Ectopic Expression of GIP in Pancreatic β-Cells Maintains Enhanced Insulin Secretion in Mice With Complete Absence of Proglucagon-Derived Peptides
| Autor: | Daniel J. Drucker, Yoshiko Takagishi, Michiyo Yamamoto, Eriko Sakamoto-Miura, Shin Tsunekawa, Ayako Fukami, Yusuke Seino, Yutaka Seino, Yoshiharu Murata, Chisato Sugiyama, Yoshitaka Hayashi, Nobuaki Ozaki, Safina Ali, Tatsuhito Himeno, Yutaka Oiso |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty endocrine system Endocrinology Diabetes and Metabolism medicine.medical_treatment 030209 endocrinology & metabolism Enteroendocrine cell Gastric Inhibitory Polypeptide Biology Proglucagon Glucagon Incretins Glucagon-Like Peptide-1 Receptor Green fluorescent protein Receptors Gastrointestinal Hormone 03 medical and health sciences Mice 0302 clinical medicine Gastric inhibitory polypeptide Internal medicine Insulin-Secreting Cells Glucose Intolerance Insulin Secretion Internal Medicine medicine Cyclic AMP Receptors Glucagon Glucose homeostasis Animals Homeostasis Insulin Gene Knock-In Techniques 030304 developmental biology Original Research 0303 health sciences Glucose tolerance test medicine.diagnostic_test fungi Glucose Tolerance Test Immunohistochemistry Peptide Fragments 3. Good health Endocrinology Islet Studies hormones hormone substitutes and hormone antagonists Gene Deletion |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Glucagon and glucagon-like peptide-1 (GLP-1) are produced in pancreatic a-cells and enteroendocrine L-cells, respectively, in a tissue-specific manner from the same precursor, proglucagon, that is encoded by glucagon gene (Gcg), and play critical roles in glucose homeostasis. Here, we studied glucose homeostasis and b-cell function of Gcg-deficient mice that are homozygous for a Gcg-GFP knock-in allele (Gcg gfp/gfp ). The Gcg gfp/gfp mice displayed improved glucose tolerance and enhanced insulin secretion, as assessed by both oral glucose tolerance test (OGTT) and intraperitoneal glucose tolerance test (IPGTT). Responses of glucose-dependent insulinotropic polypeptide (GIP) to both oral and intraperitoneal glucose loads were unexpectedly enhanced in Gcg gfp/gfp mice, and immunohistochemistry localized GIP to pancreatic b-cells of Gcg gfp/gfp mice. Furthermore, secretion of GIP in response to glucose was detected in isolated islets of Gcg gfp/gfp mice. Blockade of GIP action in vitro and in vivo by cAMP antagonism and genetic deletion of the GIP receptor, respectively, almost completely abrogated enhanced insulin secretion in Gcg gfp/gfp mice. These results indicate that ectopic GIP expression in b-cells maintains insulin secretion in the absence of proglucagon-derived peptides (PGDPs), revealing a novel compensatory mechanism for sustaining incretin hormone action in islets. Diabetes 62:510–518, 2013 |
| Databáze: | OpenAIRE |
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