TIME-COURSE FOR EFFECTS OF HYPOGLYCEMIA ON INSULIN GENE-TRANSCRIPTIONIN-VIVO

The purpose of these studies was to determine the time course for onse t of effects of hypoglycemia on insulin gene transcription in vivo. Us ing insulin infusions, we found that insulin-induced hypoglycemia decr eased levels of precursors for insulin mRNA, reflecting changes in new mRNA synthesis, to new steady-state values within 100 min. These chan ges were followed by declines in processed insulin mRNA. An alternate infusion technique was developed to lower plasma glucose levels from a constant level of 120-130 to 50-60 mg/dl in <10 min without changing insulin levels from those maintained during a preceding 1-h control pe riod. Using this protocol, we found that levels of precursors for insu lin mRNA remained constant for the first 20 min of hypoglycemia, then decreased rapidly at 40 and 60 min. The initial delay followed by rapi d decline suggests that the decrease of insulin gene transcription in response to hypoglycemia is an active process requiring one or more in ductive events before implementation.