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Effect of glycemic control on corneal nerves and peripheral neuropathy in streptozotocin-induced diabetic C57Bl/6J mice
Journal article   Peer reviewed

Effect of glycemic control on corneal nerves and peripheral neuropathy in streptozotocin-induced diabetic C57Bl/6J mice

Matthew S Yorek, Alexander Obrosov, Hanna Shevalye, Sergey Lupachyk, Matthew M Harper, Randy H Kardon and Mark A Yorek
Journal of the peripheral nervous system, Vol.19(3), pp.205-217
09/2014
DOI: 10.1111/jns.12086
PMCID: PMC4986703
PMID: 25403729

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Abstract

We sought to determine the impact that duration of hyperglycemia and control has on corneal nerve fiber density in relation to standard diabetic neuropathy endpoints. Control and streptozotocin-diabetic C57Bl/6J mice were analyzed after 4, 8, 12, and 20 weeks. For the 20-week time point, five groups of mice were compared: control, untreated diabetic, and diabetic treated with insulin designated as having either poor glycemic control, good glycemic control, or poor glycemic control switched to good glycemic control. Hyperglycemia was regulated by use of insulin-releasing pellets. Loss of corneal nerves in the sub-epithelial nerve plexus or corneal epithelium progressed slowly in diabetic mice requiring 20 weeks to reach statistical significance. In comparison, slowing of motor and sensory nerve conduction velocity developed rapidly with significant difference compared with control mice observed after 4 and 8 weeks of hyperglycemia, respectively. In diabetic mice with good glycemic control, average blood glucose levels over the 20-week experimental period were lowered from 589 ± 2 to 251 ± 9 mg/dl. All diabetic neuropathy endpoints examined were improved in diabetic mice with good glycemic control compared with untreated diabetic mice. However, good control of blood glucose was not totally sufficient in preventing diabetic neuropathy.
Insulin - pharmacology Diabetes Mellitus, Experimental - drug therapy Diabetic Neuropathies - etiology Mice, Inbred C57BL Hyperglycemia - complications Hyperglycemia - drug therapy Hypoglycemic Agents - pharmacology Animals Hyperglycemia - chemically induced Nerve Fibers - physiology Cornea - innervation Diabetes Mellitus, Experimental - chemically induced Diabetes Mellitus, Experimental - complications Epithelium, Corneal - innervation Mice Streptozocin - toxicity Anti-Bacterial Agents - toxicity Diabetic Neuropathies - physiopathology

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