The novel roles of glucagon-like peptide-1, angiotensin II, and vitamin D in islet function.

ABSTRACT

Pancreatic islets secrete multiple factors that act as endocrine, paracrine, and/or autocrine pathways in regulating pancreatic endocrine function. As such, the islets perform critical biological activities in synthesizing metabolic peptide hormones, notably insulin and regulating body glucose homeostasis. These functions are controlled by various conditions and signaling molecules, particularly nutrients like glucose levels. However, more and more clinically relevant regulators, including molecules which stimulate islet beta-cell metabolism, regulate beta-cell [Ca(2+)] homeostasis and related channels or adjust beta-cell membrane, and nuclear receptors activity continue to be discovered and characterized. Of great interest in this context, glucagon-like peptide-1 can improve glycemic control by regulating insulin secretion and islet cell mass; vitamin D can regulate islet physiology directly by binding its receptors; in addition, the peptide hormone angiotensin II has been implicated in islet function and exhibits effects on islet cell secretion as well as cell mass. In this chapter, these three novel regulators in islet function and thus its clinical relevance to type 2 diabetes mellitus will undergo critical appraisal. Since all of these molecules have biological interactions with pancreatic islets, potential relationships may exist among them and they will also be discussed.