Spontaneous recovery from established type 1 diabetes (T1D) is so rare that only one well-documented case has ever been described in an adult, and in that case recovery resulted from an insulin-secreting tumor, not regeneration of the patient’s normal beta-cells. Therefore, when we saw a 50 year old man at UCSF with T1D who got off insulin (Patient 36300562), we investigated the cause. He had a pancreatic neuroendocrine tumor (PNET), but it was not producing insulin. Instead, in the few islets in his pancreas that still contained beta-cells, those beta-cells were proliferating at rates far exceeding anything previously reported in humans, suggesting that PNETs may produce factors that can promote human beta-cell regeneration. We also found alpha-cells of Patient 36300562 were producing ghrelin, suggesting that gut hormone expression in islet cells may be a characteristic of the T1D pancreas. SPECIFIC AIM 1: Characterize the expression of ghrelin in the pancreatic islets of patients with and without diabetes. We will perform immunostaining assays for ghrelin in sections of normal and T1D pancreas samples from the nPOD. We will also examine the expression of PYY and somatostatin to gain a better understanding of how hormone gene expression may be different in the islet of T1D patients. These studies will help clarify whether the expression of ghrelin in the alpha-cells of Patient 363000562, who had T1D, is a consequence of the PNET or T1D. These studies will also add to our knowledge of the T1D pancreas phenotype. SPECIFIC AIM 2: Characterize the beta-cell phenotypes in patients with PNET. The high beta-cell proliferation rate and T1D recovery of Patient 36300562 suggests that PNETs may produce factors that can promote human beta-cell regeneration. We will therefore also examine markers of beta-cell proliferation (Ki67) and death (TUNEL). These studies will help confirm the beta cell phenotype of Patient 36300562, and may help justify additional studies to identify novel factors from PNETs that promote human beta-cell regeneration.