Hypoglycaemic neuropathy: occurrence of axon terminals in plantar skin and plantar muscle of diabetic BB/Wor rats treated with insulin implants

Abstract

It is generally believed that diabetic neuropathy is due to chronic hyperglycaemia. However, experience from insulinoma patients and experimental studies show that hypoglycaemia may also cause neuropathy. Accordingly, the plantar nerves of diabetic eu-/hypoglycaemic BB/Wor rats treated with insulin implants exhibit a distinct neuropathy. To what extent hypoglycaemic neuropathy affects axon terminals in skin and muscle is unknown. In the present study we examine the occurrence of epidermal axon profiles and the neuropeptide calcitonin gene-related peptide (CGRP) in plantar skin, and of end plate axon terminals in a plantar muscle of diabetic BB/Wor rats subjected to long periods of hypoglycaemia. The number of protein gene product-immunoreactive axon profiles was found to be normal in heel skin biopsy specimens from eu-/hypoglycaemic rats, but many profiles were short and thin. The content of CGRP in the skin biopsy samples was significantly below normal. After staining with antibodies against the vesicular acetylcholine transporter protein, the occurrence of end plate axon terminals was significantly reduced in sections from the flexor hallucis brevis muscle of eu-/hypoglycaemic rats. Moreover, the end plate axon terminals tended to be abnormally small in these rats. We conclude that the hypoglycaemic neuropathy seen in plantar nerve trunks of diabetic BB/Wor rats treated with insulin implants is accompanied by mild alterations in the epidermal innervation of plantar skin and a more obviously abnormal nerve terminal pattern in plantar muscle.

Effect of Insulin‐Induced Hypoglycaemia on the Peripheral Nervous System: Focus on Adaptive Mechanisms, Pathogenesis and Histopathological Changes

“…This is further supported by several studies in diabetic rats with chronic recurrent IIH. IIH had a more severe impact on motor nerve terminals in hind paw muscle than on the sensory nerve endings in hind paw skin in one study , in agreement with a later study by the same group showing a more severe impact on somatic motor fibres than on somatic sensory fibres in the vagus nerve . Thus, rather convincing evidence exists indicating that it is a sensory‐motor neuropathy affecting motor fibres more severely than sensory fibres.…”

Discordant Trends in Microvascular Complications in Adolescents With Type 1 Diabetes From 1990 to 2002

“…Increasing height was associated with peripheral neuropathy in the EURODIAB IDDM Complications Study (34) and clinical neuropathy in the DCCT baseline study (35). A unifying hypothesis for our discordant finding of an increase in peripheral nerve abnormalities with a reduction in early renal and retinal disease would be an increased rate of hypoglycemia, because the cerebral and peripheral nervous systems are adversely affected by hypoglycemia (36), whereas the blood vessels of the retina and nephron are not. Although patient recall of hypoglycemia did not change over time, milder hypoglycemia may have contributed to our findings.…”

Extended longevity mechanisms in short-lived progeroid mice: Identification of a preservative stress response associated with successful aging

“…The loss of Purkinje neurons typical of progeroid NER mice may be due to a celltype specific hypersensitivity to oxidative DNA damage combined with the systemic effects of reduced IGF-1, a neuronal survival factor. Decreased serum IGF-1 levels are associated with cerebellar ataxias of various etiologies in both humans and experimental rodent models (Busiguina et al, 2000;Torres-Aleman et al, 1996), and Purkinje neurons are hypersensitive to oxidative stress accompanying ischemic injury although relatively resistant to other types of stress such as hypoglycemia (Mohseni, 2001). Interestingly, different gene-specific pathologies also exist amongst progeroid NER disorders (Table 1).…”