INSULIN-LIKE GROWTH-FACTOR I INHIBITS GLUCOSE-STIMULATED INSULIN-SECRETION BUT DOES NOT IMPAIR GLUCOSE-METABOLISM IN NORMAL HUMANS

The effect of human recombinant insulin-like growth factor I (rhIGF-1) on glucose stimulated insulin secretion was studied in 14 healthy human volunteers. Each subject received a primed-continuous infusion of rhIGF-1 (20 mug kg prime, 0.4 mug kg-1 min-1) or saline while plasma glucose was raised + 2.8 mmol/l (+ 50 mg/dl)-(n = 6) or + 7.0 mmol/l (+ 125 mg/dl) (n = 8) above baseline for 2 h using the hyperglycemic clamp technique. Total IGF-1 levels during the IGF-1 studies increased from 196+/-37 to 449+/-71 ng/ml. At the +2.8 mmol/l (+50 mg/dl) stimulus, first and second phase C-peptide levels were suppressed during IGF-I infusion vs control (885+/-157 vs 544+/-99 pmol/l, p<0.05 and 1379+/-246 vs 832+/-130 pmol/l, p<0.05, respectively), whereas insulin levels were suppressed during the second phase only (215+/-43 vs 151+/-28 pmol/l, p<0.05). Despite this, the rate of glucose metabolism was two-fold higher in the IGF-1 infused group (8.0+/-0.5 vs 3.5+/-0.1 mg kg-1 min-1, p<0.01). At the higher glucose stimulus +7.0 mmol/l (+ 125 mg/dl) only second phase C-peptide levels were significantly reduced (1922+/-251 vs 1466+/-74 pmol/l, p<0.05). Again, rates of glucose metabolism were higher during IGF-1 infusion (11.8+/-1.2 vs 8.9+/-0.8 mg kg-1 min-1, p<0.01). These data suggest that rhIGF-1 inhibits glucose-stimulated insulin secretion in humans, but that this inhibitory effect is partially overcome by increasing the hyperglycemic stimulus. Moreover, despite the decrease in insulin secretion, glucose disposal is accelerated by rhIGF-1.