Peripheral insulin parallels changes in insulin secretion more closely than C-peptide after bolus intravenous glucose administration.

The changes in peripheral serum insulin and plasma C-peptide levels and in the insulin secretory rate in response to iv glucose (0.5 g/kg BW) administration were studied in seven normal subjects. Insulin secretory rates were calculated according to a two-compartment model of distribution for C-peptide, using individual C-peptide kinetics calculated from iv bolus injections of biosynthetic human C-peptide. The mean plasma glucose level increased from a fasting level of 5.1 +/- 0.1 (+/- SE) to a peak of 24.0 +/- 1.0 mmol/L at 3 min and reached basal levels 101 +/- 6 min after glucose administration. The mean serum insulin value increased from 50 +/- 12 to a peak of 405 +/- 58 pmol/L at 3 min and then declined to fasting levels 139 +/- 14 min after the stimulus. In contrast, the mean plasma C-peptide level increased from 390 +/- 50 to a peak of 1460 +/- 210 pmol/L at 3 min and only began declining 45 min after glucose administration, reaching fasting levels 191 +/- 15 min after the stimulus. The mean insulin secretory rate increased from 69.8 +/- 19.9 to a peak of 1412.7 +/- 159.1 pmol/min at 3 min (15.3 +/- 2.5-fold elevation over baseline) and reached basal levels 135 +/- 12 min after the stimulus. The clearance of endogenous insulin during the basal period (2.505 +/- 0.365 L/min) and that during the 4 h after the stimulus (2.319 +/- 0.230 L/min) were similar. In conclusion, after bolus iv glucose administration: 1) the insulin secretory rate is more closely represented by changes in peripheral serum insulin than in plasma C-peptide levels; and 2) no change in endogenous insulin clearance occurs.

[1]  J. Tait,et al.  REVIEW: THE USE OF ISOTOPIC STEROIDS FOR THE MEASUREMENT OF PRODUCTION RATES IN VIVO. , 1963, The Journal of clinical endocrinology and metabolism.

[2]  D. Steiner,et al.  The metabolism of proinsulin and insulin by the liver. , 1972, The Journal of clinical investigation.

[3]  K. M. Erickson,et al.  Prehepatic insulin production in man: kinetic analysis using peripheral connecting peptide behavior. , 1980, The Journal of clinical endocrinology and metabolism.

[4]  W. Cleveland Robust Locally Weighted Regression and Smoothing Scatterplots , 1979 .

[5]  B H Frank,et al.  Quantitative study of insulin secretion and clearance in normal and obese subjects. , 1988, The Journal of clinical investigation.

[6]  D. Porte,et al.  Abnormalities of islet B-cell function, insulin action, and fat distribution in women with histories of gestational diabetes: relationship to obesity. , 1985, The Journal of clinical endocrinology and metabolism.

[7]  K. Polonsky,et al.  Ingestion of a mixed meal does not affect the metabolic clearance rate of biosynthetic human C-peptide. , 1986, The Journal of clinical endocrinology and metabolism.

[8]  G. Eisenbarth,et al.  First-degree relatives of patients with type I diabetes mellitus. Islet-cell antibodies and abnormal insulin secretion. , 1985, The New England journal of medicine.

[9]  A. Lazarow,et al.  Immunoassay of Insulin: Two Antibody System: Plasma Insulin Levels of Normal, Subdiabetic and Diabetic Rats , 1963, Diabetes.

[10]  Bruce H. Frank,et al.  Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. , 1986, The Journal of clinical investigation.

[11]  G. Eisenbarth,et al.  Autoimmunity to Insulin, Beta Cell Dysfunction, and Development of Insulin-dependent Diabetes Mellitus , 1986, Diabetes.

[12]  K. Polonsky,et al.  The Limitations to and Valid Use of C-Peptide as a Marker of the Secretion of Insulin , 1986, Diabetes.

[13]  C. Metzler Usefulness of the Two-Compartment Open Model in Pharmacokinetics , 1971 .

[14]  K. Polonsky,et al.  Insulin Secretion and Clearance: Comparison After Oral and Intravenous Glucose , 1987, Diabetes.

[15]  H. Kuzuya,et al.  Characterization of Seven C-peptide Antisera , 1978, Diabetes.

[16]  D L Horwitz,et al.  Kinetics of human connecting peptide in normal and diabetic subjects. , 1978, The Journal of clinical investigation.

[17]  K. Polonsky,et al.  C-Peptide as a Measure of the Secretion and Hepatic Extraction of Insulin: Pitfalls and Limitations , 1984, Diabetes.