Open AccessEssential Role of Pten in Body Size Determination and Pancreatic β-Cell Homeostasis In Vivo
Author(s) -
Kinh-Tung T. Nguyen,
Panteha Tajmir,
Chia Hung Lin,
Nicole Liadis,
Xudong Zhu,
Mohammed Eweida,
Gunce Tolasa-Karaman,
Fei Cai,
Rennian Wang,
Tadahiro Kitamura,
Denise D. Belsham,
Michael B. Wheeler,
Akira Suzuki,
Tak W. Mak,
Minna Woo
Publication year - 2006
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00238-06
Subject(s) - pten , biology , tensin , pi3k/akt/mtor pathway , insulin receptor , insulin , protein kinase b , endocrinology , medicine , glucose homeostasis , microbiology and biotechnology , insulin resistance , signal transduction
PTEN (phosphatase with tensin homology) is a potent negative regulator of phosphoinositide 3-kinase (PI3K)/Akt signaling, an evolutionarily conserved pathway that signals downstream of growth factors, including insulin and insulin-like growth factor 1. In lower organisms, this pathway participates in fuel metabolism and body size regulation and insulin-like proteins are produced primarily by neuronal structures, whereas in mammals, the major source of insulin is the pancreatic β cells. Recently, rodent insulin transcription was also shown in the brain, particularly the hypothalamus. The specific regulatory elements of the PI3K pathway in these insulin-expressing tissues that contribute to growth and metabolism in higher organisms are unknown. Here, we report PTEN as a critical determinant of body size and glucose metabolism when targeting is driven by the rat insulin promoter in mice. The partial deletion of PTEN in the hypothalamus resulted in significant whole-body growth restriction and increased insulin sensitivity. Efficient PTEN deletion in β cells led to increased islet mass without compromise of β-cell function. Parallel enhancement in PI3K signaling was found in PTEN-deficient hypothalamus and β cells. Together, we have shown that PTEN in insulin-transcribing cells may play an integrative role in regulating growth and metabolism in vivo.