Walter S. Zawalich, Marc Bonnet-Eymard, and Kathleen C. Zawalich

Yale University School of Nursing, 100 Church Street South, New Haven, CT 06536-0740 USA

Received 2/24/97; Accepted 2/27/97; On-line 3/15/97

7. The beta cell, obesity and NIDDM

Before summation it is perhaps not unreasonable to place the basic science studies discussed above into some type of clinical perspective. The question might be posed as to how signaling in the PLC/PKC system may be involved in altered patterns of insulin secretion established to occur in both obesity and NIDDM. In obesity, ß-cell secretion is dramatically amplified. Thus, in both human obesity (92, 93) and in several well characterized animal models of obesity (94, 95), early and perhaps even primary changes in ß-cell sensitivity to stimulation have been observed. In fact, even in preobese mice, the sensitivity of their islets to agonists which increase information flow in the PLC/PKC signaling system is enhanced and contributes to the early and perhaps primary hyperinsulinemia in these animals (96). Since insulin resistance can be acquired as a consequence of hyperinsulinemia(97-99), changes at the level of ß-cell signal transduction systems which amplify their stimulatory effect on insulin release, may be primary etiologic components in the odyssey to obesity(100). Finally, while there is little doubt that ß-cell failure or decompensation is essential in the development of frank NIDDM, the nature of the biochemical lesion responsible for the reduction in insulin secretion is not known. However, since ß-cell failure to secrete enough insulin to maintain glucose homeostasis is a consequence of hyperglycemia(32) and since high glucose desensitizes the ß-cell by inhibiting PLC activation (33, 101), a reasonable suggestion is that the impaired activation of ß-cell PLC may precipitate NIDDM in some individuals.