Pulsatile insulin secretion accounts for 70% of total insulin secretion during fasting

Abstract

The purpose of the present study was to determine the contributions of discrete insulin secretory bursts vs. basal insulin release to total insulin secretion in vivo. Quantification of the partitioning of pulsatile and basal insulin secretion is complicated by physiological delivery of these pulses into the portal vein and the absence of validated methods of measuring the rates of pulsatile and basal insulin secretion in vivo. We therefore 1) developed a canine model with chronically implanted portal vein catheters, 2) validated an established deconvolution technique as well as a novel direct catheterization technique (Clustcath) for measurement of pulsatile and nonpulsatile insulin secretion rates in this model, and 3) applied these methods to study insulin secretion in the overnight-fasted dog in vivo to determine the contribution of pulsatile vs. basal insulin secretion to total rates of endogenous insulin secretion. Rates of total, pulsatile, and nonpulsatile endogenous insulin secretion measured by Cluscath closely parallel those measured by deconvolution analysis (54 +/- 15 vs. 51 +/- 11, 38 +/- 12 vs. 36 +/- 11, and 16 +/- 4 vs. 14 +/- 4 pmol/min, respectively). Clustcath and deconvolution indicated that the majority of insulin was secreted as pulses (70 +/- 6 and 66 +/- 7%, respectively). These data infer that any process that selectively decreases the pulsatile component of insulin secretion (e.g., diabetes mellitus) will likely have a major impact on total insulin secretion.

The conscious Göttingen minipig as a model for studying rapid pulsatile insulin secretion in vivo

“…Both inspection and deconvolution of data show a highly dynamic pulsatile insulin secretion that, in terms of frequency, is similar to what has been reported in humans and dogs [24,45]. The estimated periodicity of the pulsatile pattern depends on the analytical tool used.…”

“…Several animal models, including the rat [23], dog [24] and baboon [25], have been used to investigate insulin pulsatility. Although it is probably not possible to define one single optimal model in this field of research, the characteristics of the Göttingen minipig makes this species very relevant.…”

“…Apart from these characteristics, the animal model should show patterns of pulsatility similar to what is seen in humans, both in the basal state and in response to the recently introduced glucose pulse entrainment method [22]. Several animal models have been used to study pulsatile insulin secretion, including the rat [23], dog [24] and baboon [2,25]. Different experimental set-ups might require different properties of the model to be used.…”

Glucose and Insulin Synergistically Activate Phosphatidylinositol 3-Kinase to Trigger Oscillations of Phosphatidylinositol 3,4,5-Trisphosphate in β-Cells

“…Insulin released from the pancreas (33) and from individual islets is pulsatile (2). Measurements of [Ca 2ϩ ] i (34) and of Zn 2ϩ co-released from the insulin secretory granules (35) indicate that isolated ␤-cells also show pulsatile secretory activity.…”

Oscillatory control of insulin secretion

“…The oscillations are most prominent in the portal vein, which delivers blood from the pancreas to the liver. Measurements in the portal vein of dogs and humans have indicated that virtually all insulin (>70-75%) is released in a pulsatile fashion (Pørksen et al, 1995;Pørksen et al, 1997). Early estimates of pulse intervals are somewhat variable due to technical limitations but later data indicate a periodicity of 4-6 min in humans (Storch et al, 1993;Pørksen et al, 1997;Ritzel et al, 2001) and dogs (Pørksen et al, 1996).…”