Human islets expressing HNF1A variant have defective ß cell transcriptional regulatory networks.
J Clin Invest
; 129(1): 246-251, 2019 01 02.
Article
en En
| MEDLINE
| ID: mdl-30507613
ABSTRACT
Using an integrated approach to characterize the pancreatic tissue and isolated islets from a 33-year-old with 17 years of type 1 diabetes (T1D), we found that donor islets contained ß cells without insulitis and lacked glucose-stimulated insulin secretion despite a normal insulin response to cAMP-evoked stimulation. With these unexpected findings for T1D, we sequenced the donor DNA and found a pathogenic heterozygous variant in the gene encoding hepatocyte nuclear factor-1α (HNF1A). In one of the first studies of human pancreatic islets with a disease-causing HNF1A variant associated with the most common form of monogenic diabetes, we found that HNF1A dysfunction leads to insulin-insufficient diabetes reminiscent of T1D by impacting the regulatory processes critical for glucose-stimulated insulin secretion and suggest a rationale for a therapeutic alternative to current treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transcripción Genética
/
Variación Genética
/
Diabetes Mellitus Tipo 1
/
Células Secretoras de Insulina
/
Factor Nuclear 1-alfa del Hepatocito
Límite:
Adolescent
/
Adult
/
Humans
/
Male
Idioma:
En
Revista:
J Clin Invest
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos