Glucose‐induced cAMP elevation in β‐cells involves amplification of constitutive and glucagon‐activated GLP‐1 receptor signalling

SummaryTiclopidine and its potent analogue, clopidogrel, are powerful inhibitors of ADP-induced platelet aggregation. In order to improve the understanding of this ADP-selectivity, we studied the effect of these compounds on PGE1-stimulated adenylate cyclase and on the inhibition of this enzyme by ADP, epinephrine and thrombin. Neither drug changed the basal cAMP levels nor the kinetics of cAMP accumulation upon PGEj-stimulation in rat or rabbit platelets, which excludes any direct effect on adenylate cyclase or on cyclic nucleotide phosphodiesterase. However, the drop in cAMP levels observed after addition of ADP to PGEr stimulated control platelets was inhibited in platelets from treated animals. In contrast, the drop in cAMP levels produced by epinephrine was not prevented by either drug in rabbit platelets. In rat platelets, thrombin inhibited the PGEX-induced cAMP elevation but this effect seems to be entirely mediated by the released ADP. Under these conditions, it was not surprising to find that clopidogrel also potently inhibited that effect of thrombin on platelet adenylate cyclase. In conclusion, ticlopidine and clopidogrel selectively neutralize the ADP inhibition of PGEr activated platelet adenylate cyclase in rats and rabbits.

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MICROCHEMICAL ASSAYS OF GLUCOSE AND GLUCOSE-6-PHOSPHATE IN MAMMALIAN PANCREATIC β-CELLS

Acta Endocrinologica ◽

10.1530/acta.0.0590479 ◽

1968 ◽

Vol 59 (3) ◽

pp. 479-486 ◽

Cited By ~ 12

Author(s):

Lars-Ake Idahl ◽

Bo Hellman

Keyword(s):

Glucose Level ◽

Exocrine Pancreas ◽

The Other ◽

Wide Concentration Range ◽

Β Cells ◽

Pancreatic Β Cells ◽

Enzymatic Cycling ◽

Glucose Diffusion ◽

Significant Barrier ◽

The Brain

ABSTRACT The combination of enzymatic cycling and fluorometry was used for measuring glucose and glucose-6-phosphate in pancreatic β-cells from obese-hyperglycaemic mice. The glucose level of the β-cells corresponded to that of serum over a wide concentration range. In the exocrine pancreas, on the other hand, a significant barrier to glucose diffusion across the cell membranes was demonstrated. During 5 min of ischaemia, the glucose level remained practically unchanged in the β-cells while it increased in the liver and decreased in the brain. The observation that the pancreatic β-cells are characterized by a relatively low ratio of glucose-6-phosphate to glucose may be attributed to the presence of a specific glucose-6-phosphatase.

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IONIC EFFECTS ON THE UPTAKE OF CHLOROMERCURIBENZENE-p-SULPHONIC ACID BY PANCREATIC ISLETS

Acta Endocrinologica ◽

10.1530/acta.0.0860552 ◽

1977 ◽

Vol 86 (3) ◽

pp. 552-560 ◽

Cited By ~ 3

Author(s):

Monica Söderberg ◽

Inge-Bert Täljedal

Keyword(s):

Pancreatic Islets ◽

Islet Cell ◽

Choline Chloride ◽

Inorganic Ions ◽

Sulphonic Acid ◽

Cell Uptake ◽

Β Cells ◽

Sulphydryl Groups ◽

Microdissected Pancreatic Islets ◽

Ionic Effects

ABSTRACT Effects of inorganic ions on the uptake of chloromercuribenzene-p-sulphonic acid (CMBS) were studied in microdissected pancreatic islets of non-inbred ob/ob-mice. Na2SO4 stimulated the total islet cell uptake of CMBS but decreased the amount of CMBS remaining in islets after brief washing with L-cysteine. CaCl2 stimulated both the total and the cysteine-non-displaceable uptake; the stimulatory effect of CaCl2 on the cysteine-non-displaceable CMBS uptake was counteracted by Na2SO4. NaCl, KCl or choline chloride had no significant effect on the total islet cell uptake of CMBS, whereas LiCl was stimulatory. It is concluded that β-cells resemble erythrocytes in having a permeation path for CMBS that is inhibited by SO42−. By analogy with existing models of the erythrocyte membrane, it is suggested that the SO42−-sensitive path leads to sulphydryl groups controlling monovalent cationic permeability in β-cells.

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