Info

BBZDR/Wor-rats

Ennia

BB/Wor-rats + C-peptide

1 week 2 month 4 month 6 month 8 month Duration of diabetes

Fig. 4. Latencies of hind paw withdrawal after a noxious thermal stimulus reflecting C-fiber function. In type 1 BB/Wor-rats the latencies decreased significantly to less than half of that in control rats. Hyperalgesia reflects hyperexcitability of damaged C-fibers (see text). This decrease was followed by a recovery of the latencies most likely reflecting loss of hyperexcitable C-fibers (see Fig. 6). In the type 2 BBZDR/Wor-rat the decrease in latency to thermal stimuli was slower and was only significantly different from that in control rats after 6 months of diabetes consistent with the near normal morphometric parameters of C-fibers in this model (Fig. 6). C-peptide replacement in BB/Wor-rat significantly prevented hyperalgesia resulting in a profile similar to that in BBZDR/Wor-rat. The data points represent the means ± SD's of at least eight animals.

1 week 2 month 4 month 6 month 8 month Duration of diabetes

Fig. 4. Latencies of hind paw withdrawal after a noxious thermal stimulus reflecting C-fiber function. In type 1 BB/Wor-rats the latencies decreased significantly to less than half of that in control rats. Hyperalgesia reflects hyperexcitability of damaged C-fibers (see text). This decrease was followed by a recovery of the latencies most likely reflecting loss of hyperexcitable C-fibers (see Fig. 6). In the type 2 BBZDR/Wor-rat the decrease in latency to thermal stimuli was slower and was only significantly different from that in control rats after 6 months of diabetes consistent with the near normal morphometric parameters of C-fibers in this model (Fig. 6). C-peptide replacement in BB/Wor-rat significantly prevented hyperalgesia resulting in a profile similar to that in BBZDR/Wor-rat. The data points represent the means ± SD's of at least eight animals.

period (Fig. 4). However, in type 1 BB/Wor-rats, there is a rapid and progressive decline in the latencies during the first 6 months of diabetes, followed by an increase from 6 to 10 months of diabetes, representing increasing relative analgesia (47). The hyperalgesia in type 1 BB/Wor-rats can be significantly, but not completely prevented by insulinomimetic C-peptide (Fig. 4) (47). In contrast the type 2 BBZDR/Wor-rat shows a significantly slower progression of hyperalgesia (Fig. 4) (46).

Nociceptive C-fibers emanate from small nociceptive SP and CGRP dorsal root ganglion cells, which are dependent on neurotrophic support by NGF, insulin, and IGF-1 (10,44,70). In the BB/Wor-rat both systemic insulin and IGF-1 are significantly diminished as is endogenous IGF-1, abnormalities which are coupled with significantly decreased expression of the insulin and IGF-1 receptors in dorsal root ganglia (46). These changes are either milder or nonexistent even in chronically diabetic BBZDR/Wor-rat (46). Added to these deficiencies, sciatic nerve NGF as well as the expression of NGF-TrkA in dorsal root ganglion cells are more severely affected in the type 1 model (46). Hence, as would be expected, these deficiencies lead to impaired expression of SP and CGRP in type 1 but not in type 2 BB-rats (46). The underlying molecular abnormalities in the type 1 BB/Wor-rat are almost totally prevented by replenishment of insulinomimetic C-peptide that is associated with prevention of hyperalgesia (47,71), which suggests that nociceptive sensory neuropathy is mainly an insulin/C-peptide deficiency-mediated phenomenon rather than a hyperglycemia-induced entity. This is further supported by the frequent occurrence of "idiopathic" painful neuropathy in patients (72,73) and animals (70) with prediabetes or impaired glucose tolerance and P-cell dysfunction.

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

Get My Free Ebook


Post a comment