p53-upregulated modulator of apoptosis (PUMA) is a biomarker associated with islet cell health. If PUMA is low, islet cells are typically healthy. If PUMA is high, islet cells are typically unhealthy or dying. PUMA may be measured by either measuring its nucleic or amino acid. PUMA mRNA may be induced by TNF- stimulation in a time- and dose-dependent manner and cell apoptosis is induced through a mitochondrial pathway. TNF- significantly inhibited glucose-induced preproinsulin precursor mRNA synthesis. Such cell stress signaling in human islets indicates overall state of islet health and, ultimately, the risk of onset and/or degree of severity of both type 1 and type 2 diabetes mellitus.

The present invention provides a method for diagnosing a disease or disorder selected from the group consisting of insulin resistance, a metabolic disorder, diabetes and pre-diabetes in a subject. The method comprises the step of determining the level of a compound represented by structural formula (VI): or a salt thereof. Compositions and method of making thereof are also described.

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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 present invention relates to the use of the biomarker Flattop (Fltp) for distinguishing mature cells from immature progenitor cells. The present invention further relates to a method for distinguishing a mature cell from an immature progenitor cell, the method comprising: determining the presence or absence of the biomarker Flattop (Fltp) in a cell; wherein the presence of Fltp in the cell indicates that the cell is a mature cell and wherein the absence of Fltp in the cell indicates that the cell is an immature progenitor cell. Furthermore, the present invention relates to a method of identifying a compound suitable for differentiating immature progenitor cells into mature cells as well as to a method of identifying a compound suitable for preventing the de-differentiating of mature cells.

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.

Disclosed herein are methods and compositions for treating, as well as identifying potential therapeutics for, cancers or diabetes, with compounds that inhibit the activity of menin, preferably the compounds are capable of inhibiting MLL binding to menin.

The invention relates to methods for differentiating progenitor cells into insulin producing pancreatic islet cells and compositions and methods for using such cells.

It is an object of the present invention to provide a method for efficiently directing differentiation into insulin-producing cells in a xeno-free culture system. According to the present invention, there is provided a method for directed differentiation into insulin-producing cells, comprising culturing stem cells in the following steps (1) to (5): (1) a step of culturing stem cells in a medium comprising an activator of activin receptor-like kinase-4/-7 and a GSK3 inhibitor and then culturing in a medium comprising an activator of activin receptor-like kinase-4/-7; (2) a step of culturing the cells obtained in step (1) in a medium comprising a hedgehog signaling inhibitor and an FGF; (3) a step of culturing the cells obtained in step (2) in a medium comprising a retinoic acid receptor agonist, a hedgehog signaling inhibitor and a BMP signaling inhibitor; (4) a step of culturing the cells obtained in step (3) in a medium comprising a TGF- type I activin receptor-like kinase-4/-5/-7 inhibitor and a BMP signaling inhibitor; and (5) a step of culturing the cells obtained in step (4) in a medium comprising a phosphodiesterase inhibitor.

Provided herein are methods of differentiating stem cells via modulating miR-124, and the differentiated cells thereby. Also provided herein are methods for the treatment of diseases using the differentiated cells.

Cell culture mediums for generating organoids, including tumour organoids. Specifically, such mediums comprise: a cell culture medium; an antioxidant; a serum free supplement; an insulin receptor agonist; a glucocorticoid; and an FGFR agonist. Other aspects involve methods of generating tumour organoids from tumours. Such methods can comprise generating pancreatic progenitor organoids from pluripotent stem cells, pancreatic lineage committed progenitors.