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This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/E569    most recent 90335.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Matveyenko, A. V. Articles by Butler, P. C. PubMed PubMed Citation Articles by Matveyenko, A. V. Articles by Butler, P. C.

Measurement of pulsatile insulin secretion in the rat: direct sampling from the hepatic portal vein

¹Larry L. Hillblom Islet Research Center, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California; and ²Endocrine Division, Mayo Medical and Graduate Schools of Medicine, Mayo Clinic, Rochester, Minnesota

Submitted 4 April 2008 ; accepted in final form 23 June 2008

It has previously been shown that insulin is secreted in discrete secretory bursts by sampling directly from the portal vein in the dog and humans. Deficient pulsatile insulin secretion is the basis for impaired insulin secretion in type 2 diabetes. However, while novel genetically modified disease models of diabetes are being developed in rodents, no validated method for quantifying pulsatile insulin secretion has been established for rodents. To address this we 1) developed a novel rat model with chronically implanted portal vein catheters, 2) established the parameters to permit deconvolution of portal vein insulin concentrations profiles to measure insulin secretion and resolve its pulsatile components, and 3) measured total and pulsatile insulin secretion compared with that in the dog, the species in which this sampling and deconvolution approach was validated for quantifying pulsatile insulin secretion. In rats, portal vein catheter patency and function were maintained for periods up to 2–3 wk with no postoperative complications such as catheter tract infection. Rat portal vein insulin concentration profiles in the fasting state revealed distinct insulin oscillations with a periodicity of 5 min and an amplitude of up to 600 pmol/l, which was remarkably similar to that in the dogs and in humans. Deconvolution analysis of portal vein insulin concentrations revealed that the majority of insulin (70%) in the rat is secreted in distinct insulin pulses occurring at 5-min intervals. This model therefore permits direct accurate measurments of pulsatile insulin secretion in a relatively inexpensive animal. With increased introduction of genetically modified rat models will be an important tool in elucidating the underlying mechanisms of impaired pulsatile insulin secretion in diabetes.

deconvolution; pulse mass

This article has been cited by other articles:

				A. V. Matveyenko, J. D. Veldhuis, and P. C. Butler Adaptations in pulsatile insulin secretion, hepatic insulin clearance, and {beta}-cell mass to age-related insulin resistance in rats Am J Physiol Endocrinol Metab, October 1, 2008; 295(4): E832 - E841. [Abstract] [Full Text] [PDF]