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

• Published in: Diabetologia Vol. 49; no. 8; pp. 1838 - 1844
• Main Authors: Meier, J. J., Lin, J. C., Butler, A. E., Galasso, R., Martinez, D. S., Butler, P. C.
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.08.2006; Springer Nature B.V
• Subjects: Age of Onset; Aged, 80 and over; Biological and medical sciences; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Humans; Islets of Langerhans - pathology; Islets of Langerhans - physiopathology; Islets of Langerhans - secretion; Male; Medical sciences; Pancreatectomy; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - surgery; Regeneration; Endocrinopathy; Human; Immunopathology; Langerhans islet; Autoimmune disease; Beta cell replication; Beta cells; Regeneration; Cell death; Type 1 diabetes; Beta cell apoptosis; Replication; β Cell; Islets of Langerhans; Endocrine pancreas; Apoptosis
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-006-0308-2

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. We examined pancreas tissue from a lean 89-year-old patient (BMI 18.0 kg/m(2)) with recent-onset type 1 diabetes who had had a distal pancreatectomy to remove a low-grade pancreatic intraepithelial neoplasia. 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 approximately 100-fold) in the frequency of beta cell replication (0.69+/-0.15% Ki67-positive beta cells) in all blocks examined. 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.