Disclosed herein are methods of increasing cell proliferation in a population of pancreatic beta cells. Also disclosed are methods of treating a subject for a condition associated with insufficient insulin secretion. Also disclosed is a composition comprising a DYRK1 A inhibitor and a GLP1R agonist. The disclosure further describes a method of regenerating pancreatic beta cells in a transplant patient.

The present disclosure provides cell-based compositions for treating diabetes, methods for identifying cells that preferentially differentiate into endoderm cells, and methods for preparing insulin-producing pancreatic cells, as well as related methods of use for treating diseases related to insulin deficiency.

An interference image acquisition apparatus includes a light source, a beam splitter, a second reflection mirror, an imager, and a first reflection mirror. A cell is placed on one side of a transparent material, and the first reflection mirror is placed on the other side of the transparent material. In a two-beam interferometer, an optical path difference between an optical path length of a first light beam reflected by the first reflection mirror and an optical path length of a second light beam reflected by the second reflection mirror is set to a coherence length of light output from the light source or less. The imager acquires an interference image in a state in which the cell is placed at a position conjugate to an imaging plane in a first optical system between the imaging plane and the first reflection mirror.

An object of the present invention is to provide a method for producing insulin-producing cells having sufficient glucose responsiveness from mesenchymal stem cells, an insulin-producing cell having sufficient glucose responsiveness, a cell structure containing the insulin-producing cell, and a pharmaceutical composition. According to the present invention, there is provided a method for producing an insulin-producing cell from a mesenchymal stem cell, including (a) a step of producing a cell structure by incubating a plurality of biocompatible macromolecular blocks and a plurality of mesenchymal stem cells, and (b) a step of culturing one or more of the mesenchymal stem cells before the incubation in the step (a), the mesenchymal stem cell in the incubation in the step (a), or the cell structure produced in the step (a) in a medium containing the GLP-1 receptor agonist, and (c) a step of culturing the cell structure obtained in the step (a) or the step (b) in a medium containing the water-soluble vitamin and the hepatocyte growth factor.

The invention provides novel compounds, in particular peptide and peptide analogs, which exhibit functionalities useful for treating a variety of diseases and conditions, particularly diseases and conditions relating to diabetes. The compounds of the invention are also useful for treating impaired pancreatic function, treating metabolic diseases, ex vivo islet induction, expansion and proliferation for transplantation, increasing the survival of transplanted islets in vivo, promoting neuroprotection or nerve regeneration, promoting liver regeneration, and inhibiting inflammation.

The invention relates inter alia to a method for differentiating a muscle progenitor cell, comprising the step of: culturing a muscle progenitor cell in a serum-free medium for differentiating a muscle progenitor cell, wherein said serum-free medium comprises at least one differentiation inducer selected from the group consisting of a lysophosphatidic acid receptor 1 (LPAR1) agonist, a lysophosphatidic acid receptor 3 (LPAR3) agonist, an oxytocin receptor (OXTR) agonist, a glucagon receptor (GCGR) agonist, a lactate and a Notch signaling pathway inhibitor.

The invention provides for methods of differentiating pancreatic endocrine cells into pancreatic beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A. These pancreatic beta cells may be obtained by step-wise differentiation of pluripotent stem cells. The pancreatic beta cells exhibit glucose-dependent mitochondrial respiration and glucose-stimulated insulin secretion similar to islet cells.

This document provides methods and materials related to generating human cells capable of producing insulin in response to glucose or GLP-1. For example, methods and materials for introducing nucleic acid vectors into human stem cells (e.g., human induced pluripotent stem cells) at particular stages of differentiation to create human cells having the ability to produce and secrete human insulin in response to glucose, GLP-1, or both glucose and GLP-1 as measured by a sensitive perifusion assay are provided.

The invention provides for methods of differentiating pancreatic endocrine cells into pancreatic beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A. These pancreatic beta cells may be obtained by step-wise differentiation of pluripotent stem cells. The pancreatic beta cells exhibit glucose-dependent mitochondrial respiration and glucose-stimulated insulin secretion similar to islet cells.

The present invention relates to methods of generating a population of beta cells from a population of alpha cells, by contacting said population of alpha cells with GABA or a GABA receptor agonist, in combination with a monoclonal glucagon neutralizing antibody or other alpha cell mass regulating compounds, for an improved diabetes therapy.