Endocrine Abstracts

Fibroblast growth factor 21 (FGF21) is an emerging regulator of energy homeostasis and a novel target for the development of therapies to treat diabetes, cardiovascular disease, and obesity. FGF21 was discovered in an in vitro high throughput screen. It was later shown to have impressive metabolic pharmacology including glucose, lipid, and body weight lowering effects in a variety of animal models, including non-human primates. When tested clinically an FGF21-based an...

Abstract: Inflammation plays a contributing role in the pathogenesis of several metabolic disorders, including type 2 diabetes and obesity. Intriguingly, obesogenic diets induce markers of hypothalamic inflammation and neuronal injury in both rodents and humans, suggesting that targeting inflammatory pathways in the hypothalamus might represent a novel strategy to control energy metabolism. Unfortunately, the majority of steroid-based anti-inflammatory drugs are fraught with a...

Promiscuous multi-agonists that simultaneously activate two or three key receptors (incretin- and/or glucagon receptor) were recently shown to improve glycemic control in mice. Here we investigated the underlying mechanisms of multi-agonists to enhance insulin secretion in murine islets and human pancreatic β-cells. These mixed agonists display a greater potency in cAMP signaling as compared to the native incretins. However, pharmacological blockade of cAMP signaling only...