Phosphorylated inositol compounds in beta -cell stimulus-response coupling.
Pancreatic beta-cell function is essential for the regulation of glucose homeostasis in humans, and its impairment leads to the development of type 2 diabetes. Inputs from glucose and cell surface receptors act together to initiate the beta-cell stimulus-response coupling that ultimately leads to the release of insulin. Phosphorylated inositol compounds have recently emerged as key players at all levels of the stimulus-secretion coupling process. In this current review, we seek to highlight recent advances in beta-cell phosphoinositide research by dividing our examination into two sections. The first involves the events that lead to insulin secretion. This includes both new roles for inositol polyphosphates, particularly inositol hexakisphosphate, and both conventional and 3-phosphorylated inositol lipids. In the second section, we deal with the more novel concept of the autocrine role of insulin. Here, released insulin initiates signal transduction cascades, principally through the activity of phosphatidylinositol 3-kinase. This new round of signal transduction has been established to activate key beta-cell genes, particularly the insulin gene itself. More controversially, this insulin feedback has also been suggested to either terminate or enhance insulin secretion events.
Barker
Christopher J
CJ
Department of Molecular Medicine, The Rolf Luft Center for Diabetes Research, Karolinska Institutet, S-171 76 Stockholm, Sweden.
Leibiger
Ingo B
IB
Leibiger
Barbara
B
Berggren
Per-Olof
PO
D000818:Animals; D019898:Autocrine Communication; D025461:Feedback, Physiological; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D050356:Lipid Metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D007295:Inositol Phosphates; D007328:Insulin; D011956:Receptors, Cell Surface; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose