Genetic disruption of sod1 gene causes glucose intolerance and impairs b-cell function
- Resource Type
- Authors
- Ralph A. DeFronzo; Giovanna Muscogiuri; Bogdan Balas; Cristina Aguayo-Mazzucato; Nicolas Musi; Robert L. Reddick; Mengyao E. Li; Adam B. Salmon; Holly Van Remmen; Sara M. Reyna; Rodolfo Guardado-Mendoza; Andrea Giaccari; Gordon C. Weir
- Source
- Diabetes
- Subject
- Blood Glucose
Male
stress ossidativo
metabolismo glucidico
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Type 2 diabetes
medicine.disease_cause
Mice
0302 clinical medicine
Superoxide Dismutase-1
Insulin-Secreting Cells
Insulin Secretion
Glucose homeostasis
Insulin
tolleranza glucidica
test di tolleranza glucidica
Original Research
2. Zero hunger
Mice, Knockout
0303 health sciences
Glucose tolerance test
medicine.diagnostic_test
dieta iperlipidica
medicine.anatomical_structure
cellule secernenti insulina
medicine.medical_specialty
Knockout
030209 endocrinology & metabolism
Biology
insulino-resistenza
modello animale
Diet, High-Fat
Pathophysiology
Superoxide dismutase
03 medical and health sciences
Insulin resistance
Internal medicine
superossido dismutasi
Glucose Intolerance
Internal Medicine
medicine
Animals
insulina
030304 developmental biology
Animal
Superoxide Dismutase
Pancreatic islets
Settore MED/13 - ENDOCRINOLOGIA
Oxidative Stre
Glucose Tolerance Test
medicine.disease
Diet
Oxidative Stress
High-Fat
Endocrinology
Insulin-Secreting Cell
biology.protein
Insulin Resistance
Oxidative stress
- Language
- English
Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. b-Cell function was determined with the hyperglycemic clamp and morphometric analysis of pancreatic islets. Genetic ablation of SOD1 caused glucose intolerance, which was associated with reduced in vivo b-cell insulin secretion and decreased b-cell volume. Peripheral and hepatic insulin sensitivity were not significantly altered in SOD1-null mice. High-fat diet caused glucose intolerance in WT mice but did not further worsen the glucose intolerance observed in standard chow-fed SOD1-null mice. Our findings suggest that oxidative stress per se does not play a major role in the pathogenesis of insulin resistance and demonstrate that oxidative stress caused by SOD1 ablation leads to glucose intolerance secondary to b-cell dysfunction. © 2013 by the American Diabetes Association.