Qilin Long, Yuxin Wu, Lei Wang, Tianbao Chen and Chris Shaw
Department of Pharmacy, Queen's University Belfast, Belfast, United Kingdom
A novel peptide, QUB1999, identified in Phyllomedusa burmeisteri skin, possesses insulintropic activity using multiple signalling pathways Insulin is one of the most important hormones regulating energy metabolism and it acts by triggering a set of intracellular kinases that predominantly modulate target tissues for the maintenance of blood glucose and lipid homeostasis. Failure or insufficiency of insulin secretion from pancreatic β cells, can subsequently contribute to the development of type 2 diabetes mellitus (T2DM). Here, we report a novel peptide, named QUB1999, which induces a dose-dependent insulinotropic effect in the rat pancreatic β cell line, BRIN-BD11. Lactate dehydrogenase measurements implied that QUB1999-induced insulin release was independent of cell membrane degradation. To examine the molecular mechanism, we employed the potassium channel activator, diazoxide, the calcium channel inhibitor, verapamil, and calcium-free medium. The results indicated that the influx of extracellular calcium, mediated by KATP-[K+] channel induced depolarisation, plays a dominant role in stimulating insulin release, but nevertheless, QUB1999 could also enhance insulin secretion through other signalling pathways. Taken together, we confirmed that the novel peptide, QUB1999, from Phyllomedusa burmeisteri skin, exhibited potent insulinotropic activity through use of multiple signalling pathways without altering the integrity of the cell membrane. This peptide may thus represent a competitive drug candidate for development of novel anti-diabetic agents.
Keywords: Peptide, Insulin release, Potassium channel, Anti-diabetic, Calcium.