Faculty Collaboration Database

Glucose-induced insulin secretion from purified beta-cells. A role for modulation of Ca2+ influx by cAMP- and protein kinase C-dependent signal transduction pathways. J Biol Chem 1993 Apr 15;268(11):7785-91

Date

04/15/1993

Pubmed ID

8385120

DOI

10.1016/s0021-9258(18)53027-1

Scopus ID

2-s2.0-0027418326 (requires institutional sign-in at Scopus site)   57 Citations

Abstract

The effects of activation of cAMP- and protein kinase C-dependent signal transduction pathways were investigated on intracellular Ca2+ concentration ([Ca2+]i), cAMP content and insulin secretion from beta-cells purified by fluorescence-activated cell sorting from normal rat islets. The secretion of insulin from suspensions of purified beta-cells was dependent on glucose concentration and hormonal signals, including cAMP and activators of protein kinase C. Microfluorimetric measurement of [Ca2+]i with the fluorescent Ca2+ indicator fura-2 indicated that beta-cells differed immensely in their individual responsiveness to glucose stimulation. An increase in [Ca2+]i occurred in approximately 70% of beta-cells, whereas approximately 30% of beta-cells were nonresponsive to a glucose stimulus. Elevation of cAMP levels by theophylline or glucagon transformed nonresponsive beta-cells into cells which displayed marked increases in [Ca2+]i, and beta-cells which exhibited glucose-induced changes in [Ca2+]i showed further increases in [Ca2+]i and in the amplitude of Ca2+ oscillations. Carbachol and 12-O-tetradecanoylphorbol-13-acetate, activators of protein kinase C, did not induce any alterations in intracellular cAMP levels; nonetheless, these agents increased both the number of beta-cells which exhibited glucose-induced changes in [Ca2+]i and the amplitude of oscillations. The ability of cAMP or activators of protein kinase C to increase [Ca2+]i in single beta-cells was directly correlated with the ability of beta-cell suspensions to secrete insulin in response to a glucose stimulus. These results suggest that both cAMP- and protein kinase C-dependent pathways may regulate Ca2+ entry into beta-cells, possibly via voltage-dependent Ca2+ channels. Thus, this may represent a common mechanism whereby these different signal transduction pathways potentiate glucose-induced insulin secretion from beta-cells.

Author List

Wang JL, Corbett JA, Marshall CA, McDaniel ML

Author

John A. Corbett PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Calcium
Carbachol
Cells, Cultured
Cyclic AMP
Glucagon
Glucose
Insulin
Islets of Langerhans
Kinetics
Male
Protein Kinase C
Rats
Rats, Sprague-Dawley
Signal Transduction
Tetradecanoylphorbol Acetate
Theophylline
Time Factors