Provided are methods for identifying or monitoring a subject having, or at risk of developing, impaired glucose homeostasis. Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is shown to be a biomarker for impaired glucose homeostasis and/or conditions characterized by β-cell dysfunction. Comparing a test level of CMPF in a subject to a control level identifies subjects having, or at risk of developing, impaired glucose homeostasis. Also provided are methods of causing impaired glucose homeostasis or β-cell dysfunction and methods of screening for compounds that affect the activity of β-cells. Also provided are methods for the treatment of β-cell dysfunction by reducing the physiological levels of CMPF in a subject as well as the use of a OAT modulator for the treatment of β-cell dysfunction.

There is provided herein cell culture mediums for generating organoids, including tumour organoids.

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.

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-α stimulation in a time- and dose-dependent manner and β cell apoptosis is induced through a mitochondrial pathway. TNF-α significantly inhibited glucose-induced preproinsulin precursor mRNA synthesis. Such β 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 invention is based, in part, on the discovery that a polypeptide, referred to herein as Betacam, is selectively expressed on the surface of pancreatic islet cells. Thus, in one aspect, the invention is directed to compositions comprising Betacam or that can be used to detect Betacam. In another aspect, the invention provides methods of detecting (e.g., non-invasively) pancreatic beta cells from a mammalian cell source. Another aspect of the invention is directed to cellular purification of pancreatic beta cells from a heterogeneous cell source of multiple kinds. In another aspect, the invention provides methods of identifying agents that modulate activity of Betacam. In yet another aspect, the invention provides for improved treatment and diagnosis of diabetes.

The present invention relates to a method of characterizing a composition comprising two or more active drug compounds, the method comprising the steps of: a) a composition selection screen (CSS), in which screen a candidate composition comprising two or more active drug compounds is tested against a 3D microtissue derived from one or more cell line, and b) a composition validation screen (CVS), in which screen the candidate composition of step b) is tested against a 3D microtissue derived from a primary patient sample.

The present invention relates to an in vitro method for preparing and producing canine pancreatic islets from immature pancreatic tissue. Such islets express, produce and secrete insulin upon glucose stimulation. The invention further encompasses canine pancreatic islets obtainable according to the present method, islet population of said islets and compositions comprising said islets. It also relates to transduced canine pancreatic islets, or tumours or cells derived thereof. The present invention also concerns the use of said canine pancreatic islets or cells derived thereof for treating a canine pancreatic disorder, such as canine diabetes, or for diagnosing canine diabetes.

Disclosed herein are methods for generating SC-β cells, and isolated populations of SC-β cells for use in various applications, such as cell therapy.

The invention provides use of epalrestat in preparation of pancreatic cancer drugs. The pancreatic cancer drugs are used for inhibiting secretion of exosomes from pancreatic cancer cells. The invention also provides a method for verifying the inhibition effect of epalrestat on secretion of exosomes from pancreatic cancer cells. The method includes steps of: extracting cell supernatant exosomes by using a low-temperature ultracentrifugation method; lysing the collected exosomes, then using a BCA kit to quantify the resulting exosomal protein, and using the measured amount of the protein to reflect the amount of the exosomes; using a transmission electron microscope to verify a double-layer lipid membrane wrapped cup-shaped structure of the exosomes; and detecting exosome protein concentration by protein polyacrylamide gel electrophoresis with Coomassie brilliant blue. The invention provides a novel use of epalrestat, namely the inhibition of exosome secretion. The epalrestat has great application potential in clinical tumor treatment.

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