Evidence for pancreatic pacemaker for insulin oscillations in low-frequency range.

Circulating insulin concentrations oscillate in regular fashion, with periods that fall into a high-frequency (period of 5-17 min) or low-frequency (period of 50-150 min) range. Only the high-frequency oscillations have so far been reported in vitro, suggesting that these derive from a primary pancreatic source. This study tested whether the low-frequency insulin oscillations could also be identified in vitro. Rat islets of Langerhans were perifused for 20 h using RPMI medium with 5.5 mM glucose. Perifusate fractions were collected at 9.9-min intervals. Mean insulin concentrations at the outset were 21.4 +/- 2.9 microU/ml, increased to 32.5 +/- 4.6 (P < 0.05) between 13 and 17 h after the start of perifusion, and then either leveled off or decreased to baseline. Superimposed on this general trend, we found sustained insulin oscillations with a period of 50-100 min. The mean amplitude was 14.2 +/- 4.2 microU/ml, and the amplitude/mean ratio was 64.6 +/- 12%. Spectral analysis revealed significant peaks at periods that were close to either 50 or 100 min and a smaller peak at 24-37 min. These data, using in vitro methodology and constant glucose concentrations, indicate the presence of sustained, spontaneous, low-frequency, ultradian insulin oscillations in the pancreatic islets. This provides evidence for a pancreatic component that may participate in the previously described in vivo ultradian insulin oscillations. This finding may also provide a mechanism for the apparent escape from glucose entrainment of serum insulin oscillations in non-insulin-dependent diabetes mellitus.