Greaterin Vivothan in Vitro Pulsatility of Insulin Secretion with Synchronized Insulin and Somatostatin Secretory Pulses

Abstract

To examine the control of pulsatile insulin secretion by an intrapancreatic pacemaker, samples at minute intervals were taken from the portal vein in dogs in vivo and from an isolated perfused pancreas preparation in vitro. Anesthetized dogs had high amplitude pulsatile insulin secretion which was not consistently regular. Fourier transform analysis showed dominant 20- and 10-min periods of spectral power (P less than 0.01). After vagotomy, the relative oscillatory power was reduced from 83% to 42%, about a lower mean concentration with abolition of the 20-min oscillations. The isolated perfused dog pancreas also had oscillatory insulin secretion with oscillatory power of 12%. Autocorrelation showed regularity of in vitro insulin secretion with a period of 10-11 min (P less than 0.0001). In addition, somatostatin was secreted from the in vitro pancreas in pulses in phase with insulin (cross-correlation P less than 0.0001). These data are in accord with the theory that the pancreas has an internal pacemaker which controls insulin secretion, and that the amplitude of the oscillations is modulated by vagal control. The pacing of the islets may be coordinated by a neural network, whereas coincident pulsatile somatostatin release may temporarily suppress islet secretion and help to synchronize hormonal oscillations.

The in vivo regulation of pulsatile insulin secretion

“…The high frequency sampling and replicate measurements are costly so sampling duration should be short. The repetitive nature of pulsatile insulin secretion [4,5,10,33,76] would allow a reliable measurement of pulse frequency and amplitude using a sampling duration of 40 to 60 min [69] if deconvolution analysis or simple pulse detection algorithms are used. However, analysis based on autocorrelation (minimum 2 times pulse interval) and on spectral analysis (n > 100) as well as regularity statistics (approximate entropy: n > 40) in general improve with increased sampling duration and therefore most studies using periodicity statistics are carried out over a longer duration [4,5,10,33,76].…”

“…However, the net contribution of the secretory bursts is important, because the presence of concentration oscillations does not exclude the dominance of a time-invariant (basal) release pattern. Furthermore, the relation between the in vivo observed secretory bursts and the in vitro observed pulsatile release from the isolated pancreas [9,10,101] and the isolated peri-perfused islets [102,103], as well as episodic beta-cell depolarization [104±106], beta-cell glycolysis [105,107], and beta-cell increase in calcium remains to be established [104, 105, 108±111]. The coupling of cyclic metabolism to pulsatile in vitro release has been addressed in an excellent review by Tornheim [112].…”

“…The pulsatile pattern of release seems to be important not only for insulin but also for the pituitary [100,153,154], adrenal [155] and parathyroid [156] hormones, for GLP-1 [157], leptin [158], and other islet hormones [4,6,9,10,84]. Because both growth hormone and the islet hormones are important for metabolic control, an interplay between the hormones might be necessary to optimize their release and action.…”

Oscillatory control of insulin secretion

“…Studies in normal subjects with suppressed endogenous insulin secretion and diabetic patients have indicated that less insulin is required to maintain normoglycaemia if the hormone is infused in an oscillatory manner compared to a constant rate (Matthews et al, 1983b;Bratusch-Marrain et al, 1986;Matthews et al, 1987;Paolisso et al, 1988a;Paolisso et al, 1988b). The better efficiency of oscillatory insulin delivery is probably due to higher expression of insulin receptors (Goodner et al, 1988).…”

Pulsatile Insulin Secretion: Detection, Regulation, and Role in Diabetes

“…Most studies are time and cost consuming, and the ideal sampling duration should be the shortest duration to give reliable data. With deconvolution analysis and pulse detection analysis, 40 -60 min (64) seems to result in good data whereas regularity statistics (autocorrelation [minimum two times pulse interval] and spectral analysis [N Ͼ100]) as well as regularity statistics (approximate entropy: N Ͼ40) improve with increased sampling duration (5,6,9,26,67). Insulin versus C-peptide measurements.…”