Overexpression of Pref-1 in pancreatic islet β-cells in mice causes hyperinsulinemia with increased islet mass and insulin secretion.
Preadipocyte factor-1 (Pref-1) is made as a transmembrane protein containing EGF-repeats at the extracellular domain that can be cleaved to generate a biologically active soluble form. Pref-1 is found in islet β-cells and its level has been reported to increase in neonatal rat islets upon growth hormone treatment. We found here that Pref-1 can promote growth of pancreatic tumor derived AR42J cells. To examine Pref-1 function in pancreatic islets in vivo, we generated transgenic mouse lines overexpressing the Pref-1/hFc in islet β-cells using rat insulin II promoter (RIP). These transgenic mice exhibit an increase in islet mass with higher proportion of larger islets in pancreas compared to wild-type littermates. This is in contrast to pancreas from Pref-1 null mice that show higher proportion of smaller islets. Insulin expression and insulin secretion from pancreatic islets from RIP-Pref-1/hFc transgenic mice are increased also. Thus, RIP-Pref-1/hFc transgenic mice show normal glucose levels but with higher plasma insulin levels in both fasting and fed conditions. These mice show improved glucose tolerance. Taken together, we conclude Pref-1 as a positive regulator of islet β-cells and insulin production.
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
Yuhui
Y
Wang
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
Kichoon
K
Lee
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
Yang Soo
YS
Moon
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
Maryam
M
Ahmadian
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
Kee-Hong
KH
Kim
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
Karim
K
Roder
Department of Molecular Cell Biology, University of California, Berkeley, CA 94720, USA.
Chulho
C
Kang
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA. Electronic address: hsul@berkeley.edu.
Hei Sook
HS
Sul
D000818:Animals; D002135:Calcium-Binding Proteins; D049109:Cell Proliferation; D005260:Female; D006946:Hyperinsulinism / Q000378:metabolism* / Q000473:pathology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015854:Up-Regulation
D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins
Diabetes; Hyperinsulinemia; Insulin secretion; Islet β-cells; Pref-1/Dlk1; Transgenic mice