Ionic, electrical, and secretory effects of protein kinase C activation in mouse pancreatic B-cells: studies with a phorbol ester

Journal Article · Tue Sep 01 04:00:00 EDT 1987 · Endocrinology; (United States)

DOI:https://doi.org/10.1210/endo-121-3-1025· OSTI ID:6062130

Bozem, M; Nenquin, M; Henquin, J C

The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was used to study the effects of protein kinase C activation on stimulus-secretion coupling in mouse pancreatic B-cells. At a nonstimulatory concentration of glucose (3 mM), 100 nM TPA, but not 10 nM TPA, slightly and slowly increased insulin release and /sup 45/Ca/sup 2 +/ efflux and decreased /sup 86/Rb/sup +/ efflux, but did not affect the membrane potential of B-cells. At a threshold concentration of glucose (7 mM), 100 nM TPA markedly increased insulin release without triggering electrical activity in B-cells. At a stimulatory concentration of glucose (10 mM), TPA caused a dose-dependent irreversible increase in insulin release, /sup 45/Ca/sup 2 +/ efflux, and /sup 86/Rb/sup +/ efflux and slightly augmented islet cAMP levels. Omission of extracellular Ca/sup 2 +/ abolished the effects of 10 nM TPA and partially inhibited those of 100 nM TPA on insulin release and /sup 45/Ca/sup 2 +/ efflux. In contrast, their effect on /sup 86/Rb/sup +/ efflux was paradoxically augmented. Glucose-induced electrical activity in B-cells was only marginally affected by TPA; the duration of the slow waves with spikes was not modified, but a small shortening of the polarized intervals raised their frequency and slightly increased the overall activity. This increase was significant only with 10 nM TPA, whereas only 100 nM TPA brought about a minute increase in /sup 45/Ca/sup 2 +/ influx. These results thus show that TPA induces insulin release or potentiates glucose-induced insulin release without mimicking or amplifying the initial ionic and electrical signals triggered by glucose. They suggest that protein kinase C activation affects stimulus-secretion coupling by modulating intracellular and/or nonelectrogenic membrane events.

• Research Organization: Univ. of Saarland, Homburg/Saar, West Germany
• OSTI ID: 6062130
• Journal Information: Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 121:3; ISSN ENDOA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALDEHYDES
ALKALI METAL COMPOUNDS
ALKALI METAL ISOTOPES
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
AMP
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CALCIUM 45
CALCIUM COMPOUNDS
CALCIUM ISOTOPES
CARBOHYDRATES
CARCINOGENS
CATIONS
CELL CONSTITUENTS
CELL MEMBRANES
CHARGED PARTICLES
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DOSE-RESPONSE RELATIONSHIPS
ELECTROPHYSIOLOGY
ENDOCRINE GLANDS
ENZYME ACTIVITY
ENZYMES
ESTERS
EVEN-ODD NUCLEI
GLANDS
GLUCOSE
HEXOSES
HORMONES
INSULIN
INTERMEDIATE MASS NUCLEI
IONS
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MATERIALS
MEMBRANE TRANSPORT
MEMBRANES
MICE
MINUTES LIVING RADIOISOTOPES
MONOSACCHARIDES
NUCLEI
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PANCREAS
PEPTIDE HORMONES
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PHYSIOLOGY
RADIOISOTOPES
RODENTS
RUBIDIUM 86
RUBIDIUM COMPOUNDS
RUBIDIUM ISOTOPES
SACCHARIDES
SECRETION
SOMATIC CELLS
TRACER TECHNIQUES
TRANSFERASES
VERTEBRATES