Diabetologia

, Volume 35, Issue 12, pp 1151–1158 | Cite as

Effects of C-peptide on blood flow, capillary diffusion capacity and glucose utilization in the exercising forearm of Type 1 (insulin-dependent) diabetic patients

  • B. -L. Johansson
  • B. Linde
  • J. Wahren
Originals

Summary

Microvascular dysfunction is frequently seen in patients with Type 1 (insulin-dependent) diabetes. The present study was undertaken to examine whether skeletal muscle microcirculation in Type 1 diabetic patients is influenced by C-peptide. Forearm blood flow, capillary diffusion capacity and substrate exchange were studied during strenuous rhythmic forearm exercise on a hand ergometer. Measurements were made before and during i.v. infusion for 60 min of C-peptide or 0.9% NaCl in Type 1 diabetic patients and healthy subjects. During infusion the C-peptide levels in the diabetic patients increased from less than 0.05 nmol/l to 1.32±0.08 nmol/l. Prior to infusion forearm blood flow and capillary diffusion capacity during exercise were lower in the diabetic patients than the control subjects. During C-peptide infusion both variables increased in the diabetic patients (blood flow +27±4%, capillary diffusion capacity +52±9%) to levels similar to those in the healthy subjects, while no significant change was seen in the healthy control subjects or the diabetic patients given NaCl. Forearm uptake of oxygen and glucose in the diabetic patients increased markedly after C-peptide administration but were unchanged after NaCl infusion. Significant uptake of C-peptide to the deep forearm tissues was observed in the resting state; approximately 7±2% of the arterial C-peptide concentration was extracted by forearm tissues in diabetic patients as well as in healthy control subjects. It is concluded that replacement of C-peptide to physiological levels in young Type 1 diabetic patients results in a normalization of both blood flow and capillary diffusion capacity during exercise, as well as augmented uptake of oxygen and glucose by exercising muscle. The findings suggest that C-peptide may be of importance for microvascular function in exercising muscle in Type 1 diabetes. Finally, skeletal muscle is a major site of C-peptide disposal.

Key words

Hand ergometer indicator-diffusion technique lactate exchange oxygen uptake skeletal muscle substrate exchange vascular resistance 

References

  1. 1.
    Steiner DF, Kemmler W, Howard S, Peterson J (1974) Proteolytic processing in the biosynthesis of insulin and other proteins. Fed Proc 33: 2105–2115PubMedGoogle Scholar
  2. 2.
    Steiner D (1978) On the role of the proinsulin C-peptide. Diabetes 27 [Suppl 1]: 145–148PubMedGoogle Scholar
  3. 3.
    Kitabchi AE (1970) The biological and immological properties of pork and beef insulin, proinsulin, and connecting peptides. J Clin Invest 49: 979–987PubMedGoogle Scholar
  4. 4.
    Solomon SS, Brush JS, Kitabchi AE (1970) Antilipolytic activity on ACTH and cyclic nucleotide-induced lipolysis in the isolated adipose cell of rat. Biochem Biophys Acta 218: 167–169PubMedGoogle Scholar
  5. 5.
    Yu SS, Kitabchi AE (1973) Biological activity of insulin and proinsulin and related polypeptides in the fat tissue. J Biol Chem 248: 3753–3761PubMedGoogle Scholar
  6. 6.
    Kitabchi AE (1977) Proinsulin and C-peptide: a review. Metabolism 26: 547–587CrossRefPubMedGoogle Scholar
  7. 7.
    Johansson B-L, Sjöberg S, Wahren J (1992) The influence of human C-peptide on renal function and glucose utilization in type 1 (insulin-dependent) diabetic patients. Diabetologia 35: 121–128PubMedGoogle Scholar
  8. 8.
    Johansson B-L, Kernell A, Sjöberg S, Wahren J (1991) Effects of C-peptide on renal function, blood-retinal barrier leakage and metabolic control in type 1 diabetes. Diabetologia 34 [Suppl 2]: A 184 (Abstract)Google Scholar
  9. 9.
    Sjöberg S, Johansson B-L, Östman J, Wahren J (1991) Renal and splanchnic exchange of human biosynthetic C-peptide in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 34: 423–428PubMedGoogle Scholar
  10. 10.
    Zierath JR, Galuska D, Johansson B-L, Wallberg-Henriksson H (1991) Effect of human C-peptide on glucose transport in in vitro incubated human skeletal muscle. Diabetologia 34: 899–901PubMedGoogle Scholar
  11. 11.
    Trap-Jensen J, Lassen NA (1970) Capillary permeability for smaller hydrophilic tracers in exercising muscle in normal man and in patients with long term diabetes. In: Crone C, Lassen NA (eds) Alfred Benzon Symp II. Capillary permeability. Munksgaard, Copenhagen, pp 135–152Google Scholar
  12. 12.
    Trap-Jensen J (1970) Increased capillary permeability to 131Iodide and [51Cr] EDTA in the exercising forearm of longterm diabetics. Clin Sci 39: 39–49PubMedGoogle Scholar
  13. 13.
    Garby L, Vuille JC (1961) The amount of trapped plasma in high speed micro-capillary hematocrit centrifuge. Scand J Clin Lab Invest 13: 642–645PubMedGoogle Scholar
  14. 14.
    Heding LG (1975) Radioimmunological determination of human C-peptide in serum. Diabetologia 11: 541–548PubMedGoogle Scholar
  15. 15.
    Arnqvist H, Olsson P-O, von Shenk H (1987) Free and total insulin determined after precipitation with polyethylene glycol: analythic characteristics and effects of sample handlings and storage. Clin Chem 33: 93–96PubMedGoogle Scholar
  16. 16.
    Persson MG (1991) Studies on metabolic, myogenic, and neurogenic control of skeletal muscle microcirculation. Thesis, Karolinska Institute ISBN 91-628-0418-9Google Scholar
  17. 17.
    Dieterle P, Birkner B, Gmeiner K-H et al. (1973) Release of peripherally stored insulin during acute muscular work in man. Horm Metab Res 5: 316–322PubMedGoogle Scholar
  18. 18.
    Flatt PR, Swanston-Flatt SK, Hampton SM, Bailey CJ, Marks V (1986) Specific binding of the C-peptide of proinsulin to cultured B-cells from a transplantable rat islet cell tumor. Biosci Rep 6: 196–199Google Scholar
  19. 19.
    Trap-Jensen J (1971) Permeability of small vessels in diabetes. Acta Diabet Lat 8 [Suppl 1]: 192–202Google Scholar
  20. 20.
    Sjöberg S, Gjötterberg M, Berglund L, Möller E, Östman J (1991) Residual C-peptide excretion is associated with better longterm glycemic control and slower progress of retinopathy in type 1 (insulin-dependent) diabetes mellitus. J Diab Compl 5: 18–22Google Scholar
  21. 21.
    Kernell A, Ludvigsson J, Finnström K (1990) Vitreous fluorophotometry in juvenile diabetics with and without retinopathy in relation to metabolic control; Insulin antibodies and C-peptide levels. Acta Opthalmologica 68: 415–420Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • B. -L. Johansson
    • 1
  • B. Linde
    • 1
  • J. Wahren
    • 1
  1. 1.Department of Clinical Physiology, Karolinska HospitalKarolinska InstituteStockholmSweden

Personalised recommendations