Uncoupling Protein-2 Negatively Regulates Insulin Secretion and Is a Major Link between Obesity, β Cell Dysfunction, and Type 2 Diabetes
Copyright policy )Uncoupling Protein-2 Negatively Regulates Insulin Secretion and Is a Major Link between Obesity, β Cell Dysfunction, and Type 2 Diabetes
beta cells sense glucose through its metabolism and the resulting increase in ATP, which subsequently stimulates insulin secretion. Uncoupling protein-2 (UCP2) mediates mitochondrial proton leak, decreasing ATP production. In the present study, we assessed UCP2's role in regulating insulin secretion. UCP2-deficient mice had higher islet ATP levels and increased glucose-stimulated insulin secretion, establishing that UCP2 negatively regulates insulin secretion. Of pathophysiologic significance, UCP2 was markedly upregulated in islets of ob/ob mice, a model of obesity-induced diabetes. Importantly, ob/ob mice lacking UCP2 had restored first-phase insulin secretion, increased serum insulin levels, and greatly decreased levels of glycemia. These results establish UCP2 as a key component of beta cell glucose sensing, and as a critical link between obesity, beta cell dysfunction, and type 2 diabetes.
- Yale University United States
- Brigham and Women's Faulkner Hospital United States
- University of Toronto Canada
- University of Prince Edward Island Canada
- Beth Israel Deaconess Medical Center United States
Blood Glucose, Male, Mice, Knockout, Biochemistry, Genetics and Molecular Biology(all), Body Weight, Membrane Transport Proteins, Mice, Obese, Ion Channels, Disease Models, Animal, Islets of Langerhans, Mice, Adenosine Triphosphate, Diabetes Mellitus, Type 2, Hyperglycemia, Gene Targeting, Insulin Secretion, Diabetes Mellitus, Animals, Homeostasis, Humans, Insulin
Blood Glucose, Male, Mice, Knockout, Biochemistry, Genetics and Molecular Biology(all), Body Weight, Membrane Transport Proteins, Mice, Obese, Ion Channels, Disease Models, Animal, Islets of Langerhans, Mice, Adenosine Triphosphate, Diabetes Mellitus, Type 2, Hyperglycemia, Gene Targeting, Insulin Secretion, Diabetes Mellitus, Animals, Homeostasis, Humans, Insulin
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).854 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 0.1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 0.1%
Citations provided by BIP!Popularity provided by BIP!