Abstract |
Both insulin-dependent (type 1) and insulin-independent ( type 2) diabetes are complex disorders characterized by symptomatic glucose intolerance due to either defective insulin secretion, insulin action or both. Unchecked hyperglycemia leads to a series of complications among which is painful diabetic neuropathy, for which the kinin system has been implicated. Here, we review and compare the profile of several experimental models of type 1 and 2 diabetes (chemically induced versus gene-prone) and the incidence of diabetic neuropathy upon aging. We discuss the efficacy of selective antagonists of the inducible bradykinin B1 receptor (BKB1-R) subtype against hyperalgesia assessed by various nociceptive tests. In either gene-prone models of type 1 and 2 diabetes, the incidence of hyperalgesia mostly precedes the development of hyperglycemia. The administration of insulin, achieving euglycemia, does not reverse hyperalgesia. Treatment with a selective BKB1-R antagonist does not affect basal nociception in most normal control rats, whereas it induces a significant time- and dose-dependent attenuation of hyperalgesia, or even restores nociceptive responses, in experimental diabetic neuropathy models. Diabetic hyperalgesia is absent in streptozotocin-induced type 1 diabetic BKB1-R knockout mice. Thus, selective antagonism of the inducible BKB1-R subtype may constitute a novel and potential therapeutic approach for the treatment of painful diabetic neuropathy.
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Authors | Bichoy H Gabra, Nathalie Berthiaume, Pierre Sirois, François Nantel, Bruno Battistini |
Journal | Biological chemistry
(Biol Chem)
Vol. 387
Issue 2
Pg. 127-43
(Feb 2006)
ISSN: 1431-6730 [Print] Germany |
PMID | 16497144
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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Chemical References |
- Anticonvulsants
- Bradykinin B1 Receptor Antagonists
- Receptor, Bradykinin B1
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Topics |
- Animals
- Anticonvulsants
(therapeutic use)
- Bradykinin B1 Receptor Antagonists
- Diabetes Mellitus, Type 1
(drug therapy, epidemiology, metabolism)
- Diabetes Mellitus, Type 2
(drug therapy, epidemiology, metabolism)
- Diabetic Neuropathies
(drug therapy)
- Disease Models, Animal
- Humans
- Hyperalgesia
(drug therapy, metabolism)
- Kallikrein-Kinin System
(physiology)
- Receptor, Bradykinin B1
(deficiency, metabolism)
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