Estimated proinsulin processing activity of prohormone convertase (PC) 1/3 rather than PC2 is decreased in pancreatic ß-cells of type 2 diabetic patients.
Endocr J
; 61(6): 607-14, 2014.
Article
em En
| MEDLINE
| ID: mdl-24705588
ABSTRACT
Type 2 diabetic (T2D) patients exhibit fasting relative hyperproinsulinemia owing to pancreatic ß-cell dysfunction. To clarify the mechanism underlying this hyperproinsulinemic state, we evaluated the activities of the endopeptidases prohormone convertase (PC) 1/3 and PC2 in T2D patients. Fasting blood levels of intact proinsulin (IPI), total proinsulin (t-PI) and C-peptide were measured simultaneously, and intravenous glucagon loading was performed to investigate the dynamics of circulating proinsulin-related molecules released from pancreatic ß-cells in 12 healthy volunteers and 18 T2D patients. Taking advantage of the 95% cross-reactivity between proinsulin and des-31,32-proinsulin (des-31,32-PI) with the human proinsulin radioimmunoassay kit used in this study, we estimated PC1/3 and PC2 activities using the following formulas des-31,32-PI = (t-PI-IPI)/0.95; PC1/3 activity = des-31,32-PI/IPI; and PC2 activity = C-peptide/des-31,32-PI. C-peptide responses to glucagon were slightly lower among T2D patients. IPI and the IPI/C-peptide ratio were significantly higher in T2D patients (p<0.05 and p<0.01, respectively). There was no difference in des-31,32-PI levels or PC2 activity between the two groups. However, PC1/3 activity was significantly lower in T2D patients than in the control group (p<0.01). We propose that decreased activity of PC1/3 rather than PC2 in pancreatic ß-cells is involved in the impaired proinsulin processing, resulting in elevated IPI levels in T2D patients.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Proinsulina
/
Processamento de Proteína Pós-Traducional
/
Pró-Proteína Convertase 1
/
Pró-Proteína Convertase 2
/
Diabetes Mellitus Tipo 2
/
Células Secretoras de Insulina
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article