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Diabetologia

Erschienen in:

01.08.2006 | Article

Direct evidence of attempted beta cell regeneration in an 89-year-old patient with recent-onset type 1 diabetes

verfasst von: J. J. Meier, J. C. Lin, A. E. Butler, R. Galasso, D. S. Martinez, P. C. Butler

Erschienen in: Diabetologia | Ausgabe 8/2006

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Abstract

Aims/hypothesis

We investigated whether there was evidence of attempted beta cell regeneration in the pancreas obtained from a patient with recent-onset type 1 diabetes, and if so by what mechanism this occurred.

Subjects, materials and methods

We examined pancreas tissue from a lean 89-year-old patient (BMI 18.0 kg/m²) with recent-onset type 1 diabetes who had had a distal pancreatectomy to remove a low-grade pancreatic intraepithelial neoplasia.

Results

In the tumour-free tissue, the fractional beta cell area was 0.54±0.2% of pancreas area (about one-third of that in non-diabetic humans). CD3-positive T lymphocytes and macrophages had infiltrated the majority of the islets. Subclassification of the T cell population revealed a predominance of CD8-positive cells over CD4-positive cells. Beta cell apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling [TUNEL] staining) was greatly increased, consistent with ongoing immune-mediated beta cell destruction. There was also a marked increase (more than ∼100-fold) in the frequency of beta cell replication (0.69±0.15% Ki67-positive beta cells) in all blocks examined.

Conclusions/interpretation

The present report provides direct evidence of attempted beta cell regeneration through the mechanism of beta cell replication in a case of newly diagnosed type 1 diabetes, and affirms that beta cell apoptosis is an important mechanism for beta cell loss in type 1 diabetes.

Atkinson MA, Eisenbarth GS (2001) Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 358:221–229PubMedCrossRef

Kloppel G, Drenck CR, Oberholzer M, Heitz PU (1984) Morphometric evidence for a striking B-cell reduction at the clinical onset of type 1 diabetes. Virchows Arch A Pathol Anat Histopathol 403:441–452PubMedCrossRef

Gale EA (2001) The discovery of type 1 diabetes. Diabetes 50:217–226PubMedCrossRef

Gepts W, De Mey J (1978) Islet cell survival determined by morphology. An immunocytochemical study of the islets of Langerhans in juvenile diabetes mellitus. Diabetes 27(Suppl 1):251–261PubMed

Lohr M, Kloppel G (1987) Residual insulin positivity and pancreatic atrophy in relation to duration of chronic type 1 (insulin-dependent) diabetes mellitus and microangiopathy. Diabetologia 30:757–762PubMedCrossRef

Pipeleers D, Ling Z (1992) Pancreatic beta cells in insulin-dependent diabetes. Diabetes Metab Rev 8:209–227PubMedCrossRef

Meier JJ, Bhushan A, Butler AE, Rizza RA, Butler PC (2005) Sustained beta-cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration? Diabetologia 48:2221–2228PubMedCrossRef

Kurrer MO, Pakala SV, Hanson HL, Katz JD (1997) Beta cell apoptosis in T cell-mediated autoimmune diabetes. Proc Natl Acad Sci USA 94:213–218PubMedCrossRef

Chatenoud L, Thervet E, Primo J, Bach JF (1994) Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc Natl Acad Sci USA 91:123–127PubMedCrossRef

10.

Butler AE, Janson J, Bonner-Weir S et al (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52:102–210PubMedCrossRef

11.

Yoon KH, Ko SH, Cho JH et al (2003) Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab 88:2300–2308PubMedCrossRef

12.

Melton LJ 3rd, Palumbo PJ, Chu CP (1983) Incidence of diabetes mellitus by clinical type. Diabetes Care 6:75–86PubMedCrossRef

13.

Kassem SA, Ariel I, Thornton PS, Scheimberg I, Glaser B (2000) Beta-cell proliferation and apoptosis in the developing normal human pancreas and in hyperinsulinism of infancy. Diabetes 49:1233–1325CrossRef

14.

Bouwens L, Pipeleers DG (1998) Extra-insular beta cells associated with ductules are frequent in adult human pancreas. Diabetologia 41:629–633PubMedCrossRef

15.

Bouwens L, Rooman I (2005) Regulation of pancreatic beta-cell mass. Physiol Rev 85:1255–1270PubMedCrossRef

16.

Warren S, Root HF (1925) The pathology of diabetes, with special reference to pancreatic regeneration. Am J Pathol 1:415–430

17.

Dor Y, Brown J, Martinez OI, Melton DA (2004) Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429:41–46PubMedCrossRef

18.

Georgia S, Bhushan A (2004) Beta cell replication is the primary mechanism for maintaining postnatal beta cell mass. J Clin Invest 114:963–968PubMed

19.

Tsai EB, Sherry NA, Palmer JP, Herold KC (2006) The rise and fall of insulin secretion in type 1 diabetes mellitus. Diabetologia 49:261–270PubMedCrossRef

20.

Meier JJ, Ritzel RA, Maedler K, Gurlo T, Butler PC (2005) Increased vulnerability of newly forming beta-cells to cytokine-induced cell death. Diabetologia 49:83–89PubMedCrossRef

21.

Maedler K, Schumann DM, Iwakura Y, Donath MY (2005) The physiological role of interleukin-1beta is mediated by IL-1Ra secretion of human pancreatic islets. Diabetes 54(Suppl 1):A387 (Abstract)

22.

Sreenan S, Pick AJ, Levisetti M et al (1999) Increased beta-cell proliferation and reduced mass before diabetes onset in the nonobese diabetic mouse. Diabetes 48:989–996PubMedCrossRef

23.

Pour PM, Schmied BM, Ulrich AB et al (2001) Abnormal differentiation of islet cells in pancreatic cancer. Pancreatology 1:110–116PubMedCrossRef

24.

Chari ST, Zapiach M, Yadav D, Rizza RA (2005) Beta-cell function and insulin resistance evaluated by HOMA in pancreatic cancer subjects with varying degrees of glucose intolerance. Pancreatology 5:229–233PubMedCrossRef

25.

Zhang ZL, Constantinou D, Mandel TE, Georgiou HM (1994) Lymphocyte subsets in thymus and peripheral lymphoid tissues of aging and diabetic NOD mice. Autoimmunity 17:41–48PubMedCrossRef

26.

Foulis AK, Stewart JA (1984) The pancreas in recent-onset type 1 (insulin-dependent) diabetes mellitus: insulin content of islets, insulitis and associated changes in the exocrine acinar tissue. Diabetologia 26:456–461PubMedCrossRef

27.

Meier JJ, Bhushan A, Butler PC (2006) The potential for stem cell therapy in diabetes. Pediatr Res 59:65R–73RPubMedCrossRef

28.

Chong AS, Shen J, Tao J et al (2006) Reversal of diabetes in non-obese diabetic mice without spleen cell-derived beta cell regeneration. Science 311:1774–1775PubMedCrossRef

29.

Nishio J, Gaglia JL, Turvey SE et al. (2006) Islet recovery and reversal of murine type 1 diabetes in the absence of any infused spleen cell contribution. Science 311:1775–1778PubMedCrossRef

30.

Suri A, Calderon B, Esparza TJ et al (2006) Immunological reversal of autoimmune diabetes without hematopoietic replacement of beta cells. Science 311:1778–1780PubMedCrossRef

31.

Keymeulen B, Vandemeulebroucke E, Ziegler AG et al (2005) Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med 352:2598–2608PubMedCrossRef

Titel: Direct evidence of attempted beta cell regeneration in an 89-year-old patient with recent-onset type 1 diabetes
verfasst von: J. J. Meier
J. C. Lin
A. E. Butler
R. Galasso
D. S. Martinez
P. C. Butler
Publikationsdatum: 01.08.2006
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 8/2006
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-006-0308-2

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Abstract

Aims/hypothesis

Subjects, materials and methods

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