Synchronous Fluctuations of Blood Insulin and Lactate Concentrations in Humans¹

Abstract

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.

Determination of Glucose Levels Using a Functionalized Hydrogel−Optical Fiber Biosensor: Toward Continuous Monitoring of Blood Glucose in Vivo

“…In comparison to the control experiment, there is a loss in sensitivity of ∼4% with 1 mM lactate present, whereas at 5 mM, the sensitivity is reduced by ∼17%. The ambient level of lactate in humans is approximately 1 mM, , although it can rise to much higher levels, for example, during exercise . The pH of the solution was measured independently, which remained constant when 5 mM lactate was added.…”

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“…The lactate then enters the liver through the bloodstream in the so-called “indirect pathway” 26 27 . Lac rest is also physiologically linked to the diurnal blood glucose and insulin levels 28 . However, this relation is affected by metabolic disease which might lead to a higher basal lactate production of adipocytes but also deteriorate the capacity of adipocytes to provide lactate in response to glucose ingestion as part of this “indirect pathway” 29 .…”

“…Unauthorized distribution is strictly prohibited. [28]. However, this relation is affected by metabolic disease which might lead to a higher basal lactate production of adipocytes but also deteriorate the capacity of adipocytes to provide lactate in response to glucose ingestion as part of this "indirect pathway" [29].…”

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“…Not only are there synthetic compounds which may show such properties, but also natural compounds, e.g. Δ8,9-dehydroestrone sulphate, one of the constituents of conjugated equine oestrogens [14]. Tissue selectivity for some compounds may also result from the differential effects of their metabolites, e.g.…”