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Defective prohormone processing and altered pancreatic islet morphology in mice lacking active SPC2
1Department of Biochemistry and Molecular Biology, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
Summary
Mice lacking prohormone convertase SPC2 (PC2) exhibit impaired prohormone processing, leading to fasting hypoglycemia and altered pancreatic islet cell populations. These SPC2-defective mice are valuable for studying neuroendocrine precursor mechanisms.
Area of Science:
- Endocrinology
- Molecular Biology
- Neuroscience
Background:
- Prohormone convertase SPC2 (PC2) is crucial for processing neuroendocrine precursors like proinsulin and proglucagon.
- SPC2 functions with SPC3 (PC3/PC1) in the regulated secretory pathway.
Purpose of the Study:
- To investigate the physiological consequences of lacking active SPC2 by creating a knockout mouse model.
- To elucidate the role of SPC2 in neuroendocrine precursor processing and hormone regulation.
Main Methods:
- Generation of SPC2-deficient mice by inserting a neomycin resistance gene into the mSPC2 gene.
- Analysis of homozygous mutant mice for growth, blood glucose levels, and pancreatic islet morphology.
Main Results:
- Homozygous mutant mice showed reduced growth, chronic fasting hypoglycemia, and impaired glucose tolerance.
- Defective processing of proglucagon, prosomatostatin, and proinsulin was observed in pancreatic islets.
- Pancreatic islets displayed alpha and delta cell hyperplasia and beta cell diminution.
Conclusions:
- SPC2 is essential for normal prohormone processing and glucose homeostasis.
- SPC2 deficiency leads to significant alterations in pancreatic islet composition and function.
- SPC2-defective mice provide a valuable model for studying neuroendocrine precursor processing and peptide hormone physiology.