Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1996 Jun 1;97(11):2611–2618. doi: 10.1172/JCI118710

Metabolic effects of successful intraportal islet transplantation in insulin-dependent diabetes mellitus.

L Luzi 1, B J Hering 1, C Socci 1, G Raptis 1, A Battezzati 1, I Terruzzi 1, L Falqui 1, H Brandhorst 1, D Brandhorst 1, E Regalia 1, E Brambilla 1, A Secchi 1, G Perseghin 1, P Maffi 1, E Bianchi 1, V Mazzaferro 1, L Gennari 1, V Di Carlo 1, K Federlin 1, G Pozza 1, R G Bretzel 1
PMCID: PMC507348  PMID: 8647955

Abstract

The intraportal injection of human pancreatic islets has been indicated as a possible alternative to the pancreas transplant in insulin-dependent diabetic patients. Aim of the present work was to study the effect of intraportal injection of purified human islets on: (a) the basal hepatic glucose production; (b) the whole body glucose homeostasis and insulin action; and (c) the regulation of insulin secretion in insulin-dependent diabetes mellitus patients bearing a kidney transplant. 15 recipients of purified islets from cadaver donors (intraportal injection) were studied by means of the infusion of labeled glucose to quantify the hepatic glucose production. Islet transplanted patients were subdivided in two groups based on graft function and underwent: (a) a 120-min euglycemic insulin infusion (1 mU/kg/min) to assess insulin action; (b) a 120-min glucose infusion (+75 mg/di) to study the pattern of insulin secretion. Seven patients with chronic uveitis on the same immunosuppressive therapy as grafted patients, twelve healthy volunteers, and seven insulin-dependent diabetic patients with combined pancreas and kidney transplantation were also studied as control groups. Islet transplanted patients have: (a) a higher basal hepatic glucose production (HGP: 5.1 +/- 1.4 mg/kg/ min; P < 0.05 with respect to all other groups) if without graft function, and a normal HGP (2.4 +/- 0.2 mg/kg/min) with a functioning graft; (b) a defective tissue glucose disposal (3.9 +/- 0.5 mg/kg/min in patients without islet function and 5.3 +/- 0.4 mg/kg/min in patients with islet function) with respect to normals (P < 0.01 for both comparisons); (c) a blunted first phase insulin peak and a similar second phase secretion with respect to controls. In conclusion, in spite of the persistence of an abnormal pattern of insulin secretion, successful intraportal islet graft normalizes the basal HGP and improves total tissue glucose disposal in insulin-dependent diabetes mellitus.

Full Text

The Full Text of this article is available as a PDF (197.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Battezzati A., Luzi L., Perseghin G., Bianchi E., Spotti D., Secchi A., Vergani S., Di Carlo V., Pozza G. Persistence of counter-regulatory abnormalities in insulin-dependent diabetes mellitus after pancreas transplantation. Eur J Clin Invest. 1994 Nov;24(11):751–758. doi: 10.1111/j.1365-2362.1994.tb01072.x. [DOI] [PubMed] [Google Scholar]
  2. Cottrell D. A., Henry M. L., O'Dorisio T. M., Tesi R. J., Ferguson R. M., Osei K. Hypoglycemia after successful pancreas transplantation in type I diabetic patients. Diabetes Care. 1991 Nov;14(11):1111–1113. doi: 10.2337/diacare.14.11.1111. [DOI] [PubMed] [Google Scholar]
  3. Elahi D., Clark B. A., McAloon-Dyke M., Wong G., Brown R., Shapiro M., Minaker K. L., Flanagan T. L., Pruett T., Gingerich R. Islet cell responses to glucose in human transplanted pancreas. Am J Physiol. 1991 Dec;261(6 Pt 1):E800–E808. doi: 10.1152/ajpendo.1991.261.6.E800. [DOI] [PubMed] [Google Scholar]
  4. Groth C. G., Collste H., Lundgren G., Wilczek H., Klintmalm G., Ringdén O., Gunnarsson R., Ostman J. Successful outcome of segmental human pancreatic transplantation with enteric exocrine diversion after modifications in technique. Lancet. 1982 Sep 4;2(8297):522–524. doi: 10.1016/s0140-6736(82)90601-8. [DOI] [PubMed] [Google Scholar]
  5. Havel P. J., Taborsky G. J., Jr The contribution of the autonomic nervous system to changes of glucagon and insulin secretion during hypoglycemic stress. Endocr Rev. 1989 Aug;10(3):332–350. doi: 10.1210/edrv-10-3-332. [DOI] [PubMed] [Google Scholar]
  6. Hosker J. P., Burnett M. A., Matthews D. R., Turner R. C. Prednisolone enhances beta-cell function independently of ambient glycemic levels in type II diabetes. Metabolism. 1993 Sep;42(9):1116–1120. doi: 10.1016/0026-0495(93)90268-s. [DOI] [PubMed] [Google Scholar]
  7. Katz H., Homan M., Velosa J., Robertson P., Rizza R. Effects of pancreas transplantation on postprandial glucose metabolism. N Engl J Med. 1991 Oct 31;325(18):1278–1283. doi: 10.1056/NEJM199110313251804. [DOI] [PubMed] [Google Scholar]
  8. Laube F., Hahn H. J. Effect of cyclosporin-A on insulin secretion in vitro. Horm Metab Res. 1985 Jan;17(1):43–44. doi: 10.1055/s-2007-1013445. [DOI] [PubMed] [Google Scholar]
  9. Luzi L., Barrett E. J., Groop L. C., Ferrannini E., DeFronzo R. A. Metabolic effects of low-dose insulin therapy on glucose metabolism in diabetic ketoacidosis. Diabetes. 1988 Nov;37(11):1470–1477. doi: 10.2337/diab.37.11.1470. [DOI] [PubMed] [Google Scholar]
  10. Luzi L., Battezzati A., Perseghin G., Bianchi E., Vergani S., Secchi A., La Rocca E., Staudacher C., Spotti D., Ferrari G. Lack of feedback inhibition of insulin secretion in denervated human pancreas. Diabetes. 1992 Dec;41(12):1632–1639. doi: 10.2337/diab.41.12.1632. [DOI] [PubMed] [Google Scholar]
  11. Luzi L., DeFronzo R. A. Effect of loss of first-phase insulin secretion on hepatic glucose production and tissue glucose disposal in humans. Am J Physiol. 1989 Aug;257(2 Pt 1):E241–E246. doi: 10.1152/ajpendo.1989.257.2.E241. [DOI] [PubMed] [Google Scholar]
  12. Luzi L., Secchi A., Facchini F., Battezzati A., Staudacher C., Spotti D., Castoldi R., Ferrari G., Di Carlo V., Pozza G. Reduction of insulin resistance by combined kidney-pancreas transplantation in type 1 (insulin-dependent) diabetic patients. Diabetologia. 1990 Sep;33(9):549–556. doi: 10.1007/BF00404143. [DOI] [PubMed] [Google Scholar]
  13. May R. C., Clark A. S., Goheer M. A., Mitch W. E. Specific defects in insulin-mediated muscle metabolism in acute uremia. Kidney Int. 1985 Sep;28(3):490–497. doi: 10.1038/ki.1985.155. [DOI] [PubMed] [Google Scholar]
  14. Mitrakou A., Kelley D., Mokan M., Veneman T., Pangburn T., Reilly J., Gerich J. Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. N Engl J Med. 1992 Jan 2;326(1):22–29. doi: 10.1056/NEJM199201023260104. [DOI] [PubMed] [Google Scholar]
  15. Nielsen J. H., Mandrup-Poulsen T., Nerup J. Direct effects of cyclosporin A on human pancreatic beta-cells. Diabetes. 1986 Sep;35(9):1049–1052. doi: 10.2337/diab.35.9.1049. [DOI] [PubMed] [Google Scholar]
  16. Robertson R. P. Seminars in medicine of the Beth Israel Hospital, Boston: Pancreatic and islet transplantation for diabetes--cures or curiosities? N Engl J Med. 1992 Dec 24;327(26):1861–1868. doi: 10.1056/NEJM199212243272607. [DOI] [PubMed] [Google Scholar]
  17. Scopsi L., Andreola S., Socci C., Bertuzzi F., Di Carlo V., Pozza G., Rilke F., Gennari L., Colella G., Regalia E. Immunocytochemical detection and characterization of intrahepatic human pancreatic islets after combined liver-islet allotransplantation. Cell Transplant. 1994 Nov-Dec;3(6):499–508. doi: 10.1177/096368979400300607. [DOI] [PubMed] [Google Scholar]
  18. Secchi A., Dubernard J. M., La Rocca E., LeFrancois N., Melandri M., Martin X., Touraine J. L., Traeger J., Pozza G. Endocrinometabolic effects of whole versus segmental pancreas allotransplantation in diabetic patients--a two-year follow-up. Transplantation. 1991 Mar;51(3):625–629. doi: 10.1097/00007890-199103000-00016. [DOI] [PubMed] [Google Scholar]
  19. Yki-Järvinen H., Koivisto V. A. Continuous subcutaneous insulin infusion therapy decreases insulin resistance in type 1 diabetes. J Clin Endocrinol Metab. 1984 Apr;58(4):659–666. doi: 10.1210/jcem-58-4-659. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES