Inhibition of protein kinase A-induced glucagon synthesis and secretion by glucose.
The control of glucagon biosynthesis and secretion in the pancreatic islet was examined in response to protein kinase A stimulation at various glucose concentrations. Forskolin plus 3-isobutyl 1-methylxanthine (IBMX) stimulated both glucagon synthesis and secretion at a glucose concentration equivalent to hypoglycemia (0.5 g/L, P<.001), but not at higher glucose concentrations (1.0, 2.0, and 4.0 g/L, P>.05). Destruction of B cells with streptozotocin or inhibition of glycolysis with mannoheptulose did not reverse the inhibitory action of high glucose (4.0 g/L) on the response of glucagon to forskolin plus IBMX. In contrast, citrate but not EGTA treatment permitted forskolin plus IBMX to stimulate glucagon synthesis and secretion (P<.05 and P<.001, respectively) in the presence of high glucose. We conclude that citrate can block the inhibitory action of glucose on the response of A cells to the protein kinase A pathway, possibly through its effects on an intracellular metabolic pathway.
Stobie-Hayes
K M
KM
Department of Physiology, University of Toronto, Ontario, Canada.
Brubaker
P L
PL
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D005934:Glucagon / Q000096:biosynthesis* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D008297:Male; D051381:Rats; D013311:Streptozocin / Q000494:pharmacology
D002951:Citrates; D005576:Colforsin; D019343:Citric Acid; D013311:Streptozocin; D005934:Glucagon; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine