Ion Channels and Regulation of Insulin Secretion in Beta-Cells

After eating a meal high in carbohydrates, beta cells in the islets of Langerhans of the pancreas secrete insulin in response to the metabolic fuels and neurohormonal inputs they receive. Insulin secretion must be kept under tight control in order to keep glucose levels from fluctuating. For example, the pathophysiology of type 2 diabetes is driven by a decline in insulin production, either absolute or relative, in the presence of insulin resistance.

The mechanism that underlies how glucose increases the release of insulin has, for the most part, remained unaltered ever since it was discovered more than three decades ago. In reaction to glucose, the ratio of ATP to ADP that is found inside the cell rises, which causes the ATP-sensitive potassium (K_ATP) ion channels to close. These channels are the target of the medications known as sulfonylureas. As a consequence of this, the beta-cell membrane becomes depolarized, action potentials are induced, voltage-gated calcium ion channels are activated, and the amount of calcium ion that is present inside the cell rises, which ultimately leads to the exocytosis of insulin.

The functions and molecular identities of the various significant channels that determine the electrical response in these cells have only recently been fully elucidated. Despite the fact that a large number of additional ion channels are known to contribute to the excitability of beta cells, it was not until recently that this information became available.