Effects of autoimmunity and immune therapy on [beta]-cell turnover in type 1 diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 55; no. 12; pp. 3238 - 3245
• Main Authors: Sherry, Nicole A, Kushner, Jake A, Glandt, Mariela, Kitamura, Tadahiro, Brillantes, Anne-Marie B, Herold, Kevan C
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01.12.2006
• Subjects: Care and treatment; Cells; Diabetes; Diagnosis; Glucose; Health aspects; Hyperglycemia; Hyperplasia; Insulin; Insulin resistance; Metabolism; Peptides; Type 1 diabetes; Veins & arteries
• ISSN: 0012-1797; 1939-327X

[beta]-Cell mass can expand in response to demand: during pregnancy, in the setting of insulin resistance, or after pancreatectomy. It is not known whether similar [beta]-cell hyperplasia occurs following immune therapy of autoimmune diabetes, but the clinical remission soon after diagnosis and the results of recent immune therapy studies suggest that [beta]-cell recovery is possible. We studied changes in [beta]-cell replication, mass, and apoptosis in NOD mice during progression to overt diabetes and following immune therapy with anti-CD3 monoclonal antibodies (mAbs) or immune regulatory T-cells (Tregs). [beta]-Cell replication increases in pre-diabetic mice, after adoptive transfer of diabetes with increasing islet inflammation but before an increase in blood glucose concentration or a significant decrease in [beta]-cell mass. The pathogenic cells are responsible for increasing [beta]-cell replication because replication was reduced during diabetes remission induced by anti-CD3 mAb or Tregs. [beta]-Cell replication stimulated by the initial inflammatory infiltrate results in increased production of new [beta]-cells after immune therapy and increased [beta]-cell area, but the majority of this increased [beta]-cell area represents regranulated [beta]-cells rather than newly produced cells. We conclude that [beta]-cell replication is closely linked to the islet inflammatory process. A significant proportion of degranulated [beta]-cells remain, at the time of diagnosis of diabetes, that can recover after metabolic correction of hyperglycemia. Correction of the [beta]-cell loss in type 1 diabetes will, therefore, require strategies that target both the immunologic and cellular mechanisms that destroy and maintain [beta]-cell mass.