Diabetes-induced cholestasis in the rat: possible role of hyperglycemia and hypoinsulinemia.

Abstract

In one of our earlier studies, an impaired biliary function in diabetes was suggested. We studied bile formation in rats with streptozotocin-induced diabetes (60 mg per kg body weight). Diabetic rats showed hyperglycemia and hypoinsulinemia, but no significant changes in hematocrit, plasma protein concentration or plasma osmolality. Bile flow was significantly (p less than 0.05) reduced (-23%) as compared with control animals, despite a higher (p less than 0.05) bile acid secretion rate (+56%). The biliary responses to three choleretic compounds (taurocholate, ursodeoxycholate and insulin), acting in a very different way upon bile formation, were not impaired in diabetes. The study of the relationship between bile acid output and bile flow, after infusion of taurocholate at different doses (0.25 to 1.5 mumoles per min per 100 gm body weight) showed that diabetes-induced cholestasis in the rat is mainly related to a decreased bile acid-independent fraction of the bile flow. We tested the possible role of hyperglycemia and hypoinsulinemia as cholestatic factors in diabetes. Glucose infusion [300 mM, 150 microliter per min (Group G)] induced a significant (p less than 0.05) reduction in bile flow (-0.33 microliter per min per gm liver) as compared to the basal period. After acute pancreatectomy (P) or mannoheptulose treatment [0.14 mmole per 100 gm body weight (Group M)], similar cholestatic effects were observed (-0.29 and -0.27 microliter per min per gm liver, respectively). However, plasma glucose and insulin concentrations were higher (p less than 0.01) in Group G than in P or M.(ABSTRACT TRUNCATED AT 250 WORDS)