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Basal and nutrient-stimulated pancreatic and gastrointestinal hormone concentrations in type-l-diabetic patients after successful combined pancreas and kidney transplantation

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Summary

The secretion of pancreatic and gastrointestinal hormones in the basal state and after nutrient stimuli (50 g glucose, 50 g protein, or 30 g triglyceride administered on separate occasions) was assessed in ten previously type-1-diabetic patients after successful combined kidney and pancreas transplantation (systemic venous drainage). Fasting values were compared to matched non-diabetic kidney-transplanted patients and related to kidney function (endogenous creatinine clearance) and to the type and dosage of immunosuppressive medication. In the fasting state, only IR insulin concentrations were higher in pancreas-kidney-transplanted patients (by 88%; P=0.001) than in the kidney graft recipients. There were significant inverse correlations of plasma C-peptide, GIP, and gastrin immunoreactivity to endogenous creatinine clearance (kidney function). In response to nutrients, insulin secretion (IR insulin, C-peptide) was significantly stimulated by glucose, and — to a lesser degree — also by protein. Pancreatic glucagon was suppressed by glucose and stimulated by protein ingestion. GIP was raised after glucose and triglyceride more than after protein (P=0.0003). GLP-1 immunoreactivity was stimulated by all nutrients, with a tendency towards higher responses to protein and fat (P=0.06). Gastrin was mainly raised by protein. In conclusion, the overall pattern of pancreatic and gastrointestinal hormone release is normal in patients after combined pancreas-kidney-transplantation, but there are some peculiarities due to (a) systemic venous drainage of the pancreas graft (elevated fasting IR insulin) and (b) impaired kidney function (negative correlation of fasting plasma values to endogenous creatinine clearance for C-peptide, GIP, and gastrin). The plasma levels of these important regulatory peptides and their responses to nutrient stimulation are compatible with and may contribute to the well-preserved endocrine function of the pancreatic grafts (normal or slightly impaired glucose tolerance, preserved incretin effect).

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Abbreviations

GIP:

Gastric inhibitory polypeptide (glucosedependent insulinotropic polypeptide)

GLP-1:

Glucagon-like peptide 1 [7–36 amide] (proglucagon sequence 78–108 amide)

IR:

immunoreactive

WHO:

World Health Organization

References

  1. Beard JC, Halter JB, Best JD, Pfeiffer MA, Porte D Jr (1984) Dexamethasone-induced insulin resistance enhances B cell responsiveness to glucose level in normal men. Am J Physiol 247:E592–596

    Google Scholar 

  2. Bilbrey GL, Faloona GR, White MG, Knochel JP (1974) Hyperglucagonemia of renal failure. J Clin Invest 53:841–847

    Google Scholar 

  3. Both GB, Dimitriadis GD, Pehling GB, et al (1984) Abnormal glucose counterregulation after subcutaneous insulin in insulin-dependent diabetes mellitus. N Engl J Med 310:1706–1711

    Google Scholar 

  4. Busing M, Nauck M, Hölzer H, et al (1990) Stimulation des transplantierten (denervierten) exokrinen Pankreas beim Menschen. Z Gastroenterol 25:468 (abstract)

    Google Scholar 

  5. Clark JDA, Wheatley T, Brons IGM, Bloom SR, Calne RY (1989) Studies of the entero-insular axis following pancreas transplantation in man: neural or hormonal control? Diabetic Med 6:813–817

    Google Scholar 

  6. Cleator IGM, Gourlay RH (1975) Release of immunoreactive gastric inhibitory polypeptide (IR-GIP) by oral ingestion of food substances. Am J Surg 130:128–135

    Google Scholar 

  7. Creutzfeldt W (1979) The incretin concept today. Diabetologia 16:75–85

    Google Scholar 

  8. Creutzfeldt W, Ebert R (1985) New developments in the incretin concept. Diabetologia 28:565–573

    Google Scholar 

  9. D'Allessandro AM, Stratta RJ, Sollinger HW, Kalayoglu M, Frisch JD, Belzer FO (1989) Use of UW solution in pancreas transplantation. Diabetes 38 [Suppl 1]:7–9

    Google Scholar 

  10. DeFronzo RA, Tobin JD, Rowe JW, Andres R. Glucose intolerance in uremia (1978) Quantification of pancreatic beta cell sensitivity to glucose and tissue sensitivity to insulin. J Clin Invest 62:425–435

    Google Scholar 

  11. Diem P, Abid M, Sutherland DER, Robertson RP (1989) Hyperglucagonemia and improved glucagon response to hypoglycemia in type I diabetic recipients of pancreas allografts. Diabetes 3 [Suppl]:48 A (abstract)

  12. Diem P, Abid M, Redmon JB, Sutherland DER, Robertson RP (1990) Systemic venous drainage of pancreas allografts as independent cause of hyperinsulinemia in type 1 diabetic recipients. Diabetes 39:534–540

    Google Scholar 

  13. Ferrannini E, Cobelli C (1987) The kinetics of insulin in man. 11. The role of the liver. Diabetes Metab Rev 3:365–397

    Google Scholar 

  14. Fritsch W-P, Hausamen T-U, Rick W (1976) Gastric and extragastric gastrin in normal subjects and duodenal ulcer patients, and in patients with partial gastrectomy (Billroth I). Gastroenterology 71:552–557

    Google Scholar 

  15. Haffner J, Linnestad P, Schrumpf E, Hanssen LE, Flaten O, Oyasaeter S (1987) The immediate effect of human renal transplantation on basal and meal-stimulated levels of gastrointestinal hormones. Scand J Gastroenterol 22:42–46

    Google Scholar 

  16. Henriksen JH, Tronier B, Bülow JB (1987) Kinetics of circulating endogenous insulin, C-peptide, and proinsulin in fasting nondiabetic man. Metabolism 36:463–468

    Google Scholar 

  17. Ito C, Mito K, Hara H (1979) Review of the criteria for diagnosis of diabetes mellitus based on results of a followup-study. Diabetes 28:1039–1057

    Google Scholar 

  18. Kanatsuka A, Osegawa M, An T, Suzuki T, Hashimoto N, Makino H (1984) Augmented gastrin responses in diabetic patients with vagal neuropathy. Diabetologia 26:449–452

    Google Scholar 

  19. Kennedy FP, Bolli GB, Go VLW, Cryer PE, Gerich JE (1987) The significance of impaired pancreatic polypeptide and epinephrine responses to hypoglycemia in patients with insulin-dependent diabetes mellitus. J Clin Endokrinol Metab 64:602–608

    Google Scholar 

  20. Korman MG, Laver MC, Hansky J (1972) Hypergastrinaemia in chronic renal failure. Br Med J 1:209–210

    Google Scholar 

  21. Krarup T, Schwartz T, Hilsted J, Madsbad S, Verlaege O, Sestoft L (1979) Impaired response of pancreatic polypeptide to hypoglycaemia: an early sign of autonomic neuropathy in diabetics. Br Med J 2:1544–1546

    Google Scholar 

  22. Krarup T (1988) Immunoreactive gastric inhibitory polypeptide. Endocrine Rev 9:122–134

    Google Scholar 

  23. Krarup T, Nürnberg D, Mikkelsen K, et al (1990) How arterialized is blood sampled from a heated superficial hand vein? Diabetes 39 [Suppl 1]:88A (abstract)

  24. Kreymann B, Ghatei MA, Williams G, Bloom SR (1987) Glucagon-like peptide 17–36: a physiological incretin in man. Lancet 11:1300–1304

    Google Scholar 

  25. Kuku SF, Japan JB, Emmanouel DS, Zeidler A, Katz AI, Rubenstein AH (1976) Heterogeneity of plasma glucagon. Circulating components in normal subjects and patients with chronic renal failure. J Clin Invest 58:742–750

    Google Scholar 

  26. Kuzio M, Dryburgh JR, Malloy KM, Brown JC (1974) Radioimmunoassay for gastric inhibitory polypeptide. Gastroenterology 66:357–364

    Google Scholar 

  27. Landgraf R, Nusser J, Müller W, et al (1989) Fate of late complications in type 1 diabetic patients after successful pancreas-kidney transplantation. Diabetes 38 [Suppl]:33–37

    Google Scholar 

  28. Lauritzen JB, Lauritzen KB, Ege Olson M, Timmerman I (1982) Gastric inhibitory polypeptide (GIP) and insulin release in response to oral and intravenous glucose in uremic patients. Metabolism 31:1096–1099

    Google Scholar 

  29. Luzi L, Secchi A, Facchini F, et al (1990) Reduction of insulin resistance by combined kidney-pancreas-transplantation in type 1 (insulin-dependent) diabetic patients. Diabetologia 33:549–556

    Google Scholar 

  30. Mayer G, Arnold R, Feurle G, Fuchs K, Ketterer H, Track NS, Creutzfeldt (1974) Influence of feeding and sham feeding upon serum gastrin and gastric acid secretion in control subjects and duodenal ulcer patients. Scand J Gastroenterol 9:703–710

    Google Scholar 

  31. Morel P, Balakumar M, Stevens B, Kendall D, Sutherland D (1990) Long term metabolic function of pancreas transplants and comparison between endocrine and exocrine function. Diabetes 39 [Suppl 1]: 160 A (abstract)

  32. Müller WA, Faloona GR, Aguilar-Parada E, Unger RE (1970) Abnormal alpha-cell function in diabetes. Response to carbohydrate and protein ingestion. N Engl J Med 283:109–115

    Google Scholar 

  33. Mulholland MW, Debas HT (1988) Physiology and pathophysiology of gastrin: a review. Surgery 103:135–147

    Google Scholar 

  34. Nauck MA, Büsing M, Orskov C et al (1990) Preserved incretin effect after heterotopic pancreas transplantation in type 1-diabetic patients. Diabetologia 32:A 38 (abstract)

    Google Scholar 

  35. Nauck MA, Busing M, Orskov C, et al (1991) Sekretion von gastrointestinalen und Pankreas-Hormonen in Typ 1-diabetischen Patienten nach erfolgreicher kombinierter Pankreas- und Nierentransplantation. Akt Endokrinol Stoffw 12:111 (abstract)

    Google Scholar 

  36. Nerup J, Cathelineau C, Seignalet J, et al (1977) HLA and endocrine disease. In: Dausset J, Svejgaard A (eds) HLA and disease. Munksgaard, Copenhagen, pp 149–167

    Google Scholar 

  37. Ørskov C, Holst JJ (1987) Radio-immunoassays for glucagon-like peptides 1 and 2 (GLP-1 and GLP-2). Scand J Clin Lab Invest 47:165–174

    Google Scholar 

  38. Ørskov C, Jeppesen J, Madsbad S, Holst JJ (1991) Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine. J Clin Invest 87:415–423

    Google Scholar 

  39. Östman J, Bolinder J, Gunnarson R, et al (1989) Effects of pancreas transplantation on metabolic and hormonal profiles in IDDM patients. Diabetes 38 [Suppl 1]:88–93

    Google Scholar 

  40. O'Dorisio TM, Sirinek KR, Mazzaferri EL, Cataland S (1977) Renal effects on serum gastric inhibitory polypeptide (GIP). Metabolism 26:651–656

    Google Scholar 

  41. Osei K, Henry ML, O'Dorisio TM, Tesi RJ, Sommer BG, Ferguson RM (1990) Physiological and pharmacological stimulation of pancreatic islet hormone secretion in type 1 diabetic pancreas allograft recipients. Diabetes 39:1235–1342

    Google Scholar 

  42. Owyang C, Miller LJ, DiMagno EP, Brennan LA, Go VLW (1979) Gastrointestinal hormone profile in renal insufficiency. Mayo Clin Proc 54:769–773

    Google Scholar 

  43. Pagano G, Cavallo-Perin P, Cassader M, et al (1983) An in vivo and in vitro study of the mechanism of prednisoneinduced insulin resistance in healthy subjects. J Clin Invest 72:1814–1820

    Google Scholar 

  44. Paronen 1, Ala-Kaila K, Rantala I, Kainulainen H, Karvonen A-L (1991) Gastric parietal, chief, and G-cell densities in chronic renal failure. Scand J Gastroenterol 26:696–700

    Google Scholar 

  45. Pozza G, Bosi E, Secchi A, et al (1985) Metabolic control in type 1-(insulin-dependent) diabetes after pancreas transplantation. Br Med J 291:510–513

    Google Scholar 

  46. Regeur L, Faber OK, Binder C (1978) Plasma C-peptide in uraemic patients. Scand J Clin Lab Invest 38:771–775

    Google Scholar 

  47. Siegel EG, Creutzfeldt W (1989) Pancreatic transplantation or intensive insulin Baillère's Clin Gastroenterol 3:877–886

    Google Scholar 

  48. Somogyi M (1948) Studies of arteriovenous differences in blood sugar. I. Effect of alimentary hyperglycaemia on the rate of extrahepatic glucose assimilation. J Biol Chem 174:189–200

    Google Scholar 

  49. Taylor IL, Sells RA, McConnell RB, Dockray GJ (1980) Serum gastrin in patients with chronic renal failure. Gut 21:1062–1067

    Google Scholar 

  50. Theodorsson-Norheim E (1987) Friedman and Quade tests: basic computer program to perform nonoparametric twoway analysis of variance and multiple comparisons on ranks of several related samples. Comp Biol Med 17:85–99

    Google Scholar 

  51. Thompson DG, Wingate DL, Thomas M, Harrison D (1982) Gastric emptying as a determining of the oral glucose tolerance test. Gastroenterology 82:51–55

    Google Scholar 

  52. Tyden G, Brattström C, Bolinder J, et al (1989) Long-term metabolic control in recipients of segmental pancreas grafts with pancreaticoenterostomy or duct obstruction. Diabetes 38 [Suppl 1]:94–96

    Google Scholar 

  53. Unger RH (1985) Glucagon physiology and pathophysiology in the light of new advances. Diabetologia 28:574–578

    Google Scholar 

  54. Unger RH, Eisentraut AH (1969) Entero-insular axis. Arch Intern Med 123:261–266

    Google Scholar 

  55. Yovos JG, O'Dorisio TM, Pappas TN et al (1982) Effect of amino acids and gastric inhibitory polypeptide on insulin release in dogs. Am J Physiol 242:E53–58

    Google Scholar 

  56. Zukowska-Szczechowska, Grzeszczak W, Kokot F, Nieszporek T, Kusmierski S, Szkodny A (1987) Influence of type of immunosuppressive therapy on gastrin, insulin, glucagon, and pancreatic polypeptide secretion in kidney transplant patients. Transplant Proc 19:3731

    Google Scholar 

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Nauck, M.A., Büsing, M., Ørskov, C. et al. Basal and nutrient-stimulated pancreatic and gastrointestinal hormone concentrations in type-l-diabetic patients after successful combined pancreas and kidney transplantation. Clin Investig 70, 40–48 (1992). https://doi.org/10.1007/BF00422937

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