In vitro exhaustion of pancreatic beta-cells.
To learn more about possible limited beta-cell secretory capacity and factors essential for insulin release, a perifusion system was applied that allowed the in vitro study of insulin secretion from isolated pancreatic islets for more than 6 h. Islets isolated from rats were stimulated with various glucose concentrations (7.5, 16.7, and 30 mM), alpha-ketoisocaproate (30 mM), and 30 mM glucose plus 1 mM 3-isobutyl-1-methylxanthine for several hours in Krebs-Ringer-bicarbonate buffer (KRB) or RPMI 1640. Islets showed "exhaustion" with all stimulatory conditions used when KRB was the perifusion medium. This was not prevented by addition of amino acids, phosphate, myo-inositol or arachidonic acid. With RPMI 1640 as the basal medium, exhaustion was not seen at 7.5 mM but was readily approached at higher glucose concentrations. It is possible that the exhaustion phenomenon observed here is due to a depletion of a readily releasable insulin pool.
M
M
Hoenig
L C
LC
MacGregor
F M
FM
Matschinsky
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002021:Buffers; D003470:Culture Media; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007294:Inositol / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000596:Amino Acids; D001095:Arachidonic Acids; D002021:Buffers; D003470:Culture Media; D007328:Insulin; D007651:Keto Acids; D016718:Arachidonic Acid; D007294:Inositol; C013082:alpha-ketoisocaproic acid; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine