Human Nutrition
KEYWORDS
HCO3- transport in pancreas
HEAD
CONTACT
| iga-ryu◎t.mail.nagoya-u.ac.jp (Please send a message after replacing "◎" mark with "@" mark. ) |
OUTLINE
Laboratory of Human Nutrition studies the physiology of digestion and absorption of nutrients. The main theme is “mechanisms of pancreatic bicarbonate secretion”. Cystic fibrosis and chronic pancreatitis involve indigestion and malnutrition due to impaired bicarbonate secretion by pancreatic ductal epithelium. Our laboratory is trying to clarify molecular pathogenesis of the diseases by mutli-faceted approach.
RESEARCH PROJECTS
1. Mechanisms for pancreatic bicarbonate secretion
Moisturization and alkalinization of mucosal epithelia are fundamental to mucosal defense and nutrients absorption. We are trying to clarify mechanisms for epithelial HCO3- secretion by using isolated pancreatic duct segments (diameter: ~100 μm). Pancreatic ductal epithelium produces alkaline fluid containing as much as 140 mM HCO3- in response to secretin stimulation. The lumen of isolated pancreatic duct is microperfused with artificial pancreatic juice. HCO3- transport is examined by monitoring changes in pH, volume, and membrane potential in intra- and extra-cellular microenvironment. We have constructed a computational model of pancreatic HCO3- secretion based on experimental data accumulated in our laboratory. Various ion channels/transporters are localized to basolateral or apical membranes, which accomplish vectorial HCO3- transport. The key molecule is the CFTR anion channel in the apical membrane.
2. Pathophysiology of cystic fibrosis and its related diseases
Cystic fibrosis is an autosomal recessive genetic disease caused by pathogenic variants of the CFTR gene. Dysfunction of CFTR channel impairs anion and water transport in bronchial and intestinal mucosa, pancreatic duct, bile duct, sweat duct, and vas deferens, which results in thick mucus/luminal fluid, then obstruction of the lumen and recurrent mucosal infection. Cystic fibrosis is the most common genetic disease in Europeans but is very rare in Asian population. Our laboratory is responsible for functional and genetic analysis, and patient registry of cystic fibrosis. Recent studies suggest that mild dysfunction of CFTR is a risk of chronic pancreatitis, male infertility, and diffuse panbronchiolitis.
BIBLIOGRAPHY
2025
- Tppp3 determines basal body positioning and identity of respiratory cilia via microtubule assembly and sphingolipid homeostasis. Sakai T, Kawakita M, Seki A, Takaoka K, Kurata M, Torikai J, Atsumi S, Yawata K, Noi K, Fukutani Y, Noguchi K, Kiyokawa H, Morimoto M, Takeuchi E, Minegishi K, Aoki Y, Fujimura S, Nishizaka T, Inoue T, Nagaoka K, Tsugawa H, Hayashi H, Ishiguro H, Kozono T, Ohsawa I, Fujita Y, Matsunami H, Hamada H, Shinohara K. Proc Natl Acad Sci USA 122: e2503931122, 2025.
2023
- Clinical and genetic features of cystic fibrosis in Japan. Kozawa Y, Yamamoto A, Nakakuki M, Fujiki K, Kondo S, Okada T, Fukuyasu T, Yamaguchi M, Taniguchi I, Nomura N, Liu L, Higuchi M, Niwa E, Sohma Y, Naruse S, Takeyama Y, Ishiguro H. J Hum Genet 68 (10): 671-680, 2023.
2022
- Bicarbonate transport of airway surface epithelia in luminally perfused mice bronchioles. Liu L, Yamamoto A, Yamaguchi M, Taniguchi I, Nomura N, Nakakuki M, Kozawa Y, Fukuyasu T, Higuchi M, Niwa E, Tamada T, Ishiguro H. J Physiol Sci 72 (1): 4, 2022.
2020
- Pancreatic Bicarbonate Secretion. Ishiguro H, Yamamoto A, Steward MC. In: Kuipers EJ (ed.) Encyclopedia of Gastroenterology 2nd Edition Vol. 4, pp. 24-29. 2020.
2017
- Bicarbonate-rich fluid secretion predicted by a computational model of guinea-pig pancreatic duct epithelium. Yamaguchi M, Steward MC, Smallbone K, Sohma Y, Yamamoto A, Ko SB, Kondo T, Ishiguro H. J Physiol 595: 1947-1972, 2017.
2011
- Microperfusion and micropuncture analysis of ductal secretion. Ishiguro H, Steward MC, Yamamoto A. In: Pancreapedia -Exocrine Pancreas Knowledge Base- 2011. American Pancreatic Association.
2005
- Mechanisms of bicarbonate secretion in the pancreatic duct. Steward MC, Ishiguro H, Case RM. Annu Rev Physiol 67:377-409, 2005.
MESSAGE
Hiroshi Ishiguro and Akiko Yamamoto are faculty members of Research Center of Health, Physical Fitness, and Sports (Higashiyama campus). The laboratory of Human Nutrition is located at the 2nd floor of the Building for Medical Research (Tsurumai campus). We welcome students who are interested in the gastrointestinal and nutritional physiology.
