Reduction of insulin clearance during hyperglycemic clamp. Dose-response study in normal humans.
Insulin secretion and clearance were studied in eight normal subjects who underwent hyperglycemic clamp studies at plasma glucose levels of 120, 225, and 300 mg/dl on three occasions. Insulin secretion rates were calculated during a 1-h baseline period and during 3 h of glucose clamping from a two-compartmental analysis of peripheral C-peptide concentrations with individual kinetic parameters derived after intravenous bolus injections of biosynthetic human C-peptide. At the 300-mg/dl clamp level, the insulin secretion rate increased to a value 9.9 +/- 0.7 times that of basal at the end of the clamp (mean +/- SE), whereas over the same period, the peripheral insulin concentrations increased to a greater extent, reaching a value 15.4 +/- 1.2 times that of basal (P = .002). This greater relative increase in the insulin concentration in comparison with the corresponding insulin secretion rate suggests a reduction in the clearance of endogenous insulin. A similar trend was seen at the 225-mg/dl clamp level, but the relative increase in the insulin concentration (9.9 +/- 1.5 times that of basal) was not significantly higher than the relative increase in the insulin secretion rate (8.1 +/- 0.5 times that of basal, P = .17). At the 120-mg/dl clamp level, the relative increases in the insulin secretion rate (2.7 +/- 0.2 times that of basal) and the insulin concentration (2.4 +/- 0.2 times that of basal) were similar (P = .26), indicating no reduction in endogenous insulin clearance during moderate stimulation of insulin secretion. In conclusion, a reduction in endogenous insulin clearance occurs during greater stimulation of insulin secretion at higher glucose-clamp levels.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D001481:Basal Metabolism; D001786:Blood Glucose / Q000032:analysis*; D002096:C-Peptide / Q000008:administration & dosage* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000008:administration & dosage*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005947:Glucose