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Published on: September 1, 2015
Structure and function of the pancreas in the polycystic kidney rat
Lanjuan Yi1, Satoru Naruse, Sonoko Furuya
1Department of Human Nutrition, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Insights
Polycystic kidney (PCK) rats, models for human autosomal recessive polycystic kidney disease, show altered pancreatic duct structure and reduced fluid secretion. These findings suggest primary cilia influence pancreatic duct function.
Area of Science:
- Cell Biology
- Genetics
- Physiology
Background:
- Autosomal recessive polycystic kidney disease (ARPKD) is linked to mutations in the Pkhd1 gene, which encodes fibrocystin, a ciliary protein.
- PCK rats, a model for ARPKD, develop kidney and liver cysts due to Pkhd1 mutations.
- The role of primary cilia in pancreatic duct structure and function remains unclear.
Purpose of the Study:
- To investigate the structure and function of the exocrine pancreas in PCK rats.
- To determine the role of fibrocystin and primary cilia in pancreatic duct regulation.
Main Methods:
- Collected pancreatic juice and bile from anesthetized PCK and wild-type (WT) rats.
- Analyzed pancreatic ductal structure using microdissection and immunohistochemistry.
- Assessed pancreatic duct distensibility and fluid secretion in response to secretin and carbamylcholine.
Main Results:
- Pancreatic acini appeared normal; no pancreatic cysts were observed.
- Larger pancreatic ducts in PCK rats showed irregular dilation and increased AQP1 expression.
- PCK rat pancreatic ducts exhibited significantly higher distensibility than WT rats.
- Fluid secretion in response to low-dose secretin was reduced in PCK rats, but not at higher doses.
- Amylase secretion was comparable between PCK and WT rats.
Conclusions:
- Fibrocystin and primary cilia may regulate pancreatic ductal structure.
- These mechanisms appear to play a role in controlling pancreatic fluid secretion.
Objectives:
Mutation in the Pkhd1 gene that encodes a ciliary protein, fibrocystin, causes multiple cysts in the kidneys and liver in the polycystic kidney (PCK) rat, a model for human autosomal recessive PCK disease. To clarify the role of primary cilia in the pancreatic duct, we examined the structure and function of the exocrine pancreas of PCK rats.
Methods:
Pancreatic juice and bile were collected from anesthetized rats. Pancreatic ductal structure was analyzed by microdissection and immunohist0chemistry.
Results:
Histologically pancreatic acini were apparently normal, and no cysts were detected in the pancreas. Larger pancreatic ducts were irregularly dilated with enhanced expression of AQP1 in epithelial cells. The pancreatic duct of PCK rats exhibited significantly (P < 0.05) higher distensibility than that of wild-type (WT) rat at a physiological luminal pressure (3 cm H2O). Pancreatic fluid secretion stimulated with a physiological dose of secretin (0.03 nmol/kg per hour) in PCK rats was significantly smaller than that in WT, but the differences were not significant at higher doses. The amylase responses to carbamylcholine were not different between PCK and WT rats.
Conclusions:
These findings suggest that fibrocystin/primary cilia-dependent mechanisms may play a role in the regulation of pancreatic ductal structure and fluid secretion.
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