The Beta Cell and First-Phase Insulin Secretion

Introduction

The majority of type 2 diabetes results from the failure of the beta cell to augment insulin secretion in response to an increasing demand for insulin from peripheral tissues. In patients without insulin resistance, the beta cell fails to meet even the usual demand for insulin. In the treatment of type 2 diabetes, strategies in the "early" stage of disease focus on the insulin-sparing effects of lifestyle modification and oral agents, reducing the demand on residual beta-cell function. Therapies that augment endogenous insulin secretion are also utilized during this phase. Finally, more advanced diabetes requires insulin replacement therapy in recognition of progressive beta-cell failure.

In the spectrum of beta-cell dysfunction, however, even early diabetes represents a very advanced stage of beta-cell failure. At the time of diagnosis, a substantial percentage of beta-cell mass has been lost, and the remaining beta cells are dysfunctional, depleted of insulin-containing granules, and responding relatively poorly to glucose stimulation. First-phase insulin secretion, which is responsible for blunting the postprandial glycemic excursion, is virtually absent, and normal pulsatile insulin secretion is severely disordered.