Type 2 diabetes mellitus is a chronic metabolic disease that is predominately characterized by hyperglycaemia and dyslipidemia, and improvement of glucose and lipid metabolism disorders is a potent therapeutic strategy against this metabolic disease. 

Researchers from Shanghai Institute of Materia Medica discovered that Latanoprost, a clinical drug for treating primary open-angle glaucoma and intraocular hypertension, effectively ameliorated glucose and lipid disorders in the two mouse models of type 2 diabetes.

In this study, researchers constructed screening platforms targeting RXRa/PPARg heterodimer and AMPK, and the ‘old drug’ latanoprost was identified from in-house existing drug library with features by inhibiting RXRa/PPARg heterodimer transcription and promoting AMPK phosphorylation.

Cell-based assays on 3T3-L1 adipocytes and C2C12 myotubes demonstrated that latanoprost could promote glucose uptake, inhibit pre-adipocyte differentiation and regulate the main genes responsible for glucose and lipid metabolism, then the animal model-based assays with db/db and ob/ob mice indicated latanoprost potently decreased the levels of fasting blood glucose, HbA1c, fructosamine (FMN), NEFA and total cholesterol, and effectively improved glucose tolerance and glucose/lipid metabolism-related genes in vivo. Their work strongly highlights the potential of latanoprost in the treatment of type 2 diabetes mellitus.

This research was performed by WANG Gaihong, associated Prof. CHENJing and others from the research group of Prof. SHEN Xu in SIMM. On September 4th, the work has been published online on Diabetologia. 

Currently, the related findings have been applied for Chinese patents.

Through the inhibition of the transcription of RXRa/PPARg heterodimer and promotion of AMPK phosphorylation, Latanoprost effectively ameliorated glucose and lipid disorders in diabetic mice. (Image By SIMM)