![]() At the end of the study period, all mice in all groups were normoglycemic. In contrast, mice transplanted with 2000 IEQs from Donor 3 and treated with alogliptin showed a significant acceleration in the lowering of blood glucose levels relative to mice receiving vehicle alone. Normoglycemia was restored within 1 week for diabetic mice transplanted with 2000 IEQs from both Donors 1 and 2, regardless of treatment status ( Figure 1A). Daily alogliptin (or vehicle control) treatments were started at day 1 post-transplant. The islet donor characteristics are shown in Table 1. Three independent studies were performed with human islets from three different donors. After diabetes was confirmed, mice were given subcutaneous insulin implants to maintain the health of the animals until human islets were available for transplant. Normoglycemic NSG mice (blood glucose <150 mg/dL) were made chemically diabetic with STZ treatment. The goal of this study was to utilize STZ-induced diabetic NSG mice transplanted with human pancreatic islets to determine the ability of alogliptin to enhance human beta cell function and proliferation. 17 We hypothesized that alogliptin treatment of diabetic immunodeficient mice engrafted with human islets will measurably enhance the proliferation and insulin secretory function of human beta cells in an in vivo setting. 15 ā 17 Alogliptin was found to improve glycemic control in patients with poorly controlled diabetes as evidenced by reduced fasting blood glucose and hemoglobin A1c levels. ![]() Recently, a new DPP-4 inhibitor, alogliptin, has been developed 14 and its safety and efficacy in treating type 2 diabetes (T2D) patients is being investigated. An alternative method to investigate human islet function in vivo is to transplant human islets into streptozotocin (STZ)-induced diabetic NOD- scid IL2rĪ³ null (NSG) mice. 9 ā 11 However, human islet function remains difficult to assess directly due to inaccessibility of relevant tissues, as well as inherent variability between patients. 6 ā 8 In clinical trials with agents that block GLP-1 degradation, such as dipeptidyl-peptidase-4 (DPP-4) inhibitors, fasting and postprandial glucose levels of patients are also lowered, consistent with improved pancreatic beta cell function. 5 Glycemic control of patients taking metformin or sulfonylurea was also improved in conjunction with GLP-1 receptor agonists. 1, 2 In clinical trials with type 2 diabetic patients, GLP-1 receptor agonists lowered both fasting and postprandial glucose concentrations, 3, 4 although no improvement (as measured by C-peptide secretion) was observed in patients with long-standing type 1 diabetes. Glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists increase glucosedependent insulin secretion, beta cell viability, and activate proliferative pathways that lead to increased beta cell mass in rodents.
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