Effect of combination therapy consisting of enalapril, α-lipoic acid, and menhaden oil on diabetic neuropathy in a high fat/low dose streptozotocin treated rat.
We have previously demonstrated that treating diabetic rats with enalapril, an angiotensin converting enzyme (ACE) inhibitor, α-lipoic acid, an antioxidant, or menhaden oil, a natural source of omega-3 fatty acids can partially improve diabetic peripheral neuropathy. In this study we sought to determine the efficacy of combining these three treatments on vascular and neural complications in a high fat fed low dose streptozotocin treated rat, a model of type 2 diabetes. Rats were fed a high fat diet for 8 weeks followed by a 30 mg/kg dose of streptozotocin. Eight weeks after the onset of hyperglycemia diabetic rats were treated with a combination of enalapril, α-lipoic acid and menhaden oil. Diabetic rats not receiving treatment were continued on the high fat diet. Glucose clearance was impaired in diabetic rats and significantly improved with treatment. Diabetes caused steatosis, elevated serum lipid levels, slowing of motor and sensory nerve conduction, thermal hypoalgesia, reduction in intraepidermal nerve fiber profiles, decrease in cornea sub-basal nerve fiber length and corneal sensitivity and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles of the sciatic nerve. Treating diabetic rats with the combination of enalapril, α-lipoic acid and menhaden oil reversed all these deficits to near control levels except for motor nerve conduction velocity which was also significantly improved compared to diabetic rats but remained significantly decreased compared to control rats. These studies suggest that a combination therapeutic approach may be most effective for treating vascular and neural complications of type 2 diabetes.
Department of Internal Medicine, University of Iowa, Iowa City, 52242 IA, USA.
Eric P
EP
Davidson
Department of Veterans Affairs Iowa City Health Care System, Iowa City, 52246 IA, USA.
Amey
A
Holmes
Department of Internal Medicine, University of Iowa, Iowa City, 52242 IA, USA.
Lawrence J
LJ
Coppey
Department of Veterans Affairs Iowa City Health Care System, Iowa City, 52246 IA, USA; Department of Internal Medicine, University of Iowa, Iowa City, 52242 IA, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, 52242 IA, USA. Electronic address: mark-yorek@uiowa.edu.
Mark A
MA
Yorek
D000818:Animals; D003315:Cornea / Q000294:innervation; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000209:etiology; D059305:Diet, High-Fat / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000627:therapeutic use*; D005395:Fish Oils / Q000008:administration & dosage / Q000627:therapeutic use*; D005951:Glucose Tolerance Test; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000098:blood supply; D013311:Streptozocin / Q000008:administration & dosage; D008063:Thioctic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects
D005395:Fish Oils; C033266:Menhaden oil; D013311:Streptozocin; D004656:Enalapril; D008063:Thioctic Acid
Corneal nerves; Enalapril; Insulin resistance; Menhaden oil; Peripheral neuropathy; Type 2 diabetes; α-lipoic acid