Supaglutide alleviates hepatic steatosis in monkeys with spontaneous MASH.

Background: Glucagon-like peptide 1 (GLP-1) is an incretin hormone and plays an important role in regulating glucose homeostasis. GLP-1 has a short half-life due to degrading enzyme dipeptidyl peptidase-IV and rapid kidney clearance, which limits its clinical application as a therapeutic agent. We demonstrated previously that supaglutide, a novel long-acting GLP-1 analog, exerted hypoglycemic, hypolipidemic, and weight loss effects in type 2 diabetic db/db mice, DIO mice, and diabetic monkeys.

Causal effects of non-alcoholic fatty liver disease on osteoporosis: a Mendelian randomization study.

Background: Osteoporosis (OP) is a systemic skeletal disease characterized by compromised bone strength leading to an increased risk of fracture. There is an ongoing debate on whether non-alcoholic fatty liver disease (NAFLD) is an active contributor or an innocent bystander in the pathogenesis of OP. The aim of this study was to assess the causal association between NAFLD and OP.

Combined therapy of GABA and sitagliptin prevents high-fat diet impairment of beta-cell function.

We recently demonstrated that combined therapy of GABA and sitagliptin promoted beta-cell proliferation, and decreased beta-cell apoptosis in a multiple low-dose streptozotocin (STZ)-induced beta-cell injury mouse model. In this study, we examined whether this combined therapy is effective in ameliorating the impairment of beta-cell function caused by high-fat diet (HFD) feeding in mice. Male C57BL/6J mice were fed normal chow diet, HFD, or HFD combined with GABA, sitagliptin, or both drugs.

Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations.

The α-Klotho protein (henceforth denoted Klotho) has antiaging properties, as first observed in mice homozygous for a hypomorphic gene (). These mice have a shortened lifespan, stunted growth, renal disease, hyperphosphatemia, hypercalcemia, vascular calcification, cardiac hypertrophy, hypertension, pulmonary disease, cognitive impairment, multi-organ atrophy and fibrosis. Overexpression of Klotho has opposite effects, extending lifespan.