Pancreatic β-Cell Proliferation in Obesity

• Published in: Advances in nutrition (Bethesda, Md.) Vol. 5; no. 3; pp. 278 - 288
• Main Authors: Linnemann, Amelia K., Baan, Mieke, Davis, Dawn Belt
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2014; American Society for Clinical Nutrition
• Subjects: Animals; Cell Proliferation; Diabetes Mellitus, Type 2 - metabolism; Diet, High-Fat - adverse effects; Disease Models, Animal; hepatocyte growth factor; Hepatocytes - metabolism; Humans; hyperglycemia; Hyperglycemia - metabolism; insulin; Insulin Resistance; Insulin-Secreting Cells - cytology; islets of Langerhans; Liver - metabolism; mice; noninsulin-dependent diabetes mellitus; nutrients; obesity; Obesity - metabolism; Receptors, G-Protein-Coupled - metabolism; PCNA; ROCK; MIN-6; GIPR; GLPR; IRS; JAK/STAT; EGFR; DPP4; GSK-3β; CREB; PI3K; mTOR; INS-1; G protein; GLUT2; GLP-1; HGF; PKA; EP3; IR; PPARγ; GIP; ChREBP; CAMK4; AMPK; GPCR; BTBR; mTORC1; BrdU; FoxO1; Rgs
• ISSN: 2161-8313; 2156-5376; 2156-5376
• DOI: 10.3945/an.113.005488

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.