Журнал диабета и клинической практики

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Global Diabetes 2016: A correlative relationship between chronic pain and insulin resistance in Zucker fatty rats: role of down regulation of insulin receptors

Shuxing Wang

Epidemiological studies and meta-analyses report a strong relationship between chronic pain and abnormalities in glucose metabolism, but the exact relationship between chronic pain and insulin resistance in type-2-diabetes (T2D) remains unknown. Using a model of neuropathic thermal and tactile hypersensitivity induced by chronic constriction sciatic nerve injury (CCI) in Zucker diabetic fatty (ZDF) and Zucker lean (ZL) littermates, we compared the recovery period of hypersensitivity and therefore the progression of T2D and studied the possible involvement of insulin receptors (IR) within the comorbidity of those two conditions. We found that the nociceptive thresholds to thermal and mechanical stimulation in naïve ZDF rats were lower than in ZL littermates at 6 weeks of age. Although both ZDF and ZL rats developed thermal and tactile hypersensitivity after CCI, it took an extended time for the nociceptive sensitivity to revive in ZDF rats. Meanwhile, nerve injury accelerated the progression of T2D in ZDF rats, demonstrated by an earlier onset of hyperglycemia, more severe hyperinsulinemia, and a better concentration of glycosylated hemoglobin (HbAlc) six weeks after CCI, as compared to those in naïve ZDF and ZL rats. IR-immunoreactivity cells were located across the central nervous system 40; CNS41; and skeletal muscles. In the CNS, IR co-expressed with a neuronal marker (NeuN) but not a glial marker (GFAP).