Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance and β-cell dysfunction. This review focuses on the β-cell, what defects occur when and why. Two major anatomic observations have been made in NIDDM. The β-cell mass is mildly reduced, especially when obesity is taken into account. Also, amyloid deposits are frequently observed in the islets. It is unclear whether these changes are genetically mediated or result secondary to the loss of glucose homeostasis. Many studies have looked at some aspect of insulin secretion in NIDDM, and two types of distinct abnormalities have been described. Early on, there is a marked disruption in pulsatile insulin delivery, which is potentially an important contributor to the insulin resistance. It is unclear whether the loss of pulsatile delivery is acquired or genetically induced. Later, after glucose intolerance has started, several other secretory abnormalities develop coincident with loss of β-cell glucorecognition. The net result is further deterioration in timing of insulin delivery and postprandial hyperglycemia. A second important consequence of the glucose blindness is that the inherent compensatory β-cell mechanisms that guard against hyperglycemia are bypassed. We propose that the loss of glucose responsiveness is a direct result of an elevated glucose concentration (socalled glucotoxicity) and have generated substantial data in rat models that support this idea. The logical conclusion is that β-cell function in NIDDM can be maximized by achieving the best metabolic control possible.

This content is only available via PDF.