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Isolation of Human Islets from Partially Pancreatectomized Patients
Published on: July 30, 2011
Circulating miRNA in Patients Undergoing Total Pancreatectomy and Islet Autotransplantation
Srividya Vasu1, Jiemin M Yang2, James Hodges2
1Islet Cell Laboratory, Baylor University Medical Center, Dallas TX, USA.
Abstract:
Circulating microRNAs (miRNAs) can be biomarkers for diagnosis and progression of several pathophysiological conditions. In a cohort undergoing total pancreatectomy with islet autotransplantation (TPIAT) from the multicenter Prospective Observational Study of TPIAT (POST), we investigated associations between a panel of circulating miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-320d, hsa-miR-200c, hsa-miR-125b, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-122-5p) and patient, disease and islet-isolation characteristics. Plasma samples (n = 139) were collected before TPIAT and miRNA levels were measured by RTPCR. Disease duration, prior surgery, and pre-surgical diabetes were not associated with circulating miRNAs. Levels of hsa-miR-29b-3p (P = 0.03), hsa-miR-148a-3p (P = 0.04) and hsa-miR-221-3p (P = 0.01) were lower in those with genetic risk factors. Levels of hsa-miR-148a-3p (P = 0.04) and hsa-miR-7-5p (P = 0.04) were elevated in toxic/metabolic disease. Participants with exocrine insufficiency had lower hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-320d, hsa-miR-221-3p (P < 0.01) and hsa-miR-375, hsa-miR-200c-3p, and hsa-miR-125b-5p (P < 0.05). Four miRNAs were associated with fasting C-peptide before TPIAT (hsa-miR-29b-3p, r = 0.18; hsa-miR-148a-3p, r = 0.21; hsa-miR-320d, r = 0.19; and hsa-miR-221-3p, r = 0.21; all P < 0.05), while hsa-miR-29b-3p was inversely associated with post-isolation islet equivalents/kg and islet number/kg (r = -0.20, P = 0.02). Also, hsa-miR-200c (r = 0.18, P = 0.03) and hsa-miR-221-3p (r = 0.19, P = 0.03) were associated with islet graft tissue volume. Further investigation is needed to determine the predictive potential of these miRNAs for assessing islet autotransplant outcomes.
Insights
Circulating microRNAs (miRNAs) show potential as biomarkers in total pancreatectomy with islet autotransplantation (TPIAT). Specific miRNAs correlate with genetic risk, disease type, exocrine insufficiency, and islet yield, suggesting their role in TPIAT outcomes.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Circulating microRNAs (miRNAs) are increasingly recognized as valuable biomarkers for diagnosing and monitoring various pathophysiological conditions.
- Total pancreatectomy with islet autotransplantation (TPIAT) is a complex procedure for managing pancreatic diseases, and identifying reliable biomarkers for patient stratification and outcome prediction is crucial.
Purpose of the Study:
- To investigate the associations between a panel of circulating miRNAs and patient, disease, and islet-isolation characteristics in a cohort undergoing TPIAT.
- To explore the potential of circulating miRNAs as predictive biomarkers for TPIAT outcomes.
Main Methods:
- A cohort of 139 patients undergoing TPIAT was studied, with plasma samples collected pre-procedure.
- Levels of ten specific circulating miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-320d, hsa-miR-200c, hsa-miR-125b, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-122-5p) were measured using RT-PCR.
- Statistical analyses were performed to assess correlations between miRNA levels and clinical/biological parameters.
Main Results:
- Circulating miRNA levels were not associated with disease duration, prior surgery, or pre-surgical diabetes.
- Lower levels of hsa-miR-29b-3p, hsa-miR-148a-3p, and hsa-miR-221-3p were observed in individuals with genetic risk factors.
- Elevated levels of hsa-miR-148a-3p and hsa-miR-7-5p were found in patients with toxic/metabolic disease.
- Participants with exocrine insufficiency exhibited lower levels of several miRNAs, including hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-320d, and hsa-miR-221-3p.
- Four miRNAs (hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-320d, hsa-miR-221-3p) were associated with pre-TPIAT fasting C-peptide levels.
- hsa-miR-29b-3p showed an inverse association with post-isolation islet equivalents and number per kilogram.
- hsa-miR-200c and hsa-miR-221-3p were associated with islet graft tissue volume.
Conclusions:
- Specific circulating miRNAs are associated with genetic risk factors, disease etiology, exocrine insufficiency, and islet yield in patients undergoing TPIAT.
- These findings suggest that circulating miRNAs may serve as potential biomarkers for predicting TPIAT outcomes.
- Further research is warranted to validate the predictive utility of these miRNAs in larger cohorts and diverse clinical settings.

