Effect of enriching the diet with menhaden oil or daily treatment with resolvin D1 on neuropathy in a mouse model of type 2 diabetes.
The purpose of this study was to determine the effect of supplementing the diet of a mouse model of type 2 diabetes with menhaden (fish) oil or daily treatment with resolvin D1 on diabetic neuropathy. The end points evaluated included motor and sensory nerve conduction velocity, thermal sensitivity, innervation of sensory nerves in the cornea and skin, and the retinal ganglion cell complex thickness. Menhaden oil is a natural source for n-3 polyunsaturated fatty acids, which have been shown to have beneficial effects in other diseases. Resolvin D1 is a metabolite of docosahexaenoic acid and is known to have anti-inflammatory and neuroprotective properties. To model type 2 diabetes, mice were fed a high-fat diet for 8 wk followed by a low dosage of streptozotocin. After 8 wk of hyperglycemia, mice in experimental groups were treated for 6 wk with menhaden oil in the diet or daily injections of 1 ng/g body wt resolvin D1. Our findings show that menhaden oil or resolvin D1 did not improve elevated blood glucose, HbA1C, or glucose utilization. Untreated diabetic mice were thermal hypoalgesic, had reduced motor and sensory nerve conduction velocities, had decreased innervation of the cornea and skin, and had thinner retinal ganglion cell complex. These end points were significantly improved with menhaden oil or resolvin D1 treatment. Exogenously, resolvin D1 stimulated neurite outgrowth from primary cultures of dorsal root ganglion neurons from normal mice. These studies suggest that n-3 polyunsaturated fatty acids derived from fish oil could be an effective treatment for diabetic neuropathy.
Department of Internal Medicine, University of Iowa, Iowa City, Iowa;
Hanna
H
Shevalye
Department of Veterans Affairs Iowa City Health Care System, Iowa City, Iowa; Veterans Affairs Center for the Prevention and Treatment of Visual Loss, Iowa City, Iowa; and mark-yorek@uiowa.edu.
Matthew S
MS
Yorek
Department of Internal Medicine, University of Iowa, Iowa City, Iowa;
Lawrence J
LJ
Coppey
Department of Veterans Affairs Iowa City Health Care System, Iowa City, Iowa;
Amey
A
Holmes
Department of Veterans Affairs Iowa City Health Care System, Iowa City, Iowa; Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa; Veterans Affairs Center for the Prevention and Treatment of Visual Loss, Iowa City, Iowa; and.
Matthew M
MM
Harper
Department of Veterans Affairs Iowa City Health Care System, Iowa City, Iowa; Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa; Veterans Affairs Center for the Prevention and Treatment of Visual Loss, Iowa City, Iowa; and.
Randy H
RH
Kardon
Department of Veterans Affairs Iowa City Health Care System, Iowa City, Iowa; Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Veterans Affairs Center for the Prevention and Treatment of Visual Loss, Iowa City, Iowa; and Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa.
Mark A
MA
Yorek
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003315:Cornea / Q000294:innervation / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000178:diet therapy / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2; D003929:Diabetic Neuropathies / Q000178:diet therapy* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D059305:Diet, High-Fat; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005395:Fish Oils / Q000008:administration & dosage*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000178:diet therapy / Q000188:drug therapy / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D009431:Neural Conduction / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D012165:Retinal Ganglion Cells / Q000473:pathology; D012867:Skin / Q000294:innervation / Q000473:pathology
D000893:Anti-Inflammatory Agents; D005395:Fish Oils; D018696:Neuroprotective Agents; C518399:resolvin D1; C033266:Menhaden oil; D004281:Docosahexaenoic Acids
corneal nerve fibers; diabetic neuropathy; epidermal nerve fibers; fish oil; resolvin; type 2 diabetes