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Extra-pancreatic expression of the rat islet amyloid polypeptide (amylin) gene
C G Nicholl1, J M Bhatavdekar, J Mak
1Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.
Abstract:
Messenger RNA for rat islet amyloid polypeptide (IAPP) has been identified not only in the pancreas but also, in lesser amounts, in preparations from the stomach and dorsal root ganglia. In the stomach, insulin mRNA was not detectable, ruling out possible contamination by pancreatic tissue. Because IAPP and calcitonin gene-related peptide (CGRP) are related and CGRP is present in both stomach and dorsal root ganglia, it was possible that 'IAPP' signals were in fact due to cross-hybridization with CGRP mRNA. A second IAPP probe was constructed which does not cross-react. This probe also detected mRNA in both tissues, confirming the expression of IAPP in both tissues. The regional distribution of IAPP mRNA in the stomach did not parallel that of gastrin mRNA. IAPP mRNA was present in the antrum, centrum and pylorus and, like gastrin, the highest amounts were in the pylorus. However, the ratio between the pylorus and centrum was 3.6:1 for IAPP and 156:1 for gastrin. The effects of dietary manipulation were determined; a period of 48 h of starvation reduced pancreatic IAPP mRNA by approximately 60%, whereas in the stomach there was no significant reduction. If the action of IAPP was hormonal, pancreas and stomach would not be acting in concert. A paracrine role for gastric IAPP therefore seems more likely.
Insights
Rat islet amyloid polypeptide (IAPP) mRNA is found in the stomach, not just the pancreas. Gastric IAPP may have a local paracrine function rather than a systemic hormonal role.
Area of Science:
- Endocrinology
- Molecular Biology
- Gastroenterology
Background:
- Islet amyloid polypeptide (IAPP) mRNA is primarily known in pancreatic islets.
- Calcitonin gene-related peptide (CGRP) shares similarities with IAPP and is found in the stomach and dorsal root ganglia.
- Previous studies suggested potential IAPP expression outside the pancreas, but cross-reactivity with CGRP mRNA was a concern.
Purpose of the Study:
- To confirm and characterize the expression of islet amyloid polypeptide (IAPP) mRNA in rat stomach and dorsal root ganglia.
- To investigate the distribution and regulation of gastric IAPP mRNA.
- To explore the potential physiological role of gastric IAPP.
Main Methods:
- Northern blot analysis using specific IAPP probes to detect mRNA.
- Construction of a second, non-cross-reactive IAPP probe to validate findings.
- Analysis of IAPP mRNA distribution within different regions of the stomach.
- Assessment of IAPP mRNA levels following a 48-hour starvation period.
Main Results:
- IAPP mRNA was detected in rat stomach and dorsal root ganglia, distinct from insulin mRNA.
- A newly designed IAPP probe confirmed expression in these tissues, ruling out CGRP cross-hybridization.
- Gastric IAPP mRNA distribution varied regionally, with higher concentrations in the pylorus compared to the centrum.
- Pancreatic IAPP mRNA decreased significantly after starvation, while gastric IAPP mRNA remained largely unaffected.
Conclusions:
- Rat islet amyloid polypeptide (IAPP) is expressed in the stomach and dorsal root ganglia.
- Gastric IAPP mRNA expression is regulated differently from pancreatic IAPP mRNA, particularly under starvation conditions.
- The distinct regulation and distribution suggest a paracrine rather than a hormonal role for IAPP in the stomach.