Human duct cells contribute to β cell compensation in insulin resistance.
“Human Duct Cells Contribute To Β Cell Compensation In Insulin Resistance.”. Jci Insight..
|Center||Joslin Diabetes Center|
|Author||Ercument Dirice, Dario F De Jesus, Sevim Kahraman, Giorgio Basile, Raymond Ws Ng, Abdelfattah El Ouaamari, Adrian Kee Keong Teo, Shweta Bhatt, Jiang Hu, Rohit N Kulkarni|
|Keywords||Cell Biology, diabetes, Endocrinology, Islet cells, Mouse models|
The identification of new sources of β cells is an important endeavor with therapeutic implications for diabetes. Insulin resistance, in physiological states such as pregnancy or in pathological states such as type 2 diabetes (T2D), is characterized by a compensatory increase in β cell mass. To explore the existence of a dynamic β cell reserve, we superimposed pregnancy on the liver-specific insulin receptor-KO (LIRKO) model of insulin resistance that already exhibits β cell hyperplasia and used lineage tracing to track the source of new β cells. Although both control and LIRKO mice displayed increased β cell mass in response to the relative insulin resistance of pregnancy, the further increase in mass in the latter supported a dynamic source that could be traced to pancreatic ducts. Two observations support the translational significance of these findings. First, NOD/SCID-γ LIRKO mice that became pregnant following cotransplantation of human islets and human ducts under the kidney capsule showed enhanced β cell proliferation and an increase in ductal cells positive for transcription factors expressed during β cell development. Second, we identified duct cells positive for immature β cell markers in pancreas sections from pregnant humans and in individuals with T2D. Taken together, during increased insulin demand, ductal cells contribute to the compensatory β cell pool by differentiation/neogenesis.
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