The incidence of gallstone is higher in patients with diabetes mellitus than in general popula- tion. It is generally attributed to hypomotility and lowered emptying function of the gallblad- der. In this study, we investigate if chronic hy- perglycemia is correlated with reduced contrac- tile function of the bile ducts in rat. Hypergly- cemic rats were induced by streptozotocin-nic-otinamide treatment. Hyperglycemic rats were sacrificed eight months after induction and bile ducts were removed for the subsequent studies. The bile duct contractility of the normal rats is consistently higher than that of the hypergly- cemic rats. The contractities were measured to be 5.5 ± 0.2 mg vs. 4.2 ± 0.1 mg without CCK stimulation, and 5.5 ± 0.3 mg vs. 7.9 ± 0.4 mg with CCK stimulation, respectively for hypergly-cemic and normal rats. There was no significant difference in plasma CCK concentration in hy- perglycemic rats and normal rats. The expres- sion of CCK-A receptor protein in the bile duct tissue was decreased in hyperglycemic rats compared with that of the normal rats, and it may, at least in part, responsible for a reduced contractility. A reduced bile duct motility may cause bile retention, and may be one of the factors predispose to gallstone formation in type 2 diabetes patients, which is characterized with chronic hyperglycemia.
Wittenburg, H., Lyons, M.A., Li, R., Churchill, G.A., Carey, M.C. and Paigen, B.J. (2003) FXR and ABCG5/ ABCG8 as determinants of cholesterol gallstone forma- tion from quantitative trait locus mapping in mice. Gas- troenterology, 125(3), 868-881.
Pagliarulo, M., Fornari, F., Fraquelli, M., Zoli, F., Giangregorio, A., Grigolon, M., Peracchi, D. and Conte, D. (2004) Gallstone disease and related risk factors in a large cohort of diabetic patients. Digestive and Liver Disease, 36(2), 130-134.
Portincasa, P., Moschetta, A., Berardino, M., Di-Ciaula, A., Vacca, M., Baldassarre, G., Pietrapertosa, A., Camma- rota, R., Tannoia, N. and Palasciano, G. (2004) Impaired gallbladder motility and delayed orocecal transit con- tribute to pigment gallstone and biliary sludge formation in betathalassemia major adults. World Journal of Gas- troenterology, 10(16), 2383-2390.
Masiello, P., Broca, C., Gross, R., Roye, M., Manteghetti, M., Hillaire-Buys, D., Novelli, M. and Ribes, G. (1998) Experimental NIDDM: Development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes, 47(2), 224-229.
Mendez-Sanchez, N., Vega, H., Uribe, M., Guevara, L., Ramos, M.H. and Vargas-Vorackova, F. (1998) Risk fac- tors for gallstone disease in Mexicans are similar to those found in Mexican-Americans. Digestive and Liver Dis- ease, 43(5), 935-939.
Férézou, J., Combettes-Souverain, M., Souidi, M., Smith, J.L., Boehler, N., Milliat, F., Eckhardt, E., Blanchard, G., Riottot, M., Sérougne, C. and Lutton, C. (2000) Choles- terol, bile acid, and lipoprotein metabolism in two strains of hamster, one resistant, the other sensitive (LPN) to su- crose-induced cholelithiasis. Journal of Lipid Research, 41(12), 2042-2052.
Xiong, D., Chang-You, L., Ying, M., Chang-An, L. and Yu-Jun, S. (2005) Correlation between gene expression of CCK-A receptor and emptying dysfunction of the gall- bladder in patients with gallstones and diabetes mellitus. Hepatobiliary & Pancreatic Diseases International, 4(2), 295-298.
Miyasaka, K., Kanai, S., Ohta, M., Hosoya, H., Sekime, A., Akimoto, S., Takiguchi, S. and Funakoshi, A. (2007) Ageassociated gallstone formation in male and female CCK-1(A) receptor-deficient mice. Journal of Gastroen- terology, 42(6), 493-496.