Pancreatic β-cell proliferation in obesity.
Because obesity rates have increased dramatically over the past 3 decades, type 2 diabetes has become increasingly prevalent as well. Type 2 diabetes is associated with decreased pancreatic β-cell mass and function, resulting in inadequate insulin production. Conversely, in nondiabetic obesity, an expansion in β-cell mass occurs to provide sufficient insulin and to prevent hyperglycemia. This expansion is at least in part due to β-cell proliferation. This review focuses on the mechanisms regulating obesity-induced β-cell proliferation in humans and mice. Many factors have potential roles in the regulation of obesity-driven β-cell proliferation, including nutrients, insulin, incretins, hepatocyte growth factor, and recently identified liver-derived secreted factors. Much is still unknown about the regulation of β-cell replication, especially in humans. The extracellular signals that activate proliferative pathways in obesity, the relative importance of each of these pathways, and the extent of cross-talk between these pathways are important areas of future study.
Division of Endocrinology, Department of Medicine, and.
Amelia K
AK
Linnemann
Division of Endocrinology, Department of Medicine, and School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI; and.
Mieke
M
Baan
Division of Endocrinology, Department of Medicine, and William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin dbd@medicine.wisc.edu.
Dawn Belt
DB
Davis
D000818:Animals; D049109:Cell Proliferation; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000166:cytology*; D008099:Liver / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
D043562:Receptors, G-Protein-Coupled