Abstract
Diabetes Mellitus leads to pain neuropathy and cardiovascular complications which remain resistant to current therapies involving the control of glycaemia. This study aims at defining the contribution of kinin B1 receptor (B1R) and the oxidative stress on sensory abnormalities and arterial hypertension in a rat model of insulin resistance. Rats were fed with 10% d-glucose for a chronic period of 12-14 weeks and the impact of a diet supplemented with α-lipoic acid, a potent antioxidant, was determined on tactile and cold allodynia, arterial hypertension and the expression of kinin B1R (real-time PCR and autoradiography) in several tissues. Acute effects of brain penetrant (LF22-0542) and peripherally acting (R-715) B1R antagonists were also assessed. Glucose-fed rats exhibited tactile and cold allodynia along with increases in systolic blood pressure between 4 and 12 weeks; these alterations were alleviated by α-lipoic acid. The latter regimen also decreased significantly increased plasma levels of insulin and glucose and insulin resistance (HOMA index) at 14 weeks. B1R mRNA was virtually absent in liver, aorta, lung, kidney and spinal cord isolated from control rats, yet B1R mRNA was markedly increased in all tissues in glucose-fed rats. Up-regulated B1R mRNA and B1R binding sites (spinal cord) were significantly reduced by α-lipoic acid in glucose-fed rats. LF22-0542 reduced tactile and cold allodynia (3 h) and reversed arterial hypertension (3-48 h) in glucose-fed rats. R-715 abolished tactile and cold allodynia but had not effect on blood pressure. Data suggest that the oxidative stress contributes to the induction and up-regulation of B1R in the model of insulin resistance induced by glucose feeding. The over expressed B1R contributes centrally to arterial hypertension and in the periphery to sensory abnormalities.
Original language | English (US) |
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Pages (from-to) | 375-387 |
Number of pages | 13 |
Journal | Neuropeptides |
Volume | 41 |
Issue number | 6 |
DOIs | |
State | Published - Dec 2007 |
Externally published | Yes |
Keywords
- Allodynia
- Arterial hypertension
- B receptor
- Bradykinin
- Diabetes mellitus
- Insulin resistance
- Neuropathy
- Oxidative stress
- α-Lipoic acid
ASJC Scopus subject areas
- Endocrinology
- Neurology
- Endocrine and Autonomic Systems
- Cellular and Molecular Neuroscience