Impaired β-Cell Function in Type 1 Diabetes after Islet Transplantation

What is it about?

The study evaluated the function of islet transplantation in five subjects at three months and four subjects at twelve months. C-peptide responses were significantly impaired in both transplant groups when compared with healthy control subjects after intravenous glucose, an orally consumed meal, and intravenous arginine. A glucose-potentiated arginine test demonstrated significant impairments in the glucose-potentiation slope and the maximal response to arginine, a measure of β-cell secretory capacity. These results suggest that a low engrafted β-cell mass may account for the functional defects observed after islet transplantation. The study found impaired first-phase secretory responses to intravenous glucose and a blunted secretory response to intravenous arginine, confirming previous reports of absent first-phase insulin secretion in response to glucose and a relatively greater β-cell secretory response to arginine compared with glucose following transplantation. The results are consistent with animal models of β-cell reduction, including rats treated by either streptozotocin administration or partial pancreatectomy.

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Why is it important?

This research is important because it provides new insights into the β-cell function that follows human islet transplantation. The study found markedly impaired first-phase secretory response to intravenous glucose, blunted secretory response to intravenous arginine, and blunted and delayed secretory response to an orally consumed meal. These findings suggest that there is an insufficient β-cell mass following even ""successful"" islet transplantation, as indicated by the markedly impaired arginine-stimulated C-peptide (AR max), a measure of β-cell secretory capacity. The results also indicate that a low engrafted β-cell mass may account for the functional defects observed after islet transplantation. These findings have implications for improving the engraftment and survival of transplanted islets, enhancing the function of the existing β-cell mass, and developing immunosuppressive strategies that minimize the use of diabetogenic drugs. Key Takeaways: 1. Islet transplantation can provide metabolic stability for patients with type 1 diabetes, but more than one donor pancreas is usually required to achieve insulin independence. 2. The study found impaired β-cell function in subjects who received islet transplantation, suggesting an insufficient β-cell mass following successful islet transplantation. 3. The results have implications for improving the engraftment and survival of transplanted islets, enhancing the function of the existing β-cell mass, and developing immunosuppressive strategies that minimize the use of diabetogenic drugs.