2005
DOI: 10.2337/diabetes.54.6.1649
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Pulsatile Insulin Secretion Dictates Systemic Insulin Delivery by Regulating Hepatic Insulin Extraction In Humans

Abstract: In health, insulin is secreted in discrete pulses into the portal vein, and the regulation of the rate of insulin secretion is accomplished by modulation of insulin pulse mass. Several lines of evidence suggest that the pattern of insulin delivery by the pancreas determines hepatic insulin clearance. In previous large animal studies, the amplitude of insulin pulses was related to the extent of insulin clearance. In humans (and in large animals), the amplitude of insulin oscillations is ϳ100-fold higher in the … Show more

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Cited by 208 publications
(204 citation statements)
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References 53 publications
(72 reference statements)
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“…For example, the amplitude of the resulting insulin oscillations in the portal vein is ϳ1,000 pmol/l in the basal state increasing to ϳ4,000 pmol/l after meal ingestion (15). The profile of this insulin concentration wavefront dictates the extent of hepatic insulin clearance in as much as the former is more effective than continuous insulin delivery in suppressing hepatic glucose output (10,16,17). Insulin signaling and insulin extraction by the liver may be optimized by a pulsatile mode of delivery.…”
mentioning
confidence: 99%
“…For example, the amplitude of the resulting insulin oscillations in the portal vein is ϳ1,000 pmol/l in the basal state increasing to ϳ4,000 pmol/l after meal ingestion (15). The profile of this insulin concentration wavefront dictates the extent of hepatic insulin clearance in as much as the former is more effective than continuous insulin delivery in suppressing hepatic glucose output (10,16,17). Insulin signaling and insulin extraction by the liver may be optimized by a pulsatile mode of delivery.…”
mentioning
confidence: 99%
“…Pioneering studies of yeast metabolism performed by Betz and Chance (10) led to the discovery that slow oscillations are generated by glycolytic phosphofructokinase-1 (PFK1) 2 via the autocatalytic activation of the enzyme by its product, fructose 1,6-bisphosphate (FBP) (11,12). Several studies suggest that this mechanism, which is also present in muscle (13)(14)(15), may also be operational in the ␤-cell (16).…”
mentioning
confidence: 99%
“…However, this simplicity means that the derived metric is not representative of insulin mediated glucose disposal in a dynamic, non-fasting situation. The pulsatile nature of insulin secretion [31,35] and lag in the insulinglucose dynamics cause effectively random errors in the derived HOMA metric. The relatively poor correlation of HOMA to the euglycaemic clamp SI metric (ISI G ) (R=-0.37) found in this study emphasises the uncertainty created by these fluctuations.…”
Section: Comparison To Other Testsmentioning
confidence: 99%
“…This process can be continued until convergence is reached. In contrast to the methods presented for the fully sampled DIST test pilot study [24] the first pass extraction parameter x L is fixed at a population average value of 0.7 [31][32][33].…”
Section: To Determine a New I(t) And Q(t) (I New (T) And Q New (T))mentioning
confidence: 99%