Paracrine and autocrine control of insulin secretion in human islets: evidence and pending questions

Insulin secretion by li-cells is largely controlled by circulating nutrients, hormones, and neurotransmitters. However, recent years have witnessed the multiplication of studies investigating whether local regulation also takes place within pancreatic islets, in which li-cells cohabit with several other cell types. The cell composition and architectural organization of human islets differ from those of rodent islets and are particularly favorable to cellular interactions. An impressive number of hormonal (glucagon, glucagon-like peptide-1, somatostatin, etc.) and nonhormonal products (ATP, acetylcholine, y-aminobutyric acid, dopamine, etc.) are released by islet cells and have been implicated in a local control of insulin secretion. This review analyzes reports directly testing paracrine and autocrine control of insulin secretion in isolated human islets. Many of these studies were designed on background information collected in rodent islets. However, the perspective of the review is not to highlight species similarities or specificities but to contrast established and speculative mechanisms in human islets. It will be shown that the current evidence is convincing only for a minority of candidates for a paracrine function whereas arguments supporting a physiological role of others do not stand up to scrutiny. Several pending questions await further investigation.

Automated summary

Insulin secretion by li-cells in human pancreatic islets is influenced not only by circulating nutrients, hormones, and neurotransmitters, but also by local regulation within the islets, characterized by a unique cell composition and architectural organization. While some candidates for paracrine control of insulin secretion in human islets have strong evidence, others require further investigation to confirm their physiological role.