Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas
A Du, CS Hunter, J Murray, D Noble, CL Cai… - Diabetes, 2009 - Am Diabetes Assoc
A Du, CS Hunter, J Murray, D Noble, CL Cai, SM Evans, R Stein, CL May
Diabetes, 2009•Am Diabetes AssocOBJECTIVE The generation of mature cell types during pancreatic development depends on
the expression of many regulatory and signaling proteins. In this study, we tested the
hypothesis that the transcriptional regulator Islet-1 (Isl-1), whose expression is first detected
in the mesenchyme and epithelium of the developing pancreas and is later restricted to
mature islet cells, is involved in the terminal differentiation of islet cells and maintenance of
islet mass. RESEARCH DESIGN AND METHODS To investigate the role of Isl-1 in the …
the expression of many regulatory and signaling proteins. In this study, we tested the
hypothesis that the transcriptional regulator Islet-1 (Isl-1), whose expression is first detected
in the mesenchyme and epithelium of the developing pancreas and is later restricted to
mature islet cells, is involved in the terminal differentiation of islet cells and maintenance of
islet mass. RESEARCH DESIGN AND METHODS To investigate the role of Isl-1 in the …
OBJECTIVE
The generation of mature cell types during pancreatic development depends on the expression of many regulatory and signaling proteins. In this study, we tested the hypothesis that the transcriptional regulator Islet-1 (Isl-1), whose expression is first detected in the mesenchyme and epithelium of the developing pancreas and is later restricted to mature islet cells, is involved in the terminal differentiation of islet cells and maintenance of islet mass.
RESEARCH DESIGN AND METHODS
To investigate the role of Isl-1 in the pancreatic epithelium during the secondary transition, Isl-1 was conditionally and specifically deleted from embryonic day 13.5 onward using Cre/LoxP technology.
RESULTS
Isl-1–deficient endocrine precursors failed to mature into functional islet cells. The postnatal expansion of endocrine cell mass was impaired, and consequently Isl-1 deficient mice were diabetic. In addition, MafA, a potent regulator of the Insulin gene and β-cell function, was identified as a direct transcriptional target of Isl-1.
CONCLUSIONS
These results demonstrate the requirement for Isl-1 in the maturation, proliferation, and survival of the second wave of hormone-producing islet cells.
Am Diabetes Assoc