20 min listen
Diseased human pancreas and liver microphysiological system for preclinical diabetes research
Diseased human pancreas and liver microphysiological system for preclinical diabetes research
ratings:
Length:
20 minutes
Released:
Jul 3, 2023
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.07.03.547412v1?rss=1
Authors: Rigal, S., Casas, B., Kanebratt, K. P., Wennberg Huldt, C., Magnusson, L. U., Mullers, E., Kalrsson, F., Clausen, M., Hansson, S. F., Jansson Lofmark, R., Ammala, C., Marx, U., Gennemark, P., Cedersund, G., Andersson, T. B., Vilen, L. K.
Abstract:
Current research on metabolic disorders such as type 2 diabetes relies on animal models because multi-organ diseases cannot be well studied with the standard in vitro assays. Here, we connect models of key metabolism organs, pancreas and liver, on a microfluidic chip to enable diabetes research in a human-based preclinical system. Aided by mechanistic mathematical modelling, we developed a two-organ microphysiological system (MPS) that replicates clinically-relevant phenotypes of diabetic dysregulation both in the liver and pancreas compartments. Exposure to hyperglycemia and high cortisone created a diseased pancreas-liver MPS which displayed beta-cell dysfunction, steatosis, elevated ketone-body secretion, increased glycogen storage, and upregulated gluconeogenic machinery. In turn, normoglycemia and physiological cortisone concentration maintained glucose tolerance and stable liver and beta-cell functions. This method was evaluated for repeatability in two laboratories and was effective in multiple pancreatic islet donors. The model also provides a platform to identify new therapeutic targets as demonstrated with a liver-secreted IL-1R2 protein that induced islet proliferation.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
http://biorxiv.org/cgi/content/short/2023.07.03.547412v1?rss=1
Authors: Rigal, S., Casas, B., Kanebratt, K. P., Wennberg Huldt, C., Magnusson, L. U., Mullers, E., Kalrsson, F., Clausen, M., Hansson, S. F., Jansson Lofmark, R., Ammala, C., Marx, U., Gennemark, P., Cedersund, G., Andersson, T. B., Vilen, L. K.
Abstract:
Current research on metabolic disorders such as type 2 diabetes relies on animal models because multi-organ diseases cannot be well studied with the standard in vitro assays. Here, we connect models of key metabolism organs, pancreas and liver, on a microfluidic chip to enable diabetes research in a human-based preclinical system. Aided by mechanistic mathematical modelling, we developed a two-organ microphysiological system (MPS) that replicates clinically-relevant phenotypes of diabetic dysregulation both in the liver and pancreas compartments. Exposure to hyperglycemia and high cortisone created a diseased pancreas-liver MPS which displayed beta-cell dysfunction, steatosis, elevated ketone-body secretion, increased glycogen storage, and upregulated gluconeogenic machinery. In turn, normoglycemia and physiological cortisone concentration maintained glucose tolerance and stable liver and beta-cell functions. This method was evaluated for repeatability in two laboratories and was effective in multiple pancreatic islet donors. The model also provides a platform to identify new therapeutic targets as demonstrated with a liver-secreted IL-1R2 protein that induced islet proliferation.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Jul 3, 2023
Format:
Podcast episode
Titles in the series (100)
A genome-wide CRISPR interference screen using an engineered trafficking biosensor reveals a role for RME-8 in opioid receptor regulation by PaperPlayer biorxiv cell biology