Session: S06-Insulin Pulsatility Matters
Room 122 (Moscone Center)
The pancreatic islet shows extensive coupling between constituent cells which is important for the regulation of hormone secretion. Gap junction channels coordinate oscillations in intracellular free-calcium activity between β-cells in the islet. We have investigated the importance of these coordinated oscillations in individual islets to generate pulsatile insulin secretion and regulate glucose homeostasis. We have measured insulin dynamics in mice lacking islet gap junction coupling, using hyperglycemic clamps with rapid sampling of insulin. These mice are glucose intolerant, and show substantially diminished insulin pulse amplitudes. However the pulse timing is unchanged. Thus gap junctions in the islet regulate the in-vivo dynamics of insulin secretion, which in turn is important for glucose homeostasis. These dynamics are similarly disrupted in the early stages of type 2 diabetes, therefore dysregulation of islet gap-junction coupling could also be an important factor in the development of this disease.