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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

Effects of mouse pancreatic stellate cells on beta-cell replication. A: β-TC6 cells cultured alone or co-cultured with isolated mouse pancreatic stellate cells for 24 h. B: Isolated mouse pancreatic islets cultured without or with isolated mouse pancreatic stellate cells for 72 h. At least 3,000 cells/experimental group were counted for each observation. Values are means ± SEM for 4–5 experiments.** P < 0.01, and *** P < 0.001 when compared with mono-cultures.
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Figure 4: Effects of mouse pancreatic stellate cells on beta-cell replication. A: β-TC6 cells cultured alone or co-cultured with isolated mouse pancreatic stellate cells for 24 h. B: Isolated mouse pancreatic islets cultured without or with isolated mouse pancreatic stellate cells for 72 h. At least 3,000 cells/experimental group were counted for each observation. Values are means ± SEM for 4–5 experiments.** P < 0.01, and *** P < 0.001 when compared with mono-cultures.

Mentions: β-TC6 cells were harvested during passage 3–8 and then cultured with or without attached PSCs in the culture dish. There was a clear and consistent reduction in EdU-staining in PDX-1-positive cells (Figure 4A), and this was also seen when mouse islets were similarly cultured together with PSCs (Figure 4B).


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)

Effects of mouse pancreatic stellate cells on beta-cell replication. A: β-TC6 cells cultured alone or co-cultured with isolated mouse pancreatic stellate cells for 24 h. B: Isolated mouse pancreatic islets cultured without or with isolated mouse pancreatic stellate cells for 72 h. At least 3,000 cells/experimental group were counted for each observation. Values are means ± SEM for 4–5 experiments.** P < 0.01, and *** P < 0.001 when compared with mono-cultures.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Effects of mouse pancreatic stellate cells on beta-cell replication. A: β-TC6 cells cultured alone or co-cultured with isolated mouse pancreatic stellate cells for 24 h. B: Isolated mouse pancreatic islets cultured without or with isolated mouse pancreatic stellate cells for 72 h. At least 3,000 cells/experimental group were counted for each observation. Values are means ± SEM for 4–5 experiments.** P < 0.01, and *** P < 0.001 when compared with mono-cultures.
Mentions: β-TC6 cells were harvested during passage 3–8 and then cultured with or without attached PSCs in the culture dish. There was a clear and consistent reduction in EdU-staining in PDX-1-positive cells (Figure 4A), and this was also seen when mouse islets were similarly cultured together with PSCs (Figure 4B).

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