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.

Highlights

  • My laboratory has focused on the role of microvascular dysfunction in the development and progression of diabetic neuropathy

  • Treating diabetic rats with Alogliptin lowered serum thiobarbituric acid reactive substances (TBARS), but the difference was not significant compared to untreated diabetic rats

  • We previously reported that the inhibition of neutral endopeptidase was an efficacious treatment for vascular and neural complications in streptozotocin diabetic rats [20, 21]

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Summary

Introduction

My laboratory has focused on the role of microvascular dysfunction in the development and progression of diabetic neuropathy. In vivo dipeptidyl peptidase-IV degrades and inactivates glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) These incretin hormones are released by gut endocrine cells and play an important role in glucose homeostasis primarily by regulating blood glucose levels through stimulating glucose-dependent insulin secretion, reducing glucagon secretion and slowing of gastric emptying [4, 5]. The degradation of these peptides by dipeptidyl peptidase-IV is responsible for their short half life in circulation [4, 6]

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