Erythropoietin both protects from and reverses experimental diabetic neuropathy

Abstract

Tail-nerve conduction velocities (NCV) was assessed at 5 and 11 weeks for the preventive and therapeutic schedule, respectively. Compared to nondiabetic rats, NCV was 20% lower after 5 weeks in the STZ group, and this decrease was attenuated 50% by rhEPO. Furthermore, the reduction of Na ؉ ,K ؉ -ATPase activity of diabetic nerves (by 55%) was limited to 24% in the rhEPO-treated group. In the therapeutic schedule, NCV was reduced by 50% after 11 weeks but by only 23% in the rhEPO-treated group. rhEPO treatment attenuated the decrease in compound muscle action potential in diabetic rats. In addition, rhEPO treatment was associated with a preservation of footpad cutaneous innervation, as assessed by protein gene product 9.5 immunostaining. Diabetic rats developed alterations in mechanical and thermal nociception, which were partially reversed by rhEPO given either in a preventative or therapeutic manner. These observations suggest that administration of rhEPO or its analogues may be useful in the treatment of diabetic neuropathy.

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

“…2), indicates that there is a significant decrease in both IENFD as compared to non-diabetic controls. These data results for IENFD in controls and diabetics are similar to previously published reports in rats and humans (Bianchi et al, 2004;Hirai et al, 2000;Leonelli et al, 2007).…”

“…The timing of increases in TGF-β mRNA and protein show an association with decreased nerve conduction velocities, paw withdrawal threshold, IENFD and fiber length in the STZ diabetic model. IENFD is a good marker of early neuropathy both in rodents and humans (Bianchi et al, 2004;Hirai et al, 2000;Leonelli et al, 2007;Polydefkis et al, 2004). Other models of nerve injury, for example sciatic cryoneurolysis and chronic constriction injury, show a similar increase in cytokine production including TGF-β in the spinal cord and dorsal and ventral roots Willenbring et al, 1994).…”

Anaemia in diabetes: is there a rationale to TREAT?

“…Treatment with erythropoietin in diabetic patients with heart failure may also reduce the length of hospitalisation and improve New York Heart Association functional class [42]. In experimental models of diabetes, treatment with erythropoietin has been shown to protect against the development of diabetic neuropathy as well as to reverse established disease [43]. However, it remains to be established whether these actions are the In patients with type 2 diabetes and overt nephropathy, the haemoglobin level is associated with a shorter time to doubling of serum creatinine or ESRD, after adjusting for baseline systolic blood pressure, albuminuria and glycaemic control (adapted from [8]); **p<0.01 vs patients with Hb 140-160 result of correction of the anaemia, or of the pleiotropic actions of erythropoietin on the physiological response to hypoxia and oxidative stress [44].…”

Regression of diabetic complications by islet transplantation in the rat

“…Decreased NCV, together with reductions in Na + , K + -ATPase activity, is the hallmark of diabetic neuropathy, but these rats present various types of early neurological dysfunction [14], including altered pain sensation suggesting early involvement of small nociceptive sensory neurons [15]. Alterations in nociceptive threshold can be partially prevented and restored by erythropoietin, prosaposin-derived peptide and neuroactive steroids [14,16,17]. Hyperglycaemia plays a major role in the onset and progression of long-term diabetic complications, although insulin deficiency itself may also contribute [18].…”