Defective insulin secretion in pancreatic beta cells lacking type 1 IGF receptor.
Defective insulin secretion is a feature of type 2 diabetes that results from inadequate compensatory increase of beta cell mass and impaired glucose-dependent insulin release. beta cell proliferation and secretion are thought to be regulated by signaling through receptor tyrosine kinases. In this regard, we sought to examine the potential proliferative and/or antiapoptotic role of IGFs in beta cells by tissue-specific conditional mutagenesis ablating type 1 IGF receptor (IGF1R) signaling. Unexpectedly, lack of functional IGF1R did not affect beta cell mass, but resulted in age-dependent impairment of glucose tolerance, associated with a decrease of glucose- and arginine-dependent insulin release. These observations reveal a requirement of IGF1R-mediated signaling for insulin secretion.
Xuan
Shouhong
S
Department of Genetics and Development, College of Physicians & Surgeons, Columbia University, New York, New York, USA.
Kitamura
Tadahiro
T
Nakae
Jun
J
Politi
Katerina
K
Kido
Yoshiaki
Y
Fisher
Peter E
PE
Morroni
Manrico
M
Cinti
Saverio
S
White
Morris F
MF
Herrera
Pedro L
PL
Accili
Domenico
D
Efstratiadis
Argiris
A
D000818:Animals; D005089:Exocytosis; D051273:Glucose Transporter Type 2; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D017526:Receptor, IGF Type 1