Glucose stimulated proinsulin biosynthesis rates of turn off after cessation of the stimulus.

Proinsulin biosynthesis was stimulated progressively to a plateau level at 45 min by 5.5 mmol/1 glucose. The rate of biosynthesis promptly decreased following cessation of either 15 or 60 min exposure to this concentration of glucose. Actinomycin D had no effect on the rate of decline. In contrast, exposure to 20 mmol/1 glucose caused a prolonged increase in proinsulin biosynthesis which was still apparent at 75 min. After removal of the stimulus there was an initial decrease in the rate of proinsulin biosynthesis followed by persistently elevated rates. When proinsulin biosynthesis was stimulated by 20 mmol/1 glucose in the presence of actinomycin D, there was a rapid switch off of biosynthesis and no persistent effect. Thus, two controls for regulation of proinsulin biosynthesis can be characterised: a prompt, rapidly reversible stimulation in response to low or high glucose concentrations and a persistent stimulation in response to high glucose concentrations. These two effects may represent the translational and transcriptional effects of glucose respectively.