Provided herein are compositions, systems, kits, and methods of indirectly assessing insulin release in a cell.

The present invention provides methods for identifying candidate compounds for limiting development of and/or treating diabetes, and methods for limiting development of and/or treating diabetes.

The invention provides stem cell derived beta-pancreatic cells and animal models of T2D in which cells have been grafted. The stem cells bear a mutated form of SLC30A8 conferring protection or susceptibility to T2D. The cells and animal models can be used for drug screening as well as to provide insights into the mechanism of T2D and potentially new therapeutic and diagnostic targets.

The present disclosure is drawn to methods of diagnosing and classifying pancreatic cancer by examining the expression of particular metabolites that distinguish this disease state from benign disease and periampullary adenocarcinoma.

The present invention provides methods of identifying candidate compounds for the treatment of type I diabetes comprising contacting pancreatic cells with an amount of apolipoprotein CIII (apoCIII) effective to increase intracellular calcium concentration, in the presence of one or more test compounds, and identifying those test compounds that inhibit an apoCIII-induced increase in intracellular calcium concentration in the pancreatic cells. The present invention also provides methods for treating patients with type I diabetes comprising administering to the patient an amount effective of an inhibitor of apoCIII to reduce apoCIII-induced increase in intracellular calcium concentration in pancreatic cells.

The present invention provides improved methods and compositions based on microvesicles for the treatment of various diseases, disorders and conditions. In particular, the present invention encompasses the recognition that microvesicles contain specific microRNAs which may function as intercellular regulators involved in cell or tissue regeneration, remodeling, reconstruction, reprogramming or transdifferentiation. Thus, among other things, the present invention provides methods and compositions based on microvesicles and/or associated microRNAs that provide more predictable and effective therapeutic results.

Methods, kits, compositions, and systems are provided for culturing pluripotent stem cells to produce populations of cells comprising beta-like cells (e.g., pancreatic lineage, glucose-responsive, and/or insulin-producing). In particular, culture conditions are provided that result in the generation of beta-like cells from a starting culture of human pluripotent stem cells.

Microfluidic systems including a housing configured to receive a cartridge, the cartridge including a plurality of wells for receiving one or more biological cells are described herein. The microfluidic systems include a structure with channels for introducing a medium into the housing and through channels the cartridge. Microfluidic systems including a housing configured to receive a cartridge, the housing including channels for loading one or more biological cells within wells of the cartridge are described herein. Three-dimensional scaffolds, devices, and systems comprising such scaffolds that mimic the in vivo structure, physical properties, and protein composition of extracellular matrix surrounding pancreatic islet cells and adipocytes, and the use of such compositions, devices and systems for, e.g., in vitro drug screening and/or toxicity assays, disease modeling, and therapeutic applications are also described herein.

The invention provides, in part, methods for diagnosing a pancreatic -cell disorder, predicting a subject's risk of developing a pancreatic -cell disorder, monitoring pancreatic -cell function or pancreatic -cell mass in a subject at risk of developing a pancreatic -cell disorder, monitoring efficacy of a treatment of a pancreatic -cell disorder in a subject, identifying a subject having an increased risk of developing a pancreatic -cell disorder, selecting a subject for treatment of a pancreatic -cell disorder, selecting a subject for participation in a clinical study, and detecting endoplasmic reticulum stress in a pancreatic -cell. These methods include determining at least one level of soluble mesencephalic astrocyte-derived neurotrophic factor (MANF) in a biological sample from the subject. Also provided are pharmaceutical compositions containing a soluble MANF protein and kits containing an antibody or an antigen-binding antibod fragment that binds specifically to a soluble MANF.

The present invention provides methods of identifying candidate compounds for the treatment of type I diabetes comprising contacting pancreatic cells with an amount of apolipoprotein CIII (apoCIII) effective to increase intracellular calcium concentration, in the presence of one or more test compounds, and identifying those test compounds that inhibit an apoCIII-induced increase in intracellular calcium concentration in the pancreatic cells. The present invention also provides methods for treating patients with type I diabetes comprising administering to the patient an amount effective of an inhibitor of apoCIII to reduce apoCIII-induced increase in intracellular calcium concentration in pancreatic cells.