β → α → δ Pancreatic Islet Cellular Perfusion in Dogs

Abstract

Intraislet communication between β-, α-, and δ-cells and their secretory products may theoretically occur via the paracrine (interstitial) and/or vascular routes. Recently, we have shown that there is a directed microvascular circulation in the rat islet with a cellular order of perfusion of β → α → δ. The direction of microvascular perfusion of cells within the dog islet has been controversial. Anterograde (arterial) perfusion and retrograde (reversed or venous) perfusion of a segment of isolated dog pancreas with potent insulin antibodies yielded results similar to those found in the rat pancreas (anterograde, 158 ±44% increase in glucagon and 65 ± 20% increase in somatostatin; retrograde, no change in glucagon or somatostatin). Anterograde infusion of glucagon antibody (no change in insulin, −33.5 ± 3% decrease in somatostatin) or somatostatin antibody (no change in insulin or glucagon) also yielded the same results as in the rat pancreas. Anterograde infusion of 500 pg/ml glucagon caused a larger increase in insulin secretion (245 ± 10%) than retrograde infusion (45 ± 4%), whereas somatostatin was stimulated more retrogradely (339 ± 17%) than anterogradely (121 ± 9%). Anterograde infusion of somatostatin produced a larger decrease in insulin and glucagon than did retrograde perfusion (P < .0001 for both comparisons). The retrograde infusion of 0.3 mU/ml insulin caused a decrease in glucagon but was without effect anterogradely. The results from the infusion of exogenous hormones suggest that the sensitivity of the α-, β-, and δ-cells to insulin, glucagon, and somatostatin is determined by the β → α → δ order of perfusion. The antibody studies indicate that directed microvascular perfusion is central to intraislet regulation of insular secretions in dogs.