The physiological role of the β-cell insulin receptor is unknown. To evaluate a candidate function, the insulin regulation of fluid-phase pinocytosis was investigated in a clonal insulinoma cell line (βTC6-F7) and, for comparison, also in Chinese hamster ovary cells transfected with the human insulin receptor (CHO-T cells). In CHO-T cells, the net rate of fluid-phase pinocytosis was rapidly increased 3–4-fold over the basal rate by 100 nM insulin, with half-maximal stimulation at 2 nM insulin, as assayed by cellular uptake of horseradish peroxidase from the medium. Wortmannin, an inhibitor of phosphatidylinositol (PI)-3-kinase, blocked insulin-stimulated pinocytosis with an IC50 of 7.5 nM without affecting the basal rate of pinocytosis. In insulin-secreting βTC6-F7 cells, the secretagogues glucose and carbachol (at maximally effective concentrations of 15 mM and 0.5 mM respectively) augmented fluid-phase pinocytosis 1.65-fold over the basal rate. Wortmannin also inhibited secretagogue-stimulated pinocytosis in these β-cells with an IC50 of 7 nM but did not affect the basal rate of pinocytosis measured in the absence of secretagogues. Wortmannin did not influence either basal or secretagogue-induced insulin secretion. Although these βTC6-F7 cells have cell-surface insulin receptors, adding exogenous insulin or insulin-like growth factor 1 did not affect their rate of fluid-phase pinocytosis, either in the absence or presence of secretagogues. From these observations, we conclude that: (1) in both insulin-secreting β-cells and in conventional, insulin-responsive CHO-T cells, a common, wortmannin-sensitive reaction, which probably involves PI-3-kinase, regulates fluid-phase pinocytosis; (2) the insulin-receptor signal transduction pathway is dissociated from the regulation of fluid-phase pinocytosis in the insulin-secreting β-cell line we studied; and (3) the enhancement of fluid-phase pinocytosis associated with secretagogue-induced insulin release in βTC6-F7 cells is not attributable to autocrine activation of β-cell surface insulin receptors.
Skip Nav Destination
Article navigation
September 1996
-
Cover Image
Cover Image
- PDF Icon PDF LinkTable of Contents
Research Article|
September 01 1996
Insulin and secretagogues differentially regulate fluid-phase pinocytosis in insulin-secreting β-cells
Gang XU;
Gang XU
1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Room B-101, Richards Building, Philadelphia, PA 19104, U.S.A.
Search for other works by this author on:
Jennie HOWLAND;
Jennie HOWLAND
1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Room B-101, Richards Building, Philadelphia, PA 19104, U.S.A.
Search for other works by this author on:
Paul L ROTHENBERG
Paul L ROTHENBERG
*
1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Room B-101, Richards Building, Philadelphia, PA 19104, U.S.A.
*To whom correspondence should be addressed.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
February 19 1996
Revision Received:
May 10 1996
Accepted:
May 29 1996
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1996
1996
Biochem J (1996) 318 (2): 623–629.
Article history
Received:
February 19 1996
Revision Received:
May 10 1996
Accepted:
May 29 1996
Citation
Gang XU, Jennie HOWLAND, Paul L ROTHENBERG; Insulin and secretagogues differentially regulate fluid-phase pinocytosis in insulin-secreting β-cells. Biochem J 1 September 1996; 318 (2): 623–629. doi: https://doi.org/10.1042/bj3180623
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.