Exocrine and Endocrine Interactions in Cystic Fibrosis: A Potential Key to Understanding Insulin Secretion in Health and Disease?

The study of β-cell function in vivo has been hampered by the relative inaccessibility of the pancreas as well as the hybrid exocrine/endocrine nature of the organ. This has limited the ability to correlate structure with function, although some efforts have been made in this regard (1,2). Moreover, there are no tests available that can easily, accurately, and reproducibly measure β-cell secretion in a way that might be clinically relevant or influence therapeutic decisions for individual patients (3). The issue is further compounded by the conflation of β-cell function with β-cell mass, where the former can be taken to represent response to a “physiological” challenge and the latter is represented by the (presumed) maximal response to a “supra-physiological” challenge (4). How these relate to the numbers of functional islets or to islet “health” and integrity remains unknown, despite numerous efforts to image β-cell mass in vivo. Unfortunately in a time when an echocardiogram is routinely used for the assessment of cardiac structure and function, diabetologists are stuck with the equivalent of Laennec’s stethoscope.The response to a meal is affected by multiple factors (Fig. 1), including gastric accommodation, gastric trituration of complex food, intraluminal digestion, and subsequent absorption (5–8). In addition, the prevailing degree of insulin action will also alter β-cell secretion; indeed for glucose tolerance to be maintained, β-cell function must be able to compensate for impaired insulin action (4). This concept is embodied in the disposition index, which describes the hyperbolic relationship between the two parameters (9) (Fig. 1). Examination of insulin secretion in disease states where these parameters are directly or indirectly affected by the disease process …