Limits...
Activated pancreatic stellate cells can impair pancreatic islet function in mice.

Zang G, Sandberg M, Carlsson PO, Welsh N, Jansson L, Barbu A - Ups. J. Med. Sci. (2015)

Bottom Line: Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets.In islet transplants they were found mainly in the graft periphery.Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Cell Biology, Uppsala University , Uppsala , Sweden.

ABSTRACT

Background: Pancreatic or islet fibrosis is often associated with activated pancreatic stellate cells (PSCs). PSCs are considered not only to promote fibrosis, but also to be associated with glucose intolerance in some diseases. We therefore evaluated morphological and functional relationships between islets and PSCs in the normal mouse pancreas and transplanted islets.

Methods: Immunohistochemistry was used to map the presence of PSCs in the normal mouse pancreas and islets implanted under the renal capsule. We isolated and cultured mouse PSCs and characterized them morphologically by immunofluorescence staining. Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets.

Results: PSCs were scattered throughout the pancreas, with occasional cells within the islets, particularly in the islet capsule. In islet transplants they were found mainly in the graft periphery. Cultured PSCs became functionally activated and produced several cytokines. Throughout the culture period they linearly increased their production of interleukin-6 and mammalian keratinocyte-derived chemokine. PSC cytokine production was not affected by acute hyperglycemia. Syngeneic islets co-cultured with PSCs for 24-48 h increased their insulin release and lowered their insulin content. However, short-term insulin release in batch-type incubations was unaffected after 48 h of co-culture. Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days.

Conclusion: Activated PSCs may contribute to impaired islet endocrine function seen in exocrine pancreatitis and in islet fibrosis associated with some cases of type 2 diabetes.

No MeSH data available.


Related in: MedlinePlus

Desmin staining (brown) of endogenous pancreas and implanted mouse pancreatic islets. Transplants were implanted under the renal capsule 4 weeks before study. A: There are stellate cells within the exocrine parenchyma and within the islets in the endogenous gland, with especially prominent cells seen in the islet capsule. B: Stellate cells are also associated with the capsule overlying the transplant. A few scattered cells are also seen within the graft. Scale bars 100 μm. C: The fractional area of desmin-positive cells in exocrine pancreas and within (intra-islet) or around (peri-insular) endogenous islets and transplanted islets. Values are means ± SEM for 5–6 experiments.** P < 0.01, and *** P < 0.001 compared with the value for endogenous islets (Student’s t test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4526872&req=5

Figure 1: Desmin staining (brown) of endogenous pancreas and implanted mouse pancreatic islets. Transplants were implanted under the renal capsule 4 weeks before study. A: There are stellate cells within the exocrine parenchyma and within the islets in the endogenous gland, with especially prominent cells seen in the islet capsule. B: Stellate cells are also associated with the capsule overlying the transplant. A few scattered cells are also seen within the graft. Scale bars 100 μm. C: The fractional area of desmin-positive cells in exocrine pancreas and within (intra-islet) or around (peri-insular) endogenous islets and transplanted islets. Values are means ± SEM for 5–6 experiments.** P < 0.01, and *** P < 0.001 compared with the value for endogenous islets (Student’s t test).

Mentions: Desmin-positive PSCs were found throughout the mouse pancreas, associated with intra- and interlobular connective tissue in the exocrine parenchyma but also within and surrounding the islets (Figure 1A). In islets syngeneically transplanted under the renal capsule, scattered desmin-positive cells were found, especially in the periphery of the grafts. They were mainly located in the connective tissue capsule overlying the endocrine cell aggregates (Figure 1B).


Activated pancreatic stellate cells can impair pancreatic islet function in mice.

Zang G, Sandberg M, Carlsson PO, Welsh N, Jansson L, Barbu A - Ups. J. Med. Sci. (2015)

Desmin staining (brown) of endogenous pancreas and implanted mouse pancreatic islets. Transplants were implanted under the renal capsule 4 weeks before study. A: There are stellate cells within the exocrine parenchyma and within the islets in the endogenous gland, with especially prominent cells seen in the islet capsule. B: Stellate cells are also associated with the capsule overlying the transplant. A few scattered cells are also seen within the graft. Scale bars 100 μm. C: The fractional area of desmin-positive cells in exocrine pancreas and within (intra-islet) or around (peri-insular) endogenous islets and transplanted islets. Values are means ± SEM for 5–6 experiments.** P < 0.01, and *** P < 0.001 compared with the value for endogenous islets (Student’s t test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526872&req=5

Figure 1: Desmin staining (brown) of endogenous pancreas and implanted mouse pancreatic islets. Transplants were implanted under the renal capsule 4 weeks before study. A: There are stellate cells within the exocrine parenchyma and within the islets in the endogenous gland, with especially prominent cells seen in the islet capsule. B: Stellate cells are also associated with the capsule overlying the transplant. A few scattered cells are also seen within the graft. Scale bars 100 μm. C: The fractional area of desmin-positive cells in exocrine pancreas and within (intra-islet) or around (peri-insular) endogenous islets and transplanted islets. Values are means ± SEM for 5–6 experiments.** P < 0.01, and *** P < 0.001 compared with the value for endogenous islets (Student’s t test).
Mentions: Desmin-positive PSCs were found throughout the mouse pancreas, associated with intra- and interlobular connective tissue in the exocrine parenchyma but also within and surrounding the islets (Figure 1A). In islets syngeneically transplanted under the renal capsule, scattered desmin-positive cells were found, especially in the periphery of the grafts. They were mainly located in the connective tissue capsule overlying the endocrine cell aggregates (Figure 1B).

Bottom Line: Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets.In islet transplants they were found mainly in the graft periphery.Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Cell Biology, Uppsala University , Uppsala , Sweden.

ABSTRACT

Background: Pancreatic or islet fibrosis is often associated with activated pancreatic stellate cells (PSCs). PSCs are considered not only to promote fibrosis, but also to be associated with glucose intolerance in some diseases. We therefore evaluated morphological and functional relationships between islets and PSCs in the normal mouse pancreas and transplanted islets.

Methods: Immunohistochemistry was used to map the presence of PSCs in the normal mouse pancreas and islets implanted under the renal capsule. We isolated and cultured mouse PSCs and characterized them morphologically by immunofluorescence staining. Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets.

Results: PSCs were scattered throughout the pancreas, with occasional cells within the islets, particularly in the islet capsule. In islet transplants they were found mainly in the graft periphery. Cultured PSCs became functionally activated and produced several cytokines. Throughout the culture period they linearly increased their production of interleukin-6 and mammalian keratinocyte-derived chemokine. PSC cytokine production was not affected by acute hyperglycemia. Syngeneic islets co-cultured with PSCs for 24-48 h increased their insulin release and lowered their insulin content. However, short-term insulin release in batch-type incubations was unaffected after 48 h of co-culture. Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days.

Conclusion: Activated PSCs may contribute to impaired islet endocrine function seen in exocrine pancreatitis and in islet fibrosis associated with some cases of type 2 diabetes.

No MeSH data available.


Related in: MedlinePlus