Effects of short-term hyperglycemia on insulin secretion in normal humans.
Stepwise glucose clamps were used to study beta-cell insulin response to glucose in normal and noninsulin-dependent diabetic subjects and to study changes in response after hyperglycemia. In normal subjects, insulin increment, delta I, correlated with glucose increment above basal, delta G, during the first 6 min of hyperglycemia, r = 0.748, P less than 0.0001. After 1 h of hyperglycemia, mean delta I/ delta G was reduced from 50 to 23 (mean difference 23 +/- 5) pmol/mmol, P = 0.0002; but delta I/% change in glucose (delta G') was unaltered (2.3 vs. 1.7, mean difference 0.4 +/- 0.3 pmol/%). Second-phase response correlated with mean glucose elevation (r = 0.835, P less than 0.0001), and no plateau was reached after 3 h at 3 mmol/l above basal glucose (rate of change of insulin concentration = 0.5; range, 0.3-0.8 pmol . l-1 . min-1). In diabetic subjects, delta I/ delta G was 20% of normal, while delta I/ delta G' was 63% of normal and second-phase response 30% of normal. We conclude that hyperglycemia per se reduces delta I/ delta G and must be considered when assessing insulin responses. Noninsulin-dependent diabetic subjects have defective first- and second-phase responses.
D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005260:Female; D005947:Glucose; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D011384:Proinsulin / Q000378:metabolism
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D011384:Proinsulin; D005947:Glucose