Diabetes & Metabolism Journal

Original Article

Complications
Influence of Glucose Fluctuation on Peripheral Nerve Damage in Streptozotocin-Induced Diabetic Rats: Yu Ji Kim, Na Young Lee, Kyung Ae Lee, Tae Sun Park, Heung Yong Jin; Diabetes Metab J. 2022;46(1):117-128. Published online September 9, 2021; DOI: https://doi.org/10.4093/dmj.2020.0275

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Background
It is unclear whether glycemic variability (GV) is a risk factor for diabetic peripheral neuropathy (DPN), and whether control of GV is beneficial for DPN. The purpose of this study was to investigate the effect of GV on peripheral nerve damage by inducing glucose fluctuation in streptozotocin-induced diabetic rats.
Methods
Rats were divided into four groups: normal (normal glucose group [NOR]), diabetes without treatment (sustained severe hyperglycemia group; diabetes mellitus [DM]), diabetes+once daily insulin glargine (stable hyperglycemia group; DM+LAN), and diabetes+once daily insulin glargine with twice daily insulin glulisine (unstable glucose fluctuation group; DM+Lantus [LAN]+Apidra [API]). We measured anti-oxidant enzyme levels and behavioral responses against tactile, thermal, and pressure stimuli in the plasma of rats. We also performed a quantitative comparison of cutaneous and sciatic nerves according to glucose fluctuation.
Results
At week 24, intraepidermal nerve fiber density was less reduced in the insulin-administered groups compared to the DM group (P<0.05); however, a significant difference was not observed between the DM+LAN and DM+LAN+API groups irrespective of glucose fluctuation (P>0.05; 16.2±1.6, 12.4±2.0, 14.3±0.9, and 13.9±0.6 for NOR, DM, DM+LAN, and DM+LAN+API, respectively). The DM group exhibited significantly decreased glutathione levels compared to the insulin-administered groups (2.64±0.10 μmol/mL, DM+LAN; 1.93±0.0 μmol/mL, DM+LAN+API vs. 1.25±0.04 μmol/mL, DM; P<0.05).
Conclusion
Our study suggests that glucose control itself is more important than glucose fluctuation in the prevention of peripheral nerve damage, and intra-day glucose fluctuation has a limited effect on the progression of peripheral neuropathy in rats with diabetes.

Citations

Citations to this article as recorded by

Glucose Fluctuation Inhibits Nrf2 Signaling Pathway in Hippocampal Tissues and Exacerbates Cognitive Impairment in Streptozotocin-Induced Diabetic Rats
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Journal of Diabetes Research.2024; 2024: 1. CrossRef
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Biological and Pharmaceutical Bulletin.2023; 46(6): 764. CrossRef
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Brief Report

Complications
Effect of Empagliflozin, a Selective Sodium-Glucose Cotransporter 2 Inhibitor, on Kidney and Peripheral Nerves in Streptozotocin-Induced Diabetic Rats: Kyung Ae Lee, Heung Yong Jin, Na Young Lee, Yu Ji Kim, Tae Sun Park; Diabetes Metab J. 2018;42(4):338-342. Published online April 25, 2018; DOI: https://doi.org/10.4093/dmj.2017.0095

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77 Download
18 Web of Science
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Abstract PDF PubReader

The effect of sodium-glucose cotransporter 2 inhibitors on peripheral nerves and kidneys in diabetes mellitus (DM) remains unexplored. Therefore, this study aimed to explore the effect of empagliflozin in diabetic rats. DM in rats was induced by streptozotocin injection, and diabetic rats were treated with empagliflozin 3 or 10 mg/kg. Following 24-week treatment, response thresholds to four different stimuli were tested and found to be lower in diabetic rats than in normal rats. Empagliflozin significantly prevented hypersensitivity (P<0.05) and the loss of skin intraepidermal nerve fibers, and mesangial matrix expansion in diabetic rats. Results of this study demonstrate the potential therapeutic effects of empagliflozin for the treatment of diabetic peripheral neuropathy and nephropathy.

Citations

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