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Diagnostic potential of miR-483 family for IGF-II producing non-islet cell tumor hypoglycemia
Mototsugu Nagao1,2, Izumi Fukuda1, Akira Asai1
1Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
Objective:
In insulin-like growth factor II (IGF-II) producing non-islet cell tumor hypoglycemia (NICTH), high molecular weight forms of IGF-II (big IGF-II) are produced as a cause of spontaneous hypoglycemia. MicroRNA (miRNA)-483 family, encoded in an intron lesion of IGF2 gene, is suggested to be co-expressed with IGF-II. Here, we tested whether serum miR-483-5p and -3p levels are associated with the presence of big IGF-II in NICTH.
Design:
Serum samples from patients who were suspected to have IGF-II producing NICTH (n = 42) were tested. MiR-483-5p and -3p levels were evaluated using quantitative PCR. IGF-II level was analyzed using ELISA. The presence of big IGF-II was identified by Western blotting.
Results:
Big IGF-II was detected in the sera of 32 patients. MiR-483-5p (P = 0.0015) and -3p (P = 0.027) levels were significantly higher in sera with big IGF-II (n = 32) than in those without (n = 10), whereas serum IGF-II level (P = 0.055) was not significantly different between the groups. The median serum concentration of miR-483-5p was ~10 times higher than that of miR-483-3p. Although a strong correlation was observed between the two miRNAs (r = 0.844, P < 0.0001), but neither of which was correlated with serum IGF-II level. The areas under the receiver operating characteristic curves of miR-483-5p (0.853) and -3p (0.722) were higher than that of IGF-II (0.694) for detecting the presence of big IGF-II.
Conclusion:
The associations of serum miR-483-5p and -3p levels with the presence of big IGF-II suggest the diagnostic potential of these miRNAs for IGF-II producing NICTH.
Insights
Serum miR-483-5p and -3p levels are elevated in patients with insulin-like growth factor II (IGF-II) producing non-islet cell tumor hypoglycemia (NICTH) and the presence of big IGF-II. These microRNAs show diagnostic potential for this condition.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Non-islet cell tumor hypoglycemia (NICTH) is often caused by insulin-like growth factor II (IGF-II) producing tumors.
- High molecular weight forms of IGF-II (big IGF-II) are implicated in NICTH pathogenesis.
- MicroRNA (miRNA)-483, encoded within the IGF2 gene, is potentially co-expressed with IGF-II.
Purpose of the Study:
- To investigate the association between serum levels of miR-483-5p and miR-483-3p and the presence of big IGF-II in patients with suspected IGF-II producing NICTH.
- To evaluate the diagnostic utility of these miRNAs for identifying big IGF-II in NICTH.
Main Methods:
- Serum samples from 42 patients with suspected IGF-II producing NICTH were analyzed.
- Quantitative PCR was used to measure miR-483-5p and -3p levels.
- ELISA measured total IGF-II, and Western blotting identified the presence of big IGF-II.
Main Results:
- Big IGF-II was detected in 32 patients.
- Serum miR-483-5p and -3p levels were significantly higher in patients with big IGF-II compared to those without.
- Neither miRNA level correlated with total serum IGF-II, but their diagnostic performance for big IGF-II exceeded that of total IGF-II.
Conclusions:
- Elevated serum miR-483-5p and -3p levels are associated with the presence of big IGF-II in NICTH.
- These miRNAs demonstrate potential as biomarkers for diagnosing IGF-II producing NICTH.
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