Successful sulfonylurea treatment in a patient with permanent neonatal diabetes mellitus with a novel KCNJ11 mutation / 소아과

Permanent neonatal diabetes mellitus refers to diabetes that occurs before the age of 6 months and persists through life. It is a rare disorder affecting one in 0.2-0.5 million live births. Mutations in the gene KCNJ11, encoding the subunit Kir6.2, and ABCC8, encoding SUR1 of the ATP-sensitive potassium (K(ATP)) channel, are the most common causes of permanent neonatal diabetes mellitus. Sulfonylureas close the K(ATP) channel and increase insulin secretion. KCNJ11 and ABCC8 mutations have important therapeutic implications because sulfonylurea therapy can be effective in treating patients with mutations in the potassium channel subunits. The mutation type, the presence of neurological features, and the duration of diabetes are known to be the major factors affecting the treatment outcome after switching to sulfonylurea therapy. More than 30 mutations in the KCNJ11 gene have been identified. Here, we present our experience with a patient carrying a novel p.H186D heterozygous mutation in the KCNJ11 gene who was successfully treated with oral sulfonylurea.

Diabetes mellitus neonatal en Costa Rica / Neonatal diabetes mellitus in Costa Rica

La diabetes mellitus neonatal es un raro desorden metabólico usualmente desarrollado en las primeas 6 semanas de vida, secundario a un grupo de mutaciones y defectos del desarrollo pancreático que puede desembocar en una catástrofe clínica si no se identifica tempranamente; se divide en una variante transitoria y una permanente, siendo la primera la más frecuente, con cerca de un 60 por ciento de los casos. El manejo inicial de ambas variantes es la insulinoterapia intensiva, que en la variante transitoria puede suspenderse usualmente en los primeros meses de vida...

Study of Mechanism of Proinsulin Gene Mutations in Diabetes Mellitus / 天津医药

Objective To construct several human proinsulin mutants plasmid related to diabetes and to express in INS-1 (Insulin secreting beta cell derived line) cell. Methods Human mild proinsulin gene was used as template , and site-directed mutagenesis PCR was employed to generate four human proinsulin plasmid mutants. Each mutant plasmid was sequenced then transfected with empty plasmid and mild plasmid into INS-1 cell by liposome 2000. Insulin value in each cell solution was determined by radioimmunoassay. Results Proinsulin mutants plasmid were confirmed by sequencing. In-sulin values in culture solution of H-C(B19)G、H-L(B11)P、H-R(S6)C mutants are less than those in wild type and H-F (B25)L(P＜0.05). Comparison of insulin values between H-C(B19)G、H-L(B11)P、H-R(S6)C groups were not statistically significant(P>0.05), and all these three groups showed no significant differences with empty plasmid group statistically (P>0.05).Insulin value of H-F(B25)L was of no significant differences statistically with empty plasmid(P>0.05). Conclu-sion Four human proinsulin mutants plasmid were constructed and expressed successfully in INS-1 cell, and different mu-tants plasmid result in diabetes through different mechanism.