Abstract: The invention features compositions comprising in vitro generated beta cells capable of glucose-stimulated insulin secretion, methods of inducing beta cell maturation from embryonic or induced pluripotent stem cell-derived beta-like cells, and methods of using in vitro generated beta cells for the treatment of type 1 diabetes, type 2 diabetes, or a related disorder.

Abstract: Novel compounds having a formula embodiments of a method of making the same, and of a composition comprising them are disclosed herein. Also disclosed are embodiments of a method of treating or preventing a metabolic disorder in a subject, comprising administering to a subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and treating or preventing a metabolic disorder in the subject. Additionally disclosed are embodiments of a method of treating or preventing inflammation in an intestinal region of a subject, comprising administering to the subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and thereby treating or preventing inflammation in the intestinal region of the subject.

Abstract: The invention features compositions comprising in vitro generated beta cells capable of glucose-stimulated insulin secretion, methods of inducing beta cell maturation from embryonic or induced pluripotent stem cell-derived beta-like cells, and methods of using in vitro generated beta cells for the treatment of type 1 diabetes, type 2 diabetes, or a related disorder.

Abstract: Disclosed herein are methods of improving muscular health, such as enhancing muscle regeneration, maintenance, or repair. In some examples, the method includes administering to the subject an effective amount of an agent capable of increasing activity or expression of estrogen receptor-related gamma (ERR?), related receptors ERR? or ?, or ERR-regulated metabolic and angiogenic genes, thereby enhancing muscle regeneration, maintenance, or repair. In some examples, the methods are utilized to treat a subject with one or more signs or symptoms of muscular dystrophy, such as, but not limited to Duchenne muscular dystrophy. In some examples, the disclosed methods further include selecting a subject in need of enhancing muscle regeneration, maintenance, or repair.

Abstract: The invention features compositions comprising in vitro generated beta cells capable of glucose-stimulated insulin secretion, methods of inducing beta cell maturation from embryonic or induced pluripotent stem cell-derived beta-like cells, and methods of using in vitro generated beta cells for the treatment of type 1 diabetes, type 2 diabetes, or a related disorder.

Abstract: Provided herein are methods and compositions for improving muscle performance and increasing endurance. Agonists of AMP-activated protein kinase (AMPK) and agonists of peroxisome proliferator-activated receptor delta (PPAR?) can be used in such treatments.

Abstract: Provided are methods of promoting browning of white adipose tissue (WAT) in a subject. Such methods can include administering to a subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of fexaramine in combination with a therapeutically effective amount of a compound that mimics or increases sympathetic nervous system activity (e.g., one or more beta-adrenergic agonists and/or compounds that increase epinephrine secretion).

Abstract: This application provides methods of increasing vascularization, muscle performance, muscle rehabilitation, and/or mitochondrial activity in subjects in need thereof, by administering a therapeutically effective amount of one or more agents that increases ERR? activity to the subject. Such agents can include one or more ERR? agonists. In some examples the method does not require that the subject exercise, and as such, the subject may be sedentary (such as bedridden or in a wheelchair).

Abstract: The present disclosure provides FGF1 mutant proteins, such as those having an N-terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Such mutant FGF1 proteins can be part of a chimeric protein that includes a ?-Klotho-binding protein, an FGFR1c-binding protein, a ?-Klotho-binding protein and a FGFR1c-binding protein, a C-terminal region from FGF19 or FGF21. In some examples, mutant FGF1 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.

Abstract: This application provides methods of increasing vascularization, muscle performance, muscle rehabilitation, and/or mitochondrial activity in subjects in need thereof, by administering a therapeutically effective amount of one or more agents that increases ERR? activity to the subject. Such agents can include one or more ERR? agonists. In some examples the method does not require that the subject exercise, and as such, the subject may be sedentary (such as bedridden or in a wheelchair).

Abstract: Disclosed herein are methods for enhancing one or more effects of exercise in a subject by administering a PPAR? agonist (e.g., GW1516) to the subject in combination with an exercise program. Also disclosed are gene expression profiles unique to the combination of agonist-induced PPAR? activation and exercise. Such profiles are useful, at least, in methods for identifying the use of performance-enhancing drugs in exercised subjects (such as, professional or athletes). Direct interactions between PPAR? and exercised-induced kinases (e.g., AMPK or its subunits, AMPK ?1 and/or AMPK ?2) also are disclosed. Such protein-protein interactions provide new targets for identification of useful compounds.

Abstract: This application provides methods of increasing vascularization, muscle performance, muscle rehabilitation, and/or mitochondrial activity in subjects in need thereof, by administering a therapeutically effective amount of one or more agents that increases ERR? activity to the subject. Such agents can include one or more ERR? agonists. In some examples the method does not require that the subject exercise, and as such, the subject may be sedentary (such as bedridden or in a wheelchair).

Abstract: This disclosure concerns the use of agonists of AMP-activated protein kinase (AMPK) for improving exercise and modifying energy metabolism in a subject. The disclosure also relates to a combination of AMPK and peroxisome proliferator-activated receptor (PPAR) ? agonists for improving exercise performance in a subject, methods for identifying substance-enhanced exercise performance in a subject, and methods for identifying compounds that affect the interaction of PPAR? with exercise-induced kinases.

Abstract: Disclosed herein are methods for enhancing one or more effects of exercise in a subject by administering a PPAR? agonist (e.g., GW1516) to the subject in combination with an exercise program. Also disclosed are gene expression profiles unique to the combination of agonist-induced PPAR? activation and exercise. Such profiles are useful, at least, in methods for identifying the use of performance-enhancing drugs in exercised subjects (such as, professional or athletes). Direct interactions between PPAR? and exercised-induced kinases (e.g., AMPK or its subunits, AMPK ?1 and/or AMPK ?2) also are disclosed. Such protein-protein interactions provide new targets for identification of useful compounds.