Polyamine and amino acid content, and activity of polyamine-synthesizing decarboxylases, in liver of streptozotocin-induced diabetic and insulin-treated diabetic rats

Abstract

1. Concentrations of polyamines, amino acids, glycogen, nucleic acids and protein, and activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, were measured in livers from control, streptozotocin-diabetic and insulin-treated diabetic rats. 2. Total DNA per liver and protein per mg of DNA were unaffected by diabetes, whereas RNA per mg of DNA and glycogen per g of liver were decreased. Insulin treatment of diabetic rats induced both hypertrophy and hyperplasia, as indicated by an increase in all four of these constituents to or above control values. 3. Spermidine content was increased in the livers of diabetic rats, despite the decrease in RNA, but it was further increased by insulin treatment. Spermine content was decreased by diabetes, but was unchanged by insulin treatment. Thus the ratio spermidine/spermine in the adult diabetic rat was more typical of that seen in younger rats, whereas insulin treatment resulted in a ratio similar to that seen in rapidly growing tissues. 4. Ornithine decarboxylase activity was variable in the diabetic rat, showing a positive correlation with endogenous ornithine concentrations. This correlation was not seen in control or insulin-treated rats. Insulin caused a significant increase in ornithine decarboxylase activity relative to control or diabetic rats. 5. S-Adenosylmethionine decarboxylase activity was increased approx. 2-fold by diabetes and was not further affected by insulin. 6. Hepatic concentrations of the glucogenic amino acids, alanine, glutamine and glycine were decreased by diabetes. Their concentrations and that of glutamate were increased by injection of insulin. Concentrations of ornithine, proline, leucine, isoleucine and valine were increased in livers of diabetic rats and were decreased by insulin. Diabetes caused a decrease in hepatic concentration of serine, threonine, lysine and histidine. Insulin had no effect on serine, lysine and histidine, but caused a further fall in the concentration of threonine.

Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes

“…In skeletal muscle and in the liver, the BCAAs were higher at both ages, although the difference was not always statistically significant. The increase in BCAAs in this model of type 2 diabetes is consistent with reports of type 1 diabetes by Bloxam (1972) and Brosnan et al (1980Brosnan et al ( , 1983 in streptozotocin-diabetic rats. Isoleucine, leucine, and valine are essential amino acids.…”

“…In our model of type 2 diabetes, glutamine was lower in plasma, liver, and skeletal muscle; alanine concentrations were comparable to the controls in plasma and liver, but levels in the muscle were higher at both 5 and 11 weeks. In streptozotocindiabetic rats, Williamson et al (1967) and Brosnan et al (1980) found decreased levels of both alanine and glutamine in plasma. Hundal et al (1992) found a reduction in intrasarcolemmal glutamine levels in streptozotocin-diabetic rats.…”

“…These findings were confirmed in our laboratory. Brosnan et al (1980Brosnan et al ( , 1983 also observed a reduction in gluconeogenic amino acids in the plasma and liver of streptozotocin-diabetic rats. They found a decreased concentration of histidine and increased levels of proline, valine, isoleucine, and leucine in muscles.…”

Metabonomic analysis of the therapeutic effect of Zhibai Dihuang Pill in treatment of streptozotocin-induced diabetic nephropathy

“…This result is consistent with previous observations (Brosnan et al, 1980;Zulak et al, 2008). As important insulin secretatogues, BCAAs exert a regulatory influence on proteolysis and thus play important roles in building body organs (Brosnan et al, 1983).…”

1H NMR-based Metabonomic Analysis of Metabolic Changes in Streptozotocin-induced Diabetic Rats

“…It has been reported that insulin induced hypertrophy and hyperplasia in livers of diabetic rats 26 and caused a concomitant increase in the activity of some enzymes. 27 Probably for this reason the trend of the INS-STZ group in the score plot of liver tissue extract is not consistent with those of the urine and serum samples described above.…”