OBJECTIVE: To explore the relation between carboxypeptidase-H antibody (CPH-Ab) and islet beta cell function in patients with latent autoimmune diabetes in adults (LADA) and to further confirm the diagnostic value of CPH-Ab for LADA. METHODS: Five hundred and forty-five patients who were initially diagnosed as Type 2 diabetes mellitus (T2DM) were tested with CPH-Ab and GAD-Ab by radioligand assay (RLA). T2DM patients, according to CPH-Ab and GAD-Ab status, were divided into CPH-Ab(+) group, GAD-Ab(+) group, and Ab(-) group to compare their islet beta cell function [represented by fasting C-peptide (FCP) and 2h postprandial C-peptide (2hCP)]. The relation between CPH-Ab and islet beta cell function in LADA was analyzed. RESULTS: The fasting C-peptide level in CPH-Ab(+) patients was between that of GAD-Ab(+) patients and that of Ab(-) patients (P<0.05), and the difference was still significant when the 3 groups were stratified with duration of disease (All P<0.05), but not with body mess index (all P>0.05). Corrected by concomitant variables including age, age at onset, duration of disease, and sex, the differences among the 3 groups were statistically significant (both P<0.001). Among the 3 groups FCP was lower than Ab(-) group in CPH-Ab(+) (P<0.05) and both FCP and PCP were lower than Ab(-) group in GAD-Ab(+) group (P<0.05 and P<0.01). The proportions of patients with insulin deficiency in CPH-Ab(+), GAD-Ab(+), and Ab(-) group were 27.6% (8/29), 48.1% (8/52) and 13.5% (54/400), respectively, which were significantly different among the 3 groups (P<0.001). GAD-Ab, BMI, and fasting blood glucose had effects on FCP and PCP in T2DM patients (All P<0.05), while CPH-Ab did not enter the equation in multivariable stepwise regressive analysis (P>0.05). CONCLUSION The effect of CPH-Ab is less marked than that of GAD-Ab on islet beta-cell function in LADA patients. The value of CPH-Ab for the failure of islet beta-cell function in LADA should be determined prospectively.
Adult ; Aged ; Aged, 80 and over ; Autoantibodies ; blood ; Carboxypeptidase H ; immunology ; Cross-Sectional Studies ; Diabetes Mellitus, Type 1 ; blood ; diagnosis ; immunology ; Female ; Humans ; Insulin-Secreting Cells ; physiology ; Male ; Middle Aged

OBJECTIVETo observe the change of the neuropeptide pro-protein processing system in the ischemic retina ganglion cell-5 (RGC-5) cells, pro-protein convertase-2 (PC2), carboxypeptidase-E (CPE) and preproneuropeptide Y (preproNPY) protein levels in the ischemic RGC-5 cells and conditioned medium were analyzed.

METHODSThe RGC-5 cell was differentiated in 0.1 mumol/L staurosporine for 24 h and then stressed by different doses of oxygen and glucose deprivation (OGD). The acute or chronic OGD-induced cell death rates were obtained by using PI or TUNEL staining. The protein expression levels were determined by using the Western blot method and PC2 activity analysis.

RESULTSThe ischemia caused substantial cell death in an OGD dose-dependent manner. In the cells, proPC2 and preproNPY protein levels gradually increased whereas proCPE gradually decreased. After OGD, PC2 activity was decreased. In the conditioned medium, proPC2 and PC2 proteins gradually decreased whereas proCPE, CPE, and preproNPY proteins gradually increased.

CONCLUSIONThese results demonstrated that OGD inhibited the neuropeptide pro-protein processing system by reducing PC2 activity and the maturation of proPC2. The aggregation of the pro-proteins and the increase of the active CPE excision adversely exacerbated the cell injury. The pro-protein processing system might play a critical role in the ischemic stress of RGC-5 cells.

Animals ; Carboxypeptidase H ; metabolism ; Cell Death ; drug effects ; physiology ; Cell Differentiation ; drug effects ; Cell Hypoxia ; drug effects ; physiology ; Cell Line, Transformed ; Enzyme Inhibitors ; pharmacology ; Gene Expression Regulation, Enzymologic ; drug effects ; physiology ; Glucose ; deficiency ; In Situ Nick-End Labeling ; methods ; Indoles ; Neuropeptide Y ; metabolism ; Proprotein Convertase 2 ; metabolism ; Protein Precursors ; metabolism ; Rats ; Retinal Ganglion Cells ; drug effects ; metabolism ; Staurosporine ; pharmacology ; Time Factors