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Insulin and C-peptide plasma levels in patients with severe chronic pancreatitis and fasting normoglycemia

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Abstract

The aim of the present study was to evaluate insulin secretion by the pancreatic B cell in a group of patients with severe chronic pancreatitis and without overt diabetes. For this purpose we have measured plasma insulin and C-peptide peripheral levels in the fasting state and after a 100-g oral glucose load in 10 patients with severe chronic pancreatitis and fasting normoglycemia, and in 10 sex-, age-, and weight-matched healthy controls. As compared to normal subjects, patients with chronic pancreatitis showed: (1) significantly higher plasma glucose levels after oral glucose load (area under the plasma glucose curve 1708±142 vs 1208±47 mmol/liter × 240 min, P < 0.005); (2) plasma insulin levels significantly higher at fasting (0.11±0.008 vs 0.08±0.005 nmol/liter, P < 0.01) but not after oral glucose administration (area under the plasma insulin curve 79±12 vs 88 ±16 nmol/liter × 240 min); (3) significantly lower plasma C-peptide concentrations both in the fasting state (0.15±0.01 vs 0.54±0.05 nmol/liter, P<0.001) and after oral glucose load (area under the plasma C-peptide curve 211±30 vs 325±37 nmol/liter × 240 min, P<0.05). The finding of diminished plasma C-peptide levels suggests that chronic pancreatitis is associated with an impaired B-cell function even in the absence of overt diabetes. The increased or unchanged plasma insulin levels in spite of decreased plasma C-peptide concentrations indicate that in chronic pancreatitis insulin metabolism is reduced, most likely within the liver.

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References

  1. Anderson MF, Davison, SHH, Dick AP, Hales CN, Owens J: Plasma insulin in pancreatic disease. Gut 11:524–531, 1970

    PubMed  Google Scholar 

  2. Grabner W, Phillip J, Strigl P: The diagnostic value of oral glucose tolerance test and combined B-cell stimulation in chronic pancreatitis. Am J Dig Dis 18:1055–1060, 1973

    PubMed  Google Scholar 

  3. Seligson U, Cho JW, Nygren A, Reichard P: Is glucose intolerance after pancreatitis related to pancreatic tissue damage? Acta Med Scand 213:119–122, 1983

    PubMed  Google Scholar 

  4. Field JB: Extraction of insulin by liver. Annu Rev Med 24:309–314, 1973

    PubMed  Google Scholar 

  5. Johnston DG, Alberti KGMM, Faber OK, Binder C, Wright R: Hyperinsulinism of hepatic cirrhosis: diminished degradation or hypersecretion? Lancet 1:10–12, 1977

    PubMed  Google Scholar 

  6. Iwasaki Y, Ohkubo A, Kajinuma H, Akanuma Y, Kosaka K: Degradation and secretion of insulin in hepatic cirrhosis. J Clin Endocrinol Metab 47:774–779, 1978

    PubMed  Google Scholar 

  7. Bonora E, Coscelli C, Orioli S, Cambi R, Buzzelli G, Gentilini P, Butturini U: Hyperinsulinemia of chronic active hepatitis: Impaired insulin removal rather than pancreatic hypersecretion. Horm Metab Res 16:111–114, 1984

    PubMed  Google Scholar 

  8. Horwitz DL, Starr JI, Mako ME, Blackard WG, Rubenstein AH: Proinsulin, insulin, and C-peptide concentration in human portal and peripheral blood. J Clin Invest 55:1278–1283, 1975

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  10. Bratusch-Marrain P, Waldhausl W, Gasic S, Hofer A: Hepatic disposal of biosynthetic human insulin and porcine C-peptide in humans. Metabolism 33:151–157, 1984

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  12. Polonsky KS, Pugh W, Jaspan JB, Cohen DM, Karrison T, Tager HS, Rubenstein AH: C-peptide and insulin secretion. Relationship between peripheral concentrations of C-peptide and insulin and their secretion rates in the dog. J Clin Invest 74:1821–1829, 1984

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  15. Licinio-Paixao J, Polonsky KS, Given BD, Pugh W, Ostrega D, Frank BF, Rubenstein AH: Ingestion of a mixed meal does not affect the metabolic clearance rate of biosynthetic human C-peptide. J Clin Endocrinol Metab 63:401–403, 1986

    PubMed  Google Scholar 

  16. Sando H, Lee YS, Iwamoto Y, Ikeuchi M, Kosaka K: Isoproterenol-stimulated C-peptide and insulin secretion in diabetic and nonobese normal subjects: Decreased hepatic extraction of endogenous insulin in diabetes. J Clin Endocrinol Metab 51:1143–1149, 1980

    PubMed  Google Scholar 

  17. Faber OK, Christensen K, Kehlet H, Madsbad S, Binder C: Decreased insulin removal contributes to hyperinsulinemia in obesity. J Clin Endocrinol Metab 53:618–621, 1981

    PubMed  Google Scholar 

  18. Madsbad S, Kehlet H, Hilsted J, Tronier B: Discrepancy between plasma C-peptide and insulin response to oral and intravenous glucose. Diabetes 32:436–438, 1983

    PubMed  Google Scholar 

  19. Bonora E, Zavaroni I, Coscelli C, Butturini U: Decreased hepatic insulin extraction in subjects with mild glucose intolerance. Metabolism 32:438–446, 1983

    PubMed  Google Scholar 

  20. Bonora E, Zavaroni I, Bruschi F, Alpi O, Pezzarossa A, Guerra L, Dall'Aglio E, Coscelli C, Butturini U: Peripheral hyperinsulinemia of simple obesity: pancreatic hypersecretion or impaired insulin metabolism? J Clin Endocrinol Metab 59:1121–1127, 1984

    PubMed  Google Scholar 

  21. Lesi C, Scandellari A, Cucci AM, Franceschi F, Matacena C, Malaguti P: Changes in serum pancreatic enzymes after hormonal stimulation in chronic pancreatitis. Dig Dis Sci 30:552–556, 1985

    PubMed  Google Scholar 

  22. Hales CN, Randle PJ: Immunoassay of insulin with insulin-antibody precipitate. Biochem J 88:137–146, 1963

    PubMed  Google Scholar 

  23. Kaneko T, Oka H, Munemura M, Oda T, Yamashita K, Suzuki S, Yanaihara N, Hashimoto T, Yanaihara C: Radioimmunoassay of human proinsulin C-peptide using synthetic human connecting peptide. Endocrinol Jpn 21:141–145, 1974

    PubMed  Google Scholar 

  24. Tallaride RJ, Murray RB: Manual of Pharmacologic Calculations. Berlin, Springer-Verlag, 1981, pp 47–49

    Google Scholar 

  25. Joffe BI, Bank S, Jackson WPU, Keller P, O'Reilly TG, Vinik AI: Insulin reserve in patients with chronic pancreatitis. Lancet 2:121–124, 1968

    Google Scholar 

  26. Ohlsen P: Endocrine and exocrine pancreatic function in pancreatitis. Acta Med Scand Suppl 484:7–99, 1968

    Google Scholar 

  27. Kalk WJ, Vinik AI, Bank S, Keller P, Jackson WPU: Selective loss of beta cell response to glucose in chronic pancreatitis. Horm Metab Res 6:95–98, 1974

    PubMed  Google Scholar 

  28. Peters N, Dick AP, Hales CN, Orrell DH, Sarner M: Exocrine and endocrine pancreatic function in diabetes mellitus and chronic pancreatitis. Gut 7:277–281, 1966

    Google Scholar 

  29. Duckworth WC, Solomon SS, Jallepalli P, Iyer R, Bobal MA: Hormonal response to intravenous glucose and arginine in patients with pancreatitis. Horm Res 17:65–73, 1983

    PubMed  Google Scholar 

  30. Bank S, Marks IN, Vinik AI: Clinical and hormonal aspects of pancreatic diabetes. Am J Gastroenterol 64:13–22, 1975

    PubMed  Google Scholar 

  31. Keller P, Bank S, Jackson WPU, Marks IN, O'Reilly IG: Plasma insulin levels in “pancreatic diabetes”. Lancet 2:1211–1213, 1965

    PubMed  Google Scholar 

  32. McKiddie MT, Buchanan KD, McBain GC, Bell G: The insulin response to glucose in patients with pancreatic disease. Postgrad Med J 45:726–730, 1969

    PubMed  Google Scholar 

  33. Goldstein BJ, Livingston JN: Insulin degradation by insulin target cells. Metabolism 30:825–835, 1981

    Google Scholar 

  34. Bonora E, Orioli S, Coscelli C, Buzzelli G, Butturini U, Gentilini P: Glucose tolerance, insulin secretion and insulin removal in chronic persistant hepatitis. Horm Metab Res 16:449–450, 1984

    PubMed  Google Scholar 

  35. Bank S.: Chronic pancreatitis: Clinical features and medical management. Am J Gastroenterol 81:153–167, 1987

    Google Scholar 

  36. Polonsky KS, Rubenstein AH: C-peptide as a measure of the secretion and hepatic extraction of insulin. Pitfalls and limitations. Diabetes 33:486–494, 1984

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Clinica Medica Generale, Parma University Medical School, Parma

    E. Bonora MD, C. Rizzi MD, C. Lesi MD, P. Berra MD, C. Coscelli MD & U. Butturini MD

  2. Department of Medicine and Gastroenterology, Bologna Hospital, Bologna, Italy

    E. Bonora MD, C. Rizzi MD, C. Lesi MD, P. Berra MD, C. Coscelli MD & U. Butturini MD

Authors
  1. E. Bonora MD
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  2. C. Rizzi MD
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  3. C. Lesi MD
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  4. P. Berra MD
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  5. C. Coscelli MD
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  6. U. Butturini MD
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Supported by grant 85.00775.04 from C.N.R., Rome, Italy.

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Bonora, E., Rizzi, C., Lesi, C. et al. Insulin and C-peptide plasma levels in patients with severe chronic pancreatitis and fasting normoglycemia. Digest Dis Sci 33, 732–736 (1988). https://doi.org/10.1007/BF01540438

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  • DOI: https://doi.org/10.1007/BF01540438

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