A Study On The Relationship Of Gallbladder Contractility And Gallstone Formation In Diabetic Guinea Pigs

Objective To study the relationship between the formation of gallbladder stones and diabetes mellitus and to investigate the effects of diabetes mellitus on motility of gallbladder in streptozotocin-treated guinea pigs.Methods Diabetes mellitus was induced in guinea pigs with a single intraperitoneal injection of streptozotocin. After successful being induced of diabetes mellitus, the guinea pigs were divided into four groups fed a normal chow or a lithogenic diet (LD) consisted of 1% cholesterol and 0.5% cholic acid. The groups constituted as follows: 12 normal guinea pigs on a normal chow (control group), 12 normal guinea pigs on LD (LD group), 12 diabetes mellitus guinea pigs on a normal chow (DM group), and 13 diabetes mellitus guinea pigs on LD (DM + LD group). At the end of the 4 weeks or 8 weeks the animals were killed and the volumes of gallbladder were detected. The gallbladder bile was carefully inspected for microscopic cholesterol crystals and gallstones. Gallbladder muscle strip contractile responses to ACh, CCK and KCl in vitro were constructed alone.Results The incidence of gallstones in control group, LD group, DM group and DM+LD group were 0%, 83.3%, 25.0% and 92.3%, and the occurrence of crystals were 0%, 100%, 66.7% and 100%, respectively. The volumes of gallbladder in LD, DM and DM+LD were remarkably bigger than control group at the end of the 4 weeks and at the end of the 8 weeks (P<0.01). Compared with control group, the contractile responses of LD and DM+LD gallbladder muscle strip in vitro to ACh and CCK was significantly decreased (P<0.01). The contractile responses of gallbladder strip from LD, DM+LD and control group in vitro to KCl were no significant differences at the end of 4 weeks (P>0.05), the LD and DM+LD gallbladder strip responses to KCl, however, reduced markedly compared with control group at the end of the 8 weeks(P<0.05). The contractile responses of gallbladder strip from MD and control group in vitro to ACh, CCK and KCl were no significant differences at the end of 4 weeks (P>0.05). But at the end of 8 weeks, the DM gallbladder strip's responses to ACh and CCK decreased significantly compared with control group (P<0.01). At the end of the 4 weeks, the gallbladder volume of guinea pig was inversely correlated with the maximal contractile response of gallbladder muscle strip in vitro to ACh (r=-0.58, P=0.024). The volume of gallbladder was inversely correlated with the maximal contractile response of gallbladder muscle strip to CCK (r=-0.59, P=0.019). At the end of the 8 weeks, The volume of gallbladder was inversely correlated with the maximal contractile response of gallbladder muscle strip to Ach (r=-0.61, P=0.013). The volume of gallbladder was inversely correlated with the maximal contractile response of gallbladder muscle strip to CCK (r=-0.67, P=0.005).Conclusions Due to impaired gallbladder motility in diabetes mellitus the cholesterol in gallbladder bile was apt to educe and to form cholesterol crystal. The decrease in the magnitude of the contractile responses to neurotransmitter and gut hormone with no change in the sensitivity to them in diabetes mellitus can led to the gallbladder hypomotility. Attenuated contractile responses of gallbladder to neurotransmitter and gut hormone may be caused by a lower concentration of specific receptors on the gallbladder smooth muscle and impaired postreceptor intracellular signal transduction in smooth muscle.