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Synchronous Fluctuations of Blood Insulin and Lactate Concentrations in Humans¹

Divisions of Pediatric (R.F., M.S., O.M., F.S.) and Clinical Nephrology (E.R.), Ruperto-Carolus University, 69120 Heidelberg, Germany; and Department of Internal Medicine (J.D.V.), University of Virginia Health Sciences Center and National Science Foundation Center for Biological Timing, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Franz Schaefer, M.D., Pediatric Nephrology Division, Im Neuenheimer Feld 150, 69120 Heidelberg, Germany. E-mail: franz_schaefer{at}ukl.uniheidelberg.de

Oscillatory organization is a universal mode of signal transduction in living organisms. In vitro studies suggest spontaneous pulsatile fluctuations of intracellular energy metabolism. It is possible that, in vivo, some of these processes are synchronized by the pulsatile release of insulin. We assessed a potential coupling among plasma insulin, glucose, and lactate concentrations, by frequent blood sampling for 24 h in 11 healthy volunteers. Insulin sensitivity was assessed using the euglycemic hyperinsulinemic clamp technique. Lactate concentrations exhibited pulsatile fluctuations at an average interval of 84 ± 11 min, whereas sodium and pH were nonpulsatile. The lactate concentration pulses closely corresponded to insulin oscillations, which occurred with a periodicity of 86 ± 11 min. Blood glucose also fluctuated during daytime at an interval of 89 ± 32 min. During nighttime, the frequency and amplitude of glucose oscillations were lower. The daytime profiles showed significant temporal coupling and pattern synchrony among insulin, lactate, and glucose. Only the close temporal relationship between insulin and lactate release persisted during nighttime. The temporal coupling and pattern synchrony between insulin and lactate were correlated inversely with insulin sensitivity, and positively with the degree of abdominal obesity. Our results suggest that: 1) the concentration of lactate, an indicator of cellular energy metabolism, fluctuates periodically in vivo; 2) the lactate concentrations fluctuate in synchrony with insulin pulses; and 3) such coupling is more pronounced in obese, insulin-resistant individuals.

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