The effect of low-dose insulin on mechanical sensitivity and allodynia in type I diabetes neuropathy.
The pathogenesis of diabetic neuropathy is multifactorial, but in general hyperglycemia through polyol and protein glycation pathways is considered to be a key etiological factor. Most likely insulin deficiency, in experimentally induced type I diabetes, contributes to the development of diabetes neuropathy. The aim of this study was to evaluate the in vivo behavioral effect of low-dose insulin on diabetic neuropathy in rats through behavioral testing in hyperglycemic conditions. Mechanical sensitivity and allodynia were tested in streptozotocin (STZ)-induced diabetic rats. After diabetes and neuropathy induction, treatment with low-dose insulin normalized behavioral test results in 37 days, while severe hyperglycemia persisted. Although this study provided no evidence about the role of hypoinsulinemia in the etiology of diabetes neuropathy, the results confirmed that an insulin deficit with impaired insulin signaling and neurotrophic support, rather than hyperglycemia, plays an essential role in the pathophysiology of painful diabetic neuropathy.
Hoybergs
Yves M J J
YM
CNS Discovery Research, Johnson & Johnson Pharmaceutical Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium. yhoyberg@prdbe.jnj.com
Meert
Theo F
TF
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D007328:Insulin / Q000172:deficiency* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014855:Wallerian Degeneration / Q000378:metabolism / Q000503:physiopathology
D001786:Blood Glucose; D007328:Insulin; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents