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The addition of glucagon delivery to a closed-loop system with automated exercise detection reduces hypoglycemia in physically active adults with type 1 diabetes.

We previously presented evidence that proliferative human islet precursor cells may be derived in vitro from adult islets by epithelial-to-mesenchymal transition (EMT) and show here that similar fibroblast-like cells can be derived from mouse islets. These mouse cell populations exhibited changes in gene expression consistent with EMT. Both C-peptide and insulin mRNAs were undetectable in expanded cultures of mouse islet-derived precursor cells (mIPCs). After expansion, mIPCs could be induced to migrate into clusters and differentiate into hormone-expressing islet-like aggregates. Although early morphological changes suggesting EMT were observed by time-lapse microscopy when green fluorescent protein-labeled beta cells were placed in culture, the expanded precursor cell population was not fluorescent. Using two mouse models in which beta cells were permanently made either to express alkaline phosphatase or to have a deleted M 3 muscarinic receptor, we provide evidence that mIPCs in long term culture are not derived from beta cells.Investigators worldwide are conducting pre-clinical research aimed at employing in vitro systems to generate large numbers of islets of Langerhans (or beta cells) (1,2). Although beta cells proliferate in vivo (3) and in vitro (4), well-differentiated beta cells do not proliferate rapidly in vitro. Therefore, islet (or beta cell) precursor cells are being studied for this purpose based on the concept that undifferentiated precursor cells can be expanded exponentially and then induced to differentiate into islet-like cells. We (5-7) and others (8-12) have derived islet precursor cells from adult human islet preparations. However, insights into the processes involved in derivation, expansion and differentiation of these human precursor cells are limited. Assuming conservation across species, similar precursor cells derived from nonhuman islets could be used to study these processes further. For example, transgenic or knockout mice could be used to delineate signal transduction pathways involved in proliferation and differentiation of precursor cells and thereby identify targets for regulation by drugs.We provided evidence previously that precursor cells from human islets may be derived by in vitro epithelial-to-mesenchymal transition (EMT) of insulin-expressing cells (5). The origin of these cells was uncertain because individual human insulin-expressing cells could not be identified and followed in culture. In this report, transgenic mice are used for this purpose. We demonstrate that cells similar to human islet-derived precursor cells (IPCs) (5) can be derived from preparations of mouse islets. Like human IPCs (hIPCs), these cells can proliferate for over 20 doublings and after expansion can be differentiated into clusters of hormone-expressing Corresponding Author: Marvin C. Gershengorn, Scientific Director, NIDDK, National Institutes of Health, 50 South Drive, Bethesda, MD 20892-8029, USA, Tel: 301-451-6305, Fax: 301-480-4214, E-mail: marving@intra.niddk.nih.gov Publisher's...

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