Dynamics of Insulin Release and Microtubular-Microfilamentous System. I. EFFECT OF CYTOCHALASIN B

Abstract

A B S T R A C T In order to assess the participation of the microfilamentous cell web in the multiphasic response of the pancreatic beta cell, the effect of cytochalasin B upon both glucose-and sulfonylurea-induced insulin release was investigated in the perfused isolated pancreas. Cytochalasin B failed to affect the basal rate of insulin release, but enhanced the initial and later phases of insulin secretion in response to either glucose or gliclazide. In addition, cytochalasin B lowered the threshold concentration for the stimulant action of glucose upon insulin release. Ultrastructural studies supported the concept of a specific interaction of cytochalasin B with the microfilamentous cell web of the beta cell. It is concluded that the integrity of such a structure is equally important for both the initial and later secretory responses of the beta cell to various insulinotropic agents.

The stimulus-secretion coupling of glucose-induced insulin release. Metabolic and functional effects of NH4+ in rat islets.

“…Indeed, on one hand, NH4+ failed to affect the ability of cytochalasin B to augment glucose-stimulated insulin release (Table II). The latter effect if currently ascribed to the interference of cytochalasin B with the microfilamentous cell web known to control the final access of secretory granules to the plasma membrane (15). On the other hand, and in contrast to what is observed with poisons of the pancreatic ,-cell microtubularmicrofilamentous system, NH4+ did not modify the normal relationship between 45Ca2+ net uptake and insulin release (Fig.…”

“…Pancreases removed from fed rats were placed in an open circuit extracorporeal perfusion unit, as described elsewhere (15). The perfusate contained 5 mg/ml albumin and 40 mg/ml dextran; as previously outlined (16).…”

Actin Dynamics Regulated by the Balance of Neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) and Cofilin Activities Determines the Biphasic Response of Glucose-induced Insulin Secretion

“…This may account for the characteristic dynamics of first phase of GIIS, which occurs rapidly, massively, and transiently. Indeed, actin-depolymerizing agents such as cytochalasin B and latrunculin B sustain massive insulin secretion from perifused pancreatic islets during application (23,45,57). It is also established that insulin is immediately, massively, and transiently secreted by K ϩ stimulation (6,8).…”

Metabolic amplifying pathway increases both phases of insulin secretion independently of β-cell actin microfilaments

“…Early electron microscopic studies (45) have shown that cytochalasin B (20 M) disrupts the web of microfilaments underneath the plasma membrane in rat ␤-cells. More recent morphological and biochemical approaches have established that latrunculin B (10 M) decreases actin polymerization (17,43,44), whereas jasplakinolide (5 M) increases actin polymerization (28) in MIN6 insulin-secreting cells.…”

“…Pioneer studies by Lacy et al (20) and VanObberghen et al (45) showed that cytochalasins, which depolymerize filamentous actin, facilitate insulin secretion and prompted the suggestion that this filamentous web actually limits access of granules to the exocytotic sites. Extending early models (24,46), more recent work (9,47,50) using single ␤-cells or insulin-secreting cell lines has proposed that granule translocation along actin filaments or remodeling of the web of actin filaments is involved in the replenishment of releasable granular pools, raising the possibility that these events contribute to the amplifying action of glucose.…”