scholarly journals Stimulation of Adenylate Cyclase by Ca2+ and Calmodulin in Rat Islets of Langerhans: Explanation for the Glucose-induced Increase in Cyclic AMP Levels

Diabetes ◽  
1980 ◽  
Vol 29 (1) ◽  
pp. 74-77 ◽  
Author(s):  
G. W. G. Sharp ◽  
D. E. Wiedenkeller ◽  
D. Kaelin ◽  
E. G. Siegel ◽  
C. B. Wollheim
Diabetes ◽  
1980 ◽  
Vol 29 (1) ◽  
pp. 74-77 ◽  
Author(s):  
G. W. Sharp ◽  
D. E. Wiedenkeller ◽  
D. Kaelin ◽  
E. G. Siegel ◽  
C. B. Wollheim

1982 ◽  
Vol 2 (11) ◽  
pp. 867-876 ◽  
Author(s):  
I. Swenne

The regulatory role of cyclic AMP (cAMP) in the growth and insulin production of the islet organ in vitro has been investigated. The effects of dibutyryl cyclic AMP (dbcAMP), theophylline, and 3-isobutyl-1-methylxanthine (IBMX) on DNA replication and on the biosynthesis of RNA and insulin in fetal rat islets of Langerhans maintained in tissue culture have been studied. Raising the glucose concentration from 2.7 mM to 16.7 mM caused a two-fold increase in DNA replication. Both dbcAMP and theophylline markedly inhibited the DNA replication at all glucose Concentrations studied. Low concentrations of IBMX stimulated DNA synthesis. However, at higher concentrations of this drug, known to considerably increase the islet cAMP levels, a marked inhibition of islet DNA replication was observed. Both (pro)insulin and total protein biosynthesis were stimulated by glucose, whereas dbcAMP stimulated only the (pro)insulin biosynthesis. Since glucose is known to raise islet intracellular levels of cAMP, which is known to be an inhibitor of cellular proliferation, the observed glucose stimulation of both islet-cell DNA replication and insulin production appeared conflicting. It is suggested that this dual effect of glucose may depend on a stimulation of proliferation in a limited pool of islet cells which may not exhibit an increase in cAMP.


1976 ◽  
Vol 71 (3) ◽  
pp. 840-844 ◽  
Author(s):  
Nicholas Barden ◽  
Gabriel Alvarado-Urbina ◽  
Jean-Pierre Côté ◽  
André Dupont

1992 ◽  
Vol 12 (2) ◽  
pp. 95-100 ◽  
Author(s):  
Nicholas S. Berrow ◽  
Roger D. Hurst ◽  
Susan L. F. Chan ◽  
Noel G. Morgan

Rat islets express a pertussis toxin sensitive G-protein involved in receptor-mediated inhibition of insulin secretion. This has been assumed previously to represent “Gi” which couples inhibitory receptors to adenylate cyclase. Incubation of islet G-proteins with32P-NAD and pertussis toxin resulted in the labelling of a band of molecular weight 40,000. This band was very broad and did not allow resolution of individual components. Incubation of the radiolabelled proteins with an anti-Go antiserum resulted in specific immunoprecipitation of a32P-labelled band. These results demonstrate that the complement of pertussis toxin sensitive G-proteins in rat islets includes Go.


1986 ◽  
Vol 233 (1) ◽  
pp. 287-289 ◽  
Author(s):  
C S Hii ◽  
J Stutchfield ◽  
S L Howell

The phorbol ester 4 beta-phorbol 12-myristate 13-acetate (PMA), at concentrations of 0.1 microM and above, stimulated secretion of glucagon and of insulin from isolated rat islets of Langerhans incubated in the presence of 5.5 mM-glucose. Stimulation of secretion of both hormones by 1 microM-PMA persisted in the absence of external Ca2+, and could be abolished by incubating the islets at 4 degrees C. These findings suggest a role of protein kinase C in the alpha-cell (and beta-cell) secretory mechanism.


1985 ◽  
Vol 228 (3) ◽  
pp. 713-718 ◽  
Author(s):  
N G Morgan ◽  
G M Rumford ◽  
W Montague

Glucose (20 mM) and carbachol (1 mM) produced a rapid increase in [3H]inositol trisphosphate (InsP3) formation in isolated rat islets of Langerhans prelabelled with myo-[3H]inositol. The magnitude of the increase in InsP3 formation was similar when either agent was used alone and was additive when they were used together. In islets prelabelled with 45Ca2+ and treated with carbachol (1 mM), the rise in InsP3 correlated with a rapid, transient, release of 45Ca2+ from the cells, consistent with mobilization of 45Ca2+ from an intracellular pool. Under these conditions, however, insulin secretion was not increased. In contrast, islets prelabelled with 45Ca2+ and exposed to 20mM-glucose exhibited a delayed and decreased 45Ca2+ efflux, but released 7-8-fold more insulin than did those exposed to carbachol. Depletion of extracellular Ca2+ failed to modify the increase in InsP3 elicited by either glucose or carbachol, whereas it selectively inhibited the efflux of 45Ca2+ induced by glucose in preloaded islets. Under these conditions, however, glucose was still able to induce a small stimulation of the first phase of insulin secretion. These results demonstrate that polyphosphoinositide metabolism, Ca2+ mobilization and insulin release can all be dissociated in islet cells, and suggest that glucose and carbachol regulate these parameters by different mechanisms.


Sign in / Sign up

Export Citation Format

Share Document