Deficiency of Urokinase Plasminogen Activator May Impair β Cells Regeneration and Insulin Secretion in Type 2 Diabetes Mellitus
Abstract
:1. Introduction
2. Results and Discussion
2.1. uPA-/- Mice Were Prone to HyperGlycemia and Development of T2DM
2.2. uPA-/- Mice Failed to Regain Normal Insulin Secretion and Regeneration
2.3. After Treatment with uPA Plasmid, uPA-/- Mice Were Less Likely to Develop T2DM
2.4. The uPA Secretion Rate Decelerated and uPA Expression on β Cells Declined in High-Glucose Condition
2.5. Insulin Secretion Rate Decelerated and Replication of β Cell Declined in High Glucose after Silencing uPA
2.6. Treatment with uPA Enhanced β Cell Proliferation in Normal Glucose, but Insulin Secretion Rate Decelerated in High Glucose after Treatment with Anti-uPA Antibody
2.7. Better Insulin Secretion Capability after Oral Glucose Challenge in Patients with T2DM and Higher uPA Levels
2.8. Discussion
3. Materials and Methods
3.1. In Vivo Mice Study
3.1.1. Developmental of uPA-/- BALB/c Mice
Backcross Breeding
DNA from Tail Biopsy and Genotyping Identification
3.1.2. Induction of T2DM Mouse Model
3.1.3. uPA-/- Mice Treated with uPA Plasmid
3.1.4. Measurement of Murine uPA, Insulin, Glucagon, Insulin Resistance, and Secretion
3.1.5. Hematoxylin and Eosin (H&E) and IHC Stains of Islet for Insulin, Glucagon, uPA, and PCNA
3.2. In Vitro Cell Study
3.2.1. Assessing uPA Expression and Secretion of Murine β Cells in Normal or High Glucose Medium
3.2.2. Measurement of Insulin Secretion of β Cells with and without uPA Silencing
3.2.3. Measurement of β Cell Proliferation with and without uPA Silencing in High Glucose
3.2.4. Assessment of Insulin Secretion Rate and β Cell Proliferation after Treating with uPA
3.3. Clinical Investigation
3.3.1. Subjects
3.3.2. OGTT
3.3.3. Laboratory Measurement
3.4. Statistical Analysis
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Ethics Approval and Consent to Participate
Consent for Publication
Availability of Data and Material
Abbreviations
References
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Sample Availability: Samples are available from the first or corresponding author. |
uPA1 | uPA2 | uPA3 | uPA4 | All | |
---|---|---|---|---|---|
n | 28 | 28 | 28 | 28 | 112 |
uPA (pmol/L) | 6.1 ± 1.42,3,4 | 9.5 ± 0.81,3,4 | 12.9 ± 1.31,2,4 | 20.5 ± 4.91,2,3 | 12.2 ± 6.0 |
Sex (M/F) | 16/12 | 15/13 | 18/10 | 14/14 | 63/49 |
Age (year) | 52.6 ± 10.5 | 53.2 ± 9.9 | 52.6 ± 9.2 | 49.4 ± 11.6 | 51.9 ± 10.4 |
BMI (kg/m2) | 26.1 ± 4.3 | 26.7 ± 4.2 | 26.9 ± 3.8 | 27.2 ± 3.3 | 26.7 ± 3.9 |
HgbA1c (%) | 8.1 ± 1.22,4 | 7.2 ± 1.11,3 | 8.2 ± 1.82,4 | 6.9 ± 1.21,3 | 7.6 ± 1.4 |
FPG (mmol/L) | 8.6 ± 2.1 | 8.2 ± 2.4 | 9.6 ± 3.54 | 7.2 ± 3.23 | 8.4 ± 3.0 |
SBP (mmHg) | 122.8 ± 13.8 | 127.4 ± 13.8 | 125.7 ± 9.5 | 124.6 ± 1.6 | 125.1 ± 14.3 |
DBP (mmHg) | 74.4 ± 10.2 | 77.6 ± 12.0 | 78.4 ± 8.5 | 78.5 ± 10.5 | 77.2 ± 10.4 |
TG (mmol/L) | 1.60 ± 0.89 | 1.58 ± 0.91 | 1.95 ± 0.90 | 1.77 ± 1.12 | 1.72 ± 0.96 |
HDL (mmol/L) | 1.07 ± 0.33 | 1.16 ± 0.35 | 1.16 ± 0.62 | 1.05 ± 0.37 | 1.11 ± 0.42 |
LDL (mmol/L) | 2.59 ± 0.934 | 2.64 ± 0.654 | 2.79 ± 0.86 | 3.14 ± 0.891,2 | 2.79 ± 0.86 |
HOMA-β | 32.8 ± 43.8 | 56.6 ± 61.5 | 36.6 ± 42.7 | 108.3 ± 79.81,2,3 | 58.6 ± 65.5 |
HOMA-IR | 4.76 ± 3.23 | 6.56 ± 5.74 | 7.59 ± 5.73 | 6.30 ± 6.37 | 6.25 ± 5.42 |
FFA (μmol/L) | 83.4 ± 29.3 | 84.1 ± 29.1 | 89.6 ± 29.4 | 84.6 ± 24.5 | 85.4 ± 27.8 |
C-peptide (pmol/L) | 676.5 ± 337.2 | 643.6 ± 330.5 | 652.1 ± 322.8 | 826.8 ± 378.0 | 700.4 ± 346.5 |
Adiponectin | 7.70 ± 4.14 | 9.19 ± 7.78 | 8.28 ± 5.91 | 6.87 ± 3.63 | 8.01 ± 5.61 |
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Wu, C.-Z.; Ou, S.-H.; Chang, L.-C.; Lin, Y.-F.; Pei, D.; Chen, J.-S. Deficiency of Urokinase Plasminogen Activator May Impair β Cells Regeneration and Insulin Secretion in Type 2 Diabetes Mellitus. Molecules 2019, 24, 4208. https://doi.org/10.3390/molecules24234208
Wu C-Z, Ou S-H, Chang L-C, Lin Y-F, Pei D, Chen J-S. Deficiency of Urokinase Plasminogen Activator May Impair β Cells Regeneration and Insulin Secretion in Type 2 Diabetes Mellitus. Molecules. 2019; 24(23):4208. https://doi.org/10.3390/molecules24234208
Chicago/Turabian StyleWu, Chung-Ze, Shih-Hsiang Ou, Li-Chien Chang, Yuh-Feng Lin, Dee Pei, and Jin-Shuen Chen. 2019. "Deficiency of Urokinase Plasminogen Activator May Impair β Cells Regeneration and Insulin Secretion in Type 2 Diabetes Mellitus" Molecules 24, no. 23: 4208. https://doi.org/10.3390/molecules24234208
APA StyleWu, C. -Z., Ou, S. -H., Chang, L. -C., Lin, Y. -F., Pei, D., & Chen, J. -S. (2019). Deficiency of Urokinase Plasminogen Activator May Impair β Cells Regeneration and Insulin Secretion in Type 2 Diabetes Mellitus. Molecules, 24(23), 4208. https://doi.org/10.3390/molecules24234208