Understanding of basic mechanisms of beta-cell function and survival: prelude to new diabetes therapies.
Type 1 and type 2 diabetes are both diseases of insulin insufficiency, although they develop by distinct pathways. The recent surge in the incidence of type 2 diabetes and the chronic ailments confronted by patients with either form of the disease highlight the need for better understanding of beta-cell biology. In this review, we present recent work focused on this goal. Our hope is that basic research being conducted in this and other laboratories will ultimately contribute to the development of methods for enhancing beta-cell function and survival in the context of both major forms of diabetes. Our strategy for understanding the beta-cell involves a multidisciplinary approach in which tools from the traditional fields of biochemistry, enzymology, and physiology are teamed with newer technologies from the fields of molecular biology, gene discovery, cell and developmental biology, and biophysical chemistry. We have focused on two important aspects of beta-cell biology in our studies: beta-cell function, specifically the metabolic regulatory mechanisms involved in glucose-stimulated insulin secretion, and beta-cell resistance to immune attack, with emphasis on resistance to inflammatory cytokines and reactive oxygen species.
Newgard
Christopher B
CB
Sarah W. Stedman Nutrition and Metabolism Center, and Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA. newga002@mc.duke.edu
Hohmeier
Hans E
HE
Lu
Danhong
D
Jensen
Mette Valentin
MV
Tran
Veronique V
VV
Chen
Guoxun
G
Burgess
Shawn
S
Sherry
A Dean
AD
D000818:Animals; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D003924:Diabetes Mellitus, Type 2 / Q000628:therapy*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology*; D053583:Interleukin-1beta / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008957:Models, Genetic; D019289:Pyruvic Acid / Q000378:metabolism; D017382:Reactive Oxygen Species
D016207:Cytokines; D007328:Insulin; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; D019289:Pyruvic Acid; D005947:Glucose