Sphingomyelin patches on pancreatic beta-cells are indicative of insulin secretory capacity.
The establishment and validation of specific markers on the surfaces of pancreatic beta-cells would have a significant impact on the development of agents that specifically target these cells for imaging and/or image-guided therapy in diabetes patient samples. We have recently described unique, cholesterol-stabilized sphingomyelin (SM) patches on the surfaces of beta-cells using the IC2 antibody. To further investigate the utility of SM patches as a unique beta-cell biomarker, we embarked on the current study to correlate the expression of this antigen with the insulin secretory capacity of beta-cells in tissue samples from patients and animals with type 1 and type 2 diabetes and compared this with samples from normal subjects. We found that the locations of SM patches were consistent with the insulin status of islets in all tissues studied. Using immunohistochemistry and staining with an IC2 antibody, we demonstrated a direct correlation between the reduced expression of SM patches and insulin production in diabetic individuals, indicating that the former could potentially serve as a functional biomarker of beta-cells. We believe that our results have significant implications for the further development of ligands with SM specificity for the non-invasive functional assessment of beta-cells and/or for targeted therapeutic delivery in diabetic patients.
Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Charlestown, MA (AK, AM).
Amol
A
Kavishwar
Anna
A
Moore
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D051381:Rats; D013109:Sphingomyelins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D007328:Insulin; D013109:Sphingomyelins
antibody; beta-cells; diabetes; sphingomyelin; surface markers