Metabolic and Mitochondrial Disturbances in Streptozotocin-Treated Sprague-Dawley and Sherman Rats

Abstract

This study provides explanation for conflicting evidence in the literature relating to changes in mitochondrial function and metabolic parameters during chemically induced diabetes. Diabetes of 3 days' duration (early ketosis) did not alter heart, kidney, or liver mitochondrial respiratory rates with glutamate or succinate even though serum glucose and triglycerides were elevated. Diabetes of 5 weeks' duration did not alter kidney or liver mitochondrial function in thefed adult rat although weight gain was depressed. The amount of kidney mitochondrial protein isolated per gram of tissue was increased by 30% in the diabetic. This increase was reversed by insulin treatment as were the other biochemical modalities measured. Superimposition of a 24hr fast resulted in enhanced gluconeogenesis as measured by an animal weight loss of 17% within 24 hr (liver weight loss, 21%) and an elevation of serum urea nitrogen by 180% compared to fasted control. Respiratory rates of diabetic kidney mitochondria with glutamate were unaffected in the fasted animal whereas diabetic liver mitochondrial respiratory rates during succinate oxidation were reduced by 43%. Respiratory control was unchanged in the fasted diabetic rat. All the observed changes were reversed by insulin. Variation in the serum and liver metabolic indices (urea nitrogen, creatinine, glycerol, free fatty acids, free amino acids, triglycerides, and glucose) and liver mitochondrial responses to 7 weeks of chemically induced diabetes was affected by the rat strain, Sprague-Dawley versus Sherman, and rat weight, 72 g versus 222 g. Liver mitochondrial respirations in fed Sherman rats were not depressed by diabetes, Both rat strains had elevated liver free fatty acids and glutamate dehydrogenase activity in the diabetic state. Serum leucine, isoleucine, and valine were more elevated and serum lysine and arginine were more depressed in the diabetic Sprague-Dawley rat than in the Sherman rat. Conjectures on these results are presented in the text. 0

Cardiac mitochondrial damage and biogenesis in a chronic model of type 1 diabetes

“…All of these measures were elevated in mitochondria of 5-mo-old OVE26 heart by 18 -50%, strongly indicating that mitochondrial biogenesis had occurred. Diabetes has been shown to increase mitochondrial protein yield from kidney and heart (40,43). Dysfunctional mitochondria bring about synthesis of mitochondrial components in patients with inherited mitochondrial defects (22) and in cultured cells (18,30) with impaired mitochondria.…”

Higher efficiency of the liver phosphorylative system in diabetic Goto‐Kakizaki (GK) rats

“…A review of the literature of experimental diabetes produced by treatment with streptozotocin or alloxan claims attention for defects in mitochondrial function [16–18]. However, at present, little is known about the mechanisms or the progression of these defects.…”

Effect of streptozotocin-induced diabetes on oxidative energy metabolism in rat liver mitochondria—A comparative study of early and late effects

“…The basic defects in diabetes mellitus are impaired glucose metabolism and basement membrane alterations (1)(2)(3). Besides, mitochondrial oxidative energy metabolism also seems to be impaired in experimental diabetes (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). With respect to the mitochondrial respiratory activity one regulatory factor which is affected in diabetes is the pyruvate Mackerer et aL (8) reported increased respiration rates with normal P/O ratios.…”

“…The apparent contradiction could possibly be attributed to several factors e.g. the nature of the diabetogen used, the dose employed, the route of administration and the time at which the effects were examined (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Additionally, the responses could also vary depending on the strain of the animals used (13)(14)(15)(16).…”

“…It is anticipated that examination of the diabetesassociated defects and efficacy of insulin treatment at early and late stages of the disease can help in getting better insights in the management of the maladies of the disease (1)(2)(3). Additionally, the problem of contradictory reports in the literature can also be addressed to (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Results of these experiments are described hera.…”