A 50-year-old man developed a pancreatic islet tumor with liver metastases. High levels of islet amyloid polypeptide (IAPP) were recorded in plasma-35,000 pmol/L-concomitant with the occurrence of type II diabetes mellitus (the clinical syndrome has recently been described in detail) [25]. Light microscopically, the tumor contained considerable amounts of amyloid and displayed IAPP immunoreactivity both in the tumor cells and in the amyloid stroma. Electron-microscopical examination of the liver metastases showed presence of round secretory granules in the tumor cells. The granules were immunoreactive to chromogranin A and B and IAPP but not to insulin. The amyloid deposits were mainly accumulated in the extracellular spaces but were also present in the tumor cell cytoplasm. The intracellufar amyloid fibrils were, as revealed by immunogold labeling, IAPP immunoreactive and seemed to emerge from the secretory granules in the shape of radiating threads. The results show that in this particular case, the amyloid formation started already at the intracellular level and in close proximity to the lAPP-storing secretory granules. The findings may have some significance for understanding the development of pancreatic islet B-cell-related amyloidosis in type II diabetes mellitus.

Pancreatic islet transplantation into the liver is an effective treatment for type 1 diabetes but has some critical limitations. The subcutaneous site is a potential alternative transplant site, requiring minimally invasive procedures and allowing frequent graft monitoring; however, hypoxia is a major drawback. Our previous study without scaffolding demonstrated post-transplant graft aggregation in the subcutaneous site, which theoretically exacerbates lethal intra-graft hypoxia. In this study, we introduce a clinically applicable subcutaneous islet transplantation platform using a biodegradable Vicryl mesh scaffold to prevent aggregation in a diabetic rat model. Islets were sandwiched between layers of clinically proven Vicryl mesh within thrombin-fibrin gel. In vitro, the mesh prevented islet aggregation and intra-islet hypoxia, which significantly improved islet viability. In vivo rat syngeneic islet transplantations into a prevascularized subcutaneous pocket demonstrated that the mesh significantly enhanced engraftment, as measured by assays for graft survival and function. Histological examination at 6 weeks showed well-vascularized grafts sandwiched in a flat shape between the mesh layers. The biodegradable mesh was fully absorbed by three months, which alleviated chronic foreign body reaction and fibrosis, and supported long-term graft maintenance. This simple graft shape modification approach is an effective and clinically applicable strategy for improved subcutaneous islet transplantation.

(1) Background: Disruption of insulin production by native or transplanted pancreatic islets caused by auto/allo-immunity leads to hyperglycemia, a serious health condition and important therapeutic challenge due to the lifelong need for exogeneous insulin administration. Early metabolic biomarkers can prompt timely interventions to preserve islet function, but reliable biomarkers are currently lacking. We explored the feasibility of \"localized metabolomics\" where initial biomarker discovery is made in aqueous humor samples for further validation in the circulation. (2) Methods: We conducted non-targeted metabolomic studies in parallel aqueous humor and plasma samples from diabetic and nondiabetic mice. Metabolite levels and associated pathways were compared in both compartments as well as to an earlier longitudinal dataset in hyperglycemia-progressor versus non-progressor non-obese diabetic (NOD) mice. (3) Results: We confirmed that aqueous humor samples can be used to assess metabolite levels. About half of the identified metabolites had well-correlated levels in the aqueous humor and plasma. Several plasma metabolites were significantly different between diabetic and nondiabetic animals and between males and females, and many of them were correlated with the aqueous humor. (4) Conclusions: This study provides proof-of-concept evidence that aqueous humor samples enriched with islet-related metabolites and representative of the immediate islet microenvironment following intraocular islet transplant can be used to assess metabolic changes that could otherwise be overlooked in the general circulation. The findings support localized metabolomics, with and without intraocular islet transplant, to identify biomarkers associated with diabetes and islet allograft rejection.

Ablation, transplantation and culture experiments were used to determine the respective roles of the pancreatic dorsal and ventral anlagen in the formation of the endocrine cells. Three successive waves of endocrine formation occur in the pancreas of Bufo bufo at three developmental stages (III6, IV1 and IV2). Each wave is derived from a different source: the first originates from the dorsal anlage, the second from the exocrine tissue of the cortex of the pancreas and the third from the pancreatic duct. Each generation of islets has a specific composition of different cell types. The first wave is only composed of insulin islets; the second wave gives rise to single insulin, glucagon and somatostatin cells; while the third wave generates single cells synthesizing one of the three hormones, homogeneous islets of insulin cells, rare glucagon islets and heterogeneous islets containing insulin cells in the centre and a few glucagon or somatostatin cells at the periphery.