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Insulin receptor in rat peripheral nerve: its localization and alternatively spliced isoforms
K Sugimoto1, Y Murakawa, W Zhang
1Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Diabetes/Metabolism Research and Reviews
|October 12, 2000
Summary
Diabetic neuropathy involves insulin receptor (IR) differences in Type 1 and Type 2 diabetes. This study found IR in rat peripheral nerves, crucial for nerve barriers.
Area of Science:
- Neuroscience
- Endocrinology
- Cell Biology
Background:
- Diabetic neuropathy presents differently in Type 1 and Type 2 diabetes.
- Type 1 diabetic neuropathy shows severe functional deficits linked to paranodal degeneration.
- Insulin deficiency, not just hyperglycemia, may drive neuropathy pathogenesis.
Purpose of the Study:
- Investigate insulin receptor (IR) localization in adult rat peripheral nerve.
- Determine the expression of the two IR isoforms in peripheral nerve.
Main Methods:
- Utilized light and ultrastructural immunohistochemistry for IR localization.
- Employed reverse transcription polymerase chain reaction (RT-PCR) to identify IR isoforms.
- Assessed mRNA localization using in situ hybridization.
Main Results:
- IR localized to Schwann cell loops, axolemma, and Schmidt-Lanterman incisures.
- Endoneurial vessels showed IR on endothelial cells and pericytes, near tight junctions.
- Peripheral nerve predominantly expresses the high-affinity IR isoform (lacking exon 11), with mRNA in Schwann cells, endothelial cells, and pericytes.
Conclusions:
- Peripheral nerve primarily expresses the high-affinity IR.
- IR is strategically located at the blood-nerve and paranodal ion-channel barriers.
- These findings suggest IR's role in maintaining nerve integrity in diabetes.