What is it about?
SGLT2 inhibitors increase plasma glucagon levels in type 2 diabetes. We previously demonstrated that SGLT2 protein was specifically expressed in human alpha cells, where its inhibition directly promotes glucagon secretion. These findings were later reported to be difficult to reproduce. We hypothesized that inter-individual heterogeneity in SGLT2 expression and regulation may impact on glucagon secretion by human alpha cells in response to SGLT2 inhibitors. The results revealed a high inter-donor variability of SGLT2 protein expression and corresponding variability in glucagon secretory responses contribute to inter-individual differences in response to SGLT2 inhibitors.
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Why is it important?
Human islet heterogeneity in SGLT2 expression and function is an important parameter to consider for study design and interpretation of results. Islets from some donors did not respond to low-glucose nor SGLT2 inhibition with respect to glucagon secretion, thus suggesting a functional impairment of these islets to glucose-sensing and SGLT2 inhibition.
Perspectives
These findings may have clinical relevance since they may partially explain the heterogeneous plasma glucagon levels found in patients and their variable response to pharmacological treatment with SGLT2 inhibitors.
Caroline Bonner
Institut Pasteur de Lille
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This page is a summary of: Interindividual Heterogeneity of SGLT2 Expression and Function in Human Pancreatic Islets, Diabetes, January 2020, American Diabetes Association,
DOI: 10.2337/db19-0888.
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