We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Augmented Stat5 Signaling Bypasses Multiple Impediments to Lactogen-Mediated Proliferation in Human β-Cells.
- Authors
Hainan Chen; Kleinberger, Jeffrey W.; Takane, Karen K.; Salim, Fatimah; Fiaschi-Taesch, Nathalie; Pappas, Kyrie; Parsons, Ramon; Jing Jiang; Yue Zhang; Hongtao Liu; Peng Wang; Bender, Aaron S.; Frank, Stuart J.; Stewart, Andrew F.; Chen, Hainan; Jiang, Jing; Zhang, Yue; Liu, Hongtao; Wang, Peng
- Abstract
Pregnancy in rodents is associated with a two- to threefold increase in β-cell mass, which is attributable to large increases in β-cell proliferation, complimented by increases in β-cell size, survival, and function and mediated mainly by the lactogenic hormones prolactin (PRL) and placental lactogens. In humans, however, β-cell mass does not increase as dramatically during pregnancy, and PRL fails to activate proliferation in human islets in vitro. To determine why, we explored the human PRL-prolactin receptor (hPRLR)-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5)-cyclin-cdk signaling cascade in human β-cells. Surprisingly, adult human β-cells express little or no PRLR. As expected, restoration of the hPRLR in human β-cells rescued JAK2-STAT5 signaling in response to PRL. However, rescuing hPRLR-STAT5 signaling nevertheless failed to confer proliferative ability on adult human β-cells in response to PRL. Surprisingly, mouse (but not human) Stat5a overexpression led to upregulation of cyclins D1-3 and cdk4, as well as their nuclear translocation, all of which are associated with β-cell cycle entry. Collectively, the findings show that human β-cells fail to proliferate in response to PRL for multiple reasons, one of which is a paucity of functional PRL receptors, and that murine Stat5 overexpression is able to bypass these impediments.
- Subjects
PROLACTIN; PANCREATIC beta cells; LABORATORY rodents; PREGNANCY; PLACENTAL lactogen; JANUS kinases; CYCLINS; CELL proliferation; PROTEIN metabolism; ANIMAL experimentation; BIOCHEMISTRY; CARRIER proteins; CELL lines; CELL physiology; CELL receptors; CELLULAR signal transduction; ISLANDS of Langerhans; PHENOMENOLOGY; MICE; PHOSPHORYLATION; PROTEINS; RESEARCH funding; TRANSFERASES
- Publication
Diabetes, 2015, Vol 64, Issue 11, p3784
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db15-0083