C.
Sci Rep. 2016 May 27;6:26933. doi: 10.1038/srep26933.
- Corneal Sensitivity to Hyperosmolar Eye Drops: A Novel Behavioral Assay to Assess Diabetic Peripheral Neuropathy.
Yorek MS, Davidson EP, Poolman P, Coppey LJ, Obrosov A, Holmes A, Kardon RH, Yorek MA.
Invest Ophthalmol Vis Sci. 2016 May 1;57(6):2412-9. doi: 10.1167/iovs.16-19435.