title: Effect of diabetic state on co-localization of substance P and serotonin in the gut in animal models.
abstract: Changes in the numbers of serotonin- and substance P-immunoreactive (IR) cells occur in several animal models of diabetes. It is not known, however, whether these changes are a result of actual cell loss or are caused by modified gene expression in cells showing co-localization of serotonin and substance P. The pattern of mono- and co-expression of serotonin, as well as of substance P, was therefore investigated in gastrointestinal endocrine cells from animal models of human type 1 and type 2 diabetes, namely non-obese diabetic (NOD) and obese diabetic (ob/ob) mice. Immunocytochemical staining by the avidin-biotin complex method was performed for computerized image analysis of each cell type, and by immunofluorescence double staining to study co-localization. Tissues from antrum, proximal duodenum and distal colon were investigated. Co-localization of serotonin- and substance P-IR was found in all investigated parts of the gut. In antrum, substance P immunoreactivity was found exclusively in serotonin-IR cells. In both NOD and ob/ob mice there was a reduced number of substance P-IR cells, but an unchanged serotonin-IR cell count, which thus tallies with a shut-off of substance P expression in antral enterochromaffin cells. In duodenum, both diabetes models showed a decreased number of serotonin-IR cells. Furthermore there was a decreased number of substance P-IR cells in the type 2 model. The proportion of serotonin-IR cells showing substance P-immuno-reactivity was decreased in both diabetic models, thus indicating a shut-off of substance P-gene expression. However, this does not fully explain the changes in duodenum, but the diabetic state probably affects the number of mono-expressed cells as well. In colon, no change was found in diabetic mice regarding co-localization of substance P and serotonin. However, pre-diabetic NOD mice showed a decreased proportion of substance P in serotonin-IR cells, which might be explained by the increased number of serotonin-IR cells, combined with an unchanged number of substance P-IR cells. In conclusion, diabetic animal models of both type 1 and type 2 appear to have a combination of decreased expression of substance P in serotonin-IR cells of both antrum and duodenum, as well as a change in the number of mono-expressed cells. The pattern in colon, on the other hand, seems to be unaffected.
authors.affiliation: Department of Medicine, University Hospital, Umeå, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Spångéus
authors.forename: S
authors.initials: S
authors.lastname: Forsgren
authors.forename: M
authors.initials: M
authors.lastname: El-Salhy
mesh_terms: D000818:Animals; D003106:Colon / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D004064:Digestive System / Q000378:metabolism*; D004386:Duodenum / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D019858:Enteroendocrine Cells / Q000378:metabolism*; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008820:Mice, Obese; D011236:Prediabetic State / Q000378:metabolism / Q000473:pathology; D011706:Pyloric Antrum / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D012701:Serotonin / Q000032:analysis*; D013373:Substance P / Q000032:analysis
chemical_list: D012701:Serotonin; D013373:Substance P