Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Basal and 24-h C-peptide and insulin secretion rate in normal man


An understanding of the metabolic abnormalities rising from inappropriate insulin delivery in diabetic patients demands a knowledge of 24-h and basal insulin secretion rates in normal man. We have used biosynthetic human C-peptide to determine its kinetic parameters in 10 normal subjects and applied these to measurements of plasma concentrations in the same subjects to determine pancreatic secretion rate. Metabolic clearance rate measured by stepped primed infusion of biosynthetic human C-peptide at rates of 10, 19 and 26nmol/h was 4.7±0.7 (±SD) ml·kg−1·min−1, and was independent of infusion rate. Fractional clearance (T1/2, 26±3 min) and distribution volume (0.178±0.039 l/kg) were calculated from the decline in concentration after cessation of the highest rate infusion. Basal insulin secretion calculated from the C-peptide metabolic clearance rate and plasma concentrations for the period 02.00 to 07.00 hours was 1.3±0.4U/h. Over 24h total insulin secretion on a standard high carbohydrate diet was 63±15 U, calculated from the area under the C-peptide concentration curve. Basal insulin secretion, therefore, accounted for 50±8% of total insulin secretion. Although only 5.6±1.1% of C-peptide was detected in 24-h urine collections, urinary C-peptide excretion was significantly related to 24-h C-peptide secretion (r=0.74,p<0.02).


  1. 1.

    Blackard WG, Nelson NC (1970) Portal and peripheral vein immunoreactive insulin concentrations before and after glucose infusion. Diabetes 19: 302–306

  2. 2.

    Jaspan JB, Polonsky K (1982) Glucose ingestion in dogs alters the hepatic extraction of insulin: in vivo evidence for a relationship between biologic action and extraction of insulin. J Clin Invest 69: 516–525

  3. 3.

    Rubenstein AH, Clark JL, Melani F, Steiner DF (1969) Secretion of proinsulin C-peptide by pancreatic beta cells and its circulation in blood. Nature (Lond) 224: 697–699

  4. 4.

    Polonsky K, Jaspan JB, Pugh W, Cohen D, Schneider M, Schwartz T, Moossa AR, Tager H, Rubenstein AH (1983) Metabolism of C-peptide in the dog. In vivo demonstration of the absence of hepatic extraction. J Clin Invest 72: 1114–1123

  5. 5.

    Waldhausl W, Bratusch-Marrain P, Gasic S, Korn A, Nowotny P (1979) Insulin production rate following glucose ingestion estimated by splanchnic C-peptide output in normal man. Diabetologia 17: 221–227

  6. 6.

    Eaton RP, Allen RC, Schade DS, Erickson KM, Standefer J (1980) Prehepatic insulin production in man: kinetic analysis using peripheral connecting peptide behaviour. J Clin Endocrinol Metab 51: 520–528

  7. 7.

    Meistas MT, Zadik Z, Margolis S, Kowarski AA (1981) Correlations of urinary excretion of C-peptide with the integrated concentration and secretion rate of insulin. Diabetes 30: 639–643

  8. 8.

    Faber OK, Hagen C, Binder C, Markussen J, Naithani VK, Blix PM, Kuzuya H, Horwitz DL, Rubenstein AH, Rossing N (1978) Kinetics of human connecting peptide in normal and diabetic subjects. J Clin Invest 62: 197–203

  9. 9.

    Caygill CPJ, Gaines Das RE, Bomgham DR (1980) Use of a common standard for comparison of insulin C-peptide measurements by different laboratories. Diabetologia 18: 197–204

  10. 10.

    Polonsky KS, Licinio-Paixao J, Given BD, Pugh W, Rue P, Galloway J, Karrison T, Frank B (1986) Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type 1 diabetic patients. J Clin Invest 77: 98–105

  11. 11.

    Bonser AM, Garcia-Webb P (1984) C-peptide measurement: methods and clinical utility. CRC Crit Rev Clin Lab Sci 19: 297–352

  12. 12.

    Soeldner JS, Sloane D (1965) Critical variables in the radioimmunoassay of serum insulin using the double-antibody technique. Diabetes 14: 771–779

  13. 13.

    Heding LG (1975) Radioimmunological determination of human C-peptide in serum. Diabetologia 11: 541–548

  14. 14.

    Pingel M, Vølund A, Sørensen E, Sørensen AR (1982) Assessment of insulin potency by chemical and biological methods. In: Gueriguian JL, Bransome ED, Outschoorn AS (eds) Hormone drugs. United States Pharmacopeial Convention, Inc, Rockville, pp 200–207

  15. 15.

    Royal College of Physicians of London (1983) Obesity. A report of the Royal College of Physicians. J R Coll Physicians Lond 17: 5–65

  16. 16.

    Polonsky K, Rubenstein AH (1984) C-peptide as a measure of the secretion and hepatic extraction of insulin: pitfalls and limitations. Diabetes 33: 486–494

  17. 17.

    Polonsky K, Frank B, Pugh W, Addis A, Karrison T, Meier P, Tager H, Rubenstein A (1986) The limitations to and valid use of C-peptide as a marker of the secretion of insulin. Diabetes 35: 379–386

  18. 18.

    Faber OK, Binder C, Markussen J, Heding LG, Naithani VK, Kuzuya H, Blix PM, Horwitz DL, Rubenstein AH (1978) Characterisation of seven C-peptide antisera. Diabetes 27 [Suppl 1]: 70–77

  19. 19.

    Katz AI, Rubenstein AH (1973) Metabolism of proinsulin, insulin and C-peptide in the rat. J Clin Invest 52: 1113–1121

  20. 20.

    Kenny AJ, Maroux S (1982) Topology of microvillar membrane hydrolases of kidney and intestine. Physiol Rev 62: 91–128

  21. 21.

    Home PD, Capaldo B, Burrin JM, Worth R, Alberti KGMM (1982) A crossover comparison of continuous subcutaneous insulin infusion (CSII) against multiple insulin injections in insulin-dependent diabetic subjects: improved control with CSII. Diabetes Care 5: 466–471

  22. 22.

    Home PD, Massi-Benedetti M, Shepherd GAA, Hanning I, Alberti KGMM, Owens DR (1982) A comparison of the activity and disposal of semi-synthetic human insulin and porcine insulin in normal man by the glucose clamp technique. Diabetologia 22: 41–45

  23. 23.

    Waldhausl W, Bratusch-Marrain P, Gastic S, Korn A, Nowotny P (1982) Insulin production rate, hepatic insulin retention and splanchnic carbohydrate metabolism after oral glucose ingestion in hyperinsulinaemic type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 23: 6–15

  24. 24.

    Home PD, Mann NP, Hutchison AS, Park R, Walford S, Murphy M, Reeves WG (1984) A fifteen-month double-blind cross-over study of the efficacy and antigenicity of human and pork insulins. Diabetic Med 1: 93–98

  25. 25.

    Yki Jarvinen H, Koivisto V (1984) Continuous subcutaneous insulin infusion therapy decreases insulin resistance in type 1 diabetes. J Clin Endocrinol Metab 58: 659–666

  26. 26.

    Kruszynska YT, Home PD, Alberti KGMM (1985) Comparison of portal and peripheral insulin delivery on carbohydrate metabolism in streptozotocin diabetic rats. Diabetologia 28: 167–171

  27. 27.

    Kruszynska YT, Home PD, Agius L, Alberti KGMM (1986) Hepatic glycogen metabolism and insulin receptor status after long term peripheral insulin delivery in the islet transplanted diabetic rat. Diabetes 35: 306–310

  28. 28.

    Harding PE, Bloom G, Field JB (1975) Effect of infusion of insulin into portal vein on hepatic extraction of insulin in anaesthetised dogs. Am J Physiol 228: 1580–1588

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kruszynska, Y.T., Home, P.D., Hanning, I. et al. Basal and 24-h C-peptide and insulin secretion rate in normal man. Diabetologia 30, 16–21 (1987).

Download citation

Key words

  • C-peptide
  • insulin secretion
  • C-peptide pharmacokinetics
  • insulin dose