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Mixed Primary Cultures of Murine Small Intestine Intended for the Study of Gut Hormone Secretion and Live Cell Imaging of Enteroendocrine Cells
Published on: April 20, 2017
Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut
Yukihiro Fujita1, Ali Asadi, Gary K Yang
1Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, Canada.
American Journal of Physiology. Gastrointestinal and Liver Physiology
|February 27, 2010
Summary
Researchers discovered a new, shorter form of the hormone glucose-dependent insulinotropic polypeptide (GIP), called GIP(1-30). This biologically active GIP isoform is produced in gut K cells and plays a role in digestion.
Area of Science:
- Endocrinology
- Gastroenterology
- Molecular Biology
Background:
- Glucose-dependent insulinotropic polypeptide (GIP) is a key incretin hormone secreted by enteroendocrine K cells postprandially.
- The canonical GIP form, GIP(1-42), is processed from its precursor pro-GIP by proprotein convertase subtilisin/kexin type 1 (PC1/3).
Purpose of the Study:
- To investigate the potential generation and biological activity of a truncated GIP isoform, GIP(1-30).
- To identify the processing enzymes and cellular localization of this novel GIP form.
Main Methods:
- Immunohistochemistry using region-specific GIP antibodies in mouse and human tissues.
- Analysis of GIP processing in wild-type and PC2-deficient mice.
- In vitro studies on somatostatin release in perfused mouse stomach.
Main Results:
- A subset of K cells exhibited GIP immunoreactivity with mid-region antibodies but not COOH-terminal antibodies, suggesting a truncated form.
- This truncated GIP form, GIP(1-30), was found to be processed by PC2 in a subset of K cells.
- GIP(1-30) demonstrated comparable potency to GIP(1-42) in stimulating somatostatin release.
Conclusions:
- GIP(1-30) is a naturally occurring, biologically active GIP isoform produced in the gut.
- The proprotein convertase PC2 is involved in the generation of GIP(1-30).
- This finding expands our understanding of GIP processing and its physiological roles.
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