Lack of the architectural factor HMGA1 causes insulin resistance and diabetes in humans and mice(491 views) Foti D, Chiefari E, Fedele M, Iuliano R, Brunetti L, Paonessa F, Manfioletti G, Barbetti F, Brunetti A, Croce CM, Fusco A, Brunetti A
Nat Med (ISSN: 1078-8956, 0034-7264), 2005 Jul; 11(7): 765-773.
Dipartimento di Medicina Sperimentale e Clinica G. Salvatore, Università di Catanzaro Magna Graecia, via T. Campanella 115, 88100 Catanzaro, Italy
Dipartimento di Biologia e Patologia Cellulare e Molecolare, c/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Università di Napoli Federico II, via Pansini 5, 80131 Napoli, Italy
IRCCS, Ospedale Pediatrico Bambino Gesù, 00100 Roma, Italy
Istituto di Biostrutture e Bioimmagini, CNR, Università di Napoli Federico II, via Pansini 5, 80131 Napoli, Italy
Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, 410 West 12th Avenue, Columbus, OH 43210, United States
Grupo de Obesidade e Doen as Metab licas, Servi o de Endocrinologia e Metabologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP), Brazil
Departamento de Obesidade da Sociedade Brasileira de Endocrinologia e Metabologia, Brazil
Hospital Brigadeiro, Brazil
R. Alves Guimaraes. 462, CEP 05410-000 - S o Paulo - SP, Brazil
References: Not available.
Lack of the architectural factor HMGA1 causes insulin resistance and diabetes in humans and mice
Type 2 diabetes mellitus is a widespread disease, affecting millions of people globally. Although genetics and environmental factors seem to have a role, the cause of this metabolic disorder is largely unknown. Here we report a genetic flaw that markedly reduced the intracellular expression of the high mobility group A1 (HMGA1) protein, and adversely affected insulin receptor expression in cells and tissues from four subjects with insulin resistance and type 2 diabetes. Restoration of HMGA1 protein expression in subjects' cells enhanced INSR gene transcription, and restored cell-surface insulin receptor protein expression and insulin-binding capacity. Loss of Hmga1 expression, induced in mice by disrupting the Hmga1 gene, considerably decreased insulin receptor expression in the major targets of insulin action, largely impaired insulin signaling and severely reduced insulin secretion, causing a phenotype characteristic of human type 2 diabetes.
Lack of the architectural factor HMGA1 causes insulin resistance and diabetes in humans and mice
No results.
Lack of the architectural factor HMGA1 causes insulin resistance and diabetes in humans and mice