Liver regeneration in normal and alloxan‐induced diabetic rats

Abstract

The effects of alloxan-induced diabetes on liver regeneration were investigated. Normal and diabetic rats were sacrificed at eight time periods between 16 hours and 4 weeks following two-thirds partial hepatectomy or sham operation. The results indicate that alloxan-induced diabetes delays but does not prevent liver regeneration following partial hepatectomy. This delay is indicated by a depressed synthesis of RNA, DNA and protein during the first post-operative day and a lack of mitotic figures in the 24-hour sample. In addition, the synthesis of these three cellular constituents did not return to control levels as rapidly in the diabetics. Compared with the sham operated animals, the concentrations of total serum protein remained depressed longer in the diabetic hepatectomized animals. The data indicate that the metabolic alterations associated with alloxan diabetes delay the onset of the regenerative process and prolong the recovery period.

Using higher‐order crossings to distinguish liver regeneration indices in hepatectomized diabetic and non‐diabetic rats

“…Similarly, Figure 2b shows suppression and delay of TK activity during liver regeneration post‐PH in diabetic compared to control rats. These findings coincide with those found by Barra et al 8 . concerning the delay of the onset of the liver regeneration process due to the existence of experimentally induced diabetes mellitus, and with Starzl et al .’s, 37 data who first demonstrated the importance of insulin in liver regeneration, the absence of which (as in experimentally induced diabetes) impairs the regeneration process.…”

“…3b and 4b) is due to the small size of SET DNA and SET TK , which results in increased SD values. This could be easily eliminated, resulting in even more distant and more compact in character (smaller SD) clusters, by using even higher resolution within the SET DNA and SET TK , measuring the two liver regeneration indices at smaller time post‐PH intervals, such as 2 h or 1 h. However, even with the sampling post‐PH time intervals adopted in this study, which provide the highest resolution compared to other relevant studies, 6–12 the estimated dividing lines result in linear discrimination between the groups (zero false positives and false negatives).…”

“…Until now, only sporadic studies have been reported in the literature which, based on basic analytical methods, examine the regeneration capacity of the liver in diabetic animals and yet provide quite contradictory results 7–13 . In particular, in some published works, 12,13 a notable increase in the rate of the liver regeneration process in experimentally induced diabetic rats was found, whereas in others, a significant reduction in the rate of the liver regeneration process 11 or delay in its onset 8 was reported.…”

Liver regeneration following partial hepatectomy: genes and metabolism

“…Numerous studies through the years have pointed to insulin (Morley et al, 1975;Starzl and Terblanche, 1979;Starzl, 1980;Michalopoulos, 1990; Bucher and Strain, 1992), alt hough low levels may suffice, as suggested by the regenerative capacity of severely diabetic rats (Younger, King and Steiner, 1966; Barra and Hall, 1977).…”

Acceleration of Liver Regeneration by Malotilate in Partially Hepatectomized Rats

“…Indeed, malotilate tended to increase the mitotic index 1-3 days after partial hepatectomy in the rats (Table 1) as well as in the rats treated with alloxan (Table 2). The alloxan-diabetic rats seemed to be suffering from deficiency in insulin (10), which is one of the stimulating factors of liver regeneration (11)(12)(13). In the partially hepatectomized alloxan-diabetic rats, indeed, the mitotic index was as low as 0.53 instead of 2.27 as found in the untreated (partially hepatectomized) rats.…”