Abstract
We sought to determine the effect of dipeptidyl peptidase IV (DPP-IV) inhibition on streptozotocin diabetes-induced vascular and neural dysfunction. After 4 weeks of untreated diabetes, rats were treated for 12 weeks with Alogliptin (DPP-IV inhibitor). Diabetes caused a slowing of motor and sensory nerve conduction velocity, thermal hypoalgesia, reduction in intraepidermal nerve fiber density in the hindpaw, and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles. Treatment significantly improved motor nerve conduction velocity and thermal response latency. Sensory nerve conduction velocity was marginally improved with treatment of diabetic rats, and treatment did not improve the decrease in intraepidermal nerve fiber density. Vascular relaxation by epineurial arterioles to calcitonin gene-related peptide but not acetylcholine was significantly improved with treatment. These studies suggest that some but not all vascular and neural complications associated with type 1 diabetes can be improved with the inhibition of DPP-IV activity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Blood Glucose / drug effects
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Blood Glucose / metabolism
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Diabetes Mellitus, Experimental / blood
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Diabetes Mellitus, Experimental / complications
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Diabetes Mellitus, Experimental / drug therapy*
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Diabetes Mellitus, Experimental / physiopathology
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Diabetes Mellitus, Type 1 / blood
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Diabetes Mellitus, Type 1 / complications
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Diabetes Mellitus, Type 1 / drug therapy*
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Diabetes Mellitus, Type 1 / physiopathology
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Diabetic Angiopathies / blood
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Diabetic Angiopathies / drug therapy*
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Diabetic Angiopathies / etiology
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Diabetic Angiopathies / physiopathology
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Diabetic Neuropathies / blood
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Diabetic Neuropathies / drug therapy*
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Diabetic Neuropathies / etiology
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Diabetic Neuropathies / physiopathology
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Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
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Hypoglycemic Agents / pharmacology*
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Male
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Motor Neurons / drug effects
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Neural Conduction / drug effects
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Oxidative Stress / drug effects
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Pain Measurement
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Pain Threshold / drug effects
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Piperidines / pharmacology*
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Rats
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Rats, Sprague-Dawley
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Sensory Receptor Cells / drug effects
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Time Factors
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Uracil / analogs & derivatives*
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Uracil / pharmacology
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Vasodilation / drug effects
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Weight Gain / drug effects
Substances
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Blood Glucose
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Dipeptidyl-Peptidase IV Inhibitors
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Hypoglycemic Agents
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Piperidines
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Uracil
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alogliptin