Language
English
Publication Date
3-2-2021
Journal
Proceedings of the National Academy of Sciences of the United States of America
DOI
10.1073/pnas.2022142118
PMID
33619103
PMCID
PMC7936318
PubMedCentral® Posted Date
2-22-2021
PubMedCentral® Full Text Version
Post-print
Abstract
We evaluated the potential for a monoclonal antibody antagonist of the glucagon receptor (Ab-4) to maintain glucose homeostasis in type 1 diabetic rodents. We noted durable and sustained improvements in glycemia which persist long after treatment withdrawal. Ab-4 promoted β-cell survival and enhanced the recovery of insulin+ islet mass with concomitant increases in circulating insulin and C peptide. In PANIC-ATTAC mice, an inducible model of β-cell apoptosis which allows for robust assessment of β-cell regeneration following caspase-8–induced diabetes, Ab-4 drove a 6.7-fold increase in β-cell mass. Lineage tracing suggests that this restoration of functional insulin-producing cells was at least partially driven by α-cell-to-β-cell conversion. Following hyperglycemic onset in nonobese diabetic (NOD) mice, Ab-4 treatment promoted improvements in C-peptide levels and insulin+ islet mass was dramatically increased. Lastly, diabetic mice receiving human islet xenografts showed stable improvements in glycemic control and increased human insulin secretion.
Keywords
Animals, Antibodies, Monoclonal, Blood Glucose, C-Peptide, Cell Lineage, Cell Transdifferentiation, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Gene Expression, Glucagon, Glucagon-Secreting Cells, Humans, Hypoglycemic Agents, Insulin, Insulin-Secreting Cells, Islets of Langerhans, Islets of Langerhans Transplantation, Mice, Mice, Inbred NOD, Organ Size, Receptors, Glucagon, Treatment Outcome, insulin, glucagon, islet, regeneration, diabetes
Published Open-Access
yes
Recommended Citation
Wang, May-Yun; Dean, E Danielle; Quittner-Strom, Ezekiel; et al., "Glucagon Blockade Restores Functional β-Cell Mass in Type 1 Diabetic Mice and Enhances Function of Human Islets" (2021). Faculty and Staff Publications. 1036.
https://digitalcommons.library.tmc.edu/baylor_docs/1036
Included in
Animals Commons, Cardiology Commons, Cardiovascular Diseases Commons, Endocrinology, Diabetes, and Metabolism Commons, Medical Cell Biology Commons, Medical Genetics Commons