AJP - Endocrinology and Metabolism, Vol 269, Issue 6 E1106-E1114, Copyright © 1995 by American Physiological Society

ARTICLES

Impact of sampling technique on appraisal of pulsatile insulin secretion by deconvolution and cluster analysis

N. Porksen, S. Munn, J. Steers, J. D. Veldhuis and P. C. Butler
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.

Little is known about the optimal experimental conditions for assessing pulsatile insulin secretion in vivo. To address this, we employed a recently validated canine model (n = 12) to determine the consequences of 1) sampling from the systemic circulation (SC) vs. the portal vein (PV), 2) sampling intensity and duration, and 3) deconvolution vs. cluster analysis on assessing pulsatile insulin secretion. PV vs. SC sampling resulted in a approximately 40% higher pulse frequency by deconvolution (9.0 +/- 0.5 vs. 6.6 +/- 0.9 pulses/h, P < 0.02) and cluster analysis (7.5 +/- 0.3 vs. 5.6 +/- 0.6 pulses/h, P < 0.01) due to a higher signal-to-noise ratio (19 +/- 4.8 PV vs. 12 +/- 1.8 SC). PV sampling also disclosed a higher calculated contribution of the pulsatile vs. nonpulsatile mode of delivery to total insulin secretion (57 +/- 4 vs. 28 +/- 5%, P < 0.001). Analysis of the relevance of sampling intensity revealed that 1-min data yielded a markedly higher estimate of pulse frequency with PV sampling than 2-min data (9.0 +/- 0.5 vs. 5.4 +/- 0.5, P < 0.02, deconvolution; 7.5 +/- 0.3 vs. 4.3 +/- 0.6 pulses/h, P < 0.001, cluster). Optimal sampling duration was shown to be 40 min or more. We conclude that the resolving power of the analytical tool, the anatomic site of blood withdrawal, the frequency of blood sampling, and the duration of the total observation interval all significantly influence estimated insulin secretory pulse frequency and the fraction of insulin secreted in pulses. With the assumption that PV 1-min insulin data constitute the "gold standard," our in vivo inferences of 7.5-9.0 insulin pulses/h closely recapitulate in vitro islet secretory activity.

This article has been cited by other articles:

				R. A. Ritzel, J. D. Veldhuis, and P. C. Butler The mass, but not the frequency, of insulin secretory bursts in isolated human islets is entrained by oscillatory glucose exposure Am J Physiol Endocrinol Metab, April 1, 2006; 290(4): E750 - E756. [Abstract] [Full Text] [PDF]

				N. Porksen, M. Hollingdal, C. Juhl, P. Butler, J. D. Veldhuis, and O. Schmitz Pulsatile Insulin Secretion: Detection, Regulation, and Role in Diabetes Diabetes, February 1, 2002; 51(90001): S245 - 254. [Abstract] [Full Text] [PDF]

				L. L. Kjems, B. M. Kirby, E. M. Welsh, J. D. Veldhuis, M. Straume, S. S. McIntyre, D. Yang, P. Lefebvre, and P. C. Butler Decrease in {beta}-Cell Mass Leads to Impaired Pulsatile Insulin Secretion, Reduced Postprandial Hepatic Insulin Clearance, and Relative Hyperglucagonemia in the Minipig Diabetes, September 1, 2001; 50(9): 2001 - 2012. [Abstract] [Full Text] [PDF]

				R. Ritzel, M. Schulte, N. Pørksen, M. S. Nauck, J. J. Holst, C. Juhl, W. März, O. Schmitz, W. H. Schmiegel, and M. A. Nauck Glucagon-Like Peptide 1 Increases Secretory Burst Mass of Pulsatile Insulin Secretion in Patients With Type 2 Diabetes and Impaired Glucose Tolerance Diabetes, April 1, 2001; 50(4): 776 - 784. [Abstract] [Full Text]

				T. Laedtke, L. Kjems, N. Porksen, O. Schmitz, J. Veldhuis, P. C. Kao, and P. C. Butler Overnight inhibition of insulin secretion restores pulsatility and proinsulin/insulin ratio in type 2 diabetes Am J Physiol Endocrinol Metab, September 1, 2000; 279(3): E520 - E528. [Abstract] [Full Text] [PDF]

				D. M. Keenan and J. D. Veldhuis Explicating hypergonadotropism in postmenopausal women: a statistical model Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2000; 278(5): R1247 - R1257. [Abstract] [Full Text] [PDF]

				C. B. Juhl, N. Porksen, J. Sturis, A. P. Hansen, J. D. Veldhuis, S. Pincus, M. Fineman, and O. Schmitz High-frequency oscillations in circulating amylin concentrations in healthy humans Am J Physiol Endocrinol Metab, March 1, 2000; 278(3): E484 - E490. [Abstract] [Full Text] [PDF]

				N. Porksen, B. Nyholm, J. D. Veldhuis, P. C. Butler, and O. Schmitz In humans at least 75% of insulin secretion arises from punctuated insulin secretory bursts Am J Physiol Endocrinol Metab, November 1, 1997; 273(5): E908 - E914. [Abstract] [Full Text] [PDF]