Glucose-Induced Time-Dependent Potentiation and “Run Down” of Insulin Secretion in Islets of Young Rats
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A “run down” phenomenon in isolated islets from young rats has been detected, in which the amount of insulin released in response to glucose decreases with time. This has been studied in conjunction with glucose-induced time-dependent potentiation (TDP) to see if the two are related. Islets, isolated from 7-day-old rats, exposed to 16.7 mM glucose for the first time after 30, 75 and 120 minutes of perifusion in Krebs-Ringer bicarbonate buffer (KRB) and 2.8 mM glucose, showed a progressive loss of responsiveness, and less insulin was released at the later times. This run down of the responses was prevented by successive challenges with 16.7 mM glucose and marked TDP was observed. The earlier the islets were exposed to glucose the more effectively was the run down prevented. Also, and perhaps causally related to the prevention of run down, the earlier the exposure to glucose the greater the TDP of a subsequent response. The results could possibly be explained in terms of a shift in metabolism in the isolated 7-day islets, with resultant diminution of the signals for the stimulation of insulin release and TDP. Early, and repeated exposure to high glucose would appear to minimize and delay the metabolic shift.
KeywordsHigh Glucose Insulin Release Closed Circle Stimulate Insulin Secretion Glucose Challenge
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