scholarly journals Effects of streptozotocin-diabetes and insulin administration in vivo or in vitro on the activities of five enzymes in the adipose-tissue triacylglycerol-synthesis pathway

1987 ◽  
Vol 243 (1) ◽  
pp. 289-292 ◽  
Author(s):  
E D Saggerson ◽  
C A Carpenter

At 2 days after administration of streptozotocin (100 mg/kg), activities in rat epididymal fat-pads of the following enzymes were significantly decreased: fatty acyl-CoA synthetase (FAS), mitochondrial and microsomal forms of glycerolphosphate acyltransferase (GPAT), monoacylglycerolphosphate acyltransferase (MGPAT) and Mg2+-dependent phosphatidate phosphohydrolase (PPH). There were no significant changes in diacylglycerol acyltransferase or Mg2+-independent PPH. Insulin administration to diabetic rats over 2 days restored activities of FAS, both forms of GPAT, MGPAT and Mg2+-dependent PPH. Significant restoration of all five activities was also seen 2 h after a single administration of insulin, but was not observed 45 min after insulin treatment. Insulin significantly increased all five enzyme activities when adipocytes from diabetic rats were incubated for 2 h with a mixture of glucose, lactate, pyruvate and amino acids.

1981 ◽  
Vol 241 (2) ◽  
pp. E129-E135 ◽  
Author(s):  
W. D. McCumbee ◽  
H. E. Lebovitz

Diabetes and malnutrition result in decreased somatomedin production and cartilage growth in rats. The growth and metabolism of the Swarm rat chondrosarcoma are dramatically affected by somatomedins. Data presented here show that streptozotocin diabetes and diet restriction inhibit in vivo chondrosarcoma growth. Tumors grown in diabetic rats were significantly smaller than tumors grown in diet-restricted rats showing the same changes in body weight. Insulin treatment increased the rate of tumor growth in diabetic rats. Tumors grown in rigidly controlled diabetic rats were as large as tumors grown in nondiabetic controls. Diet restriction and diabetes reduced the capacity of the serum of the rat to stimulate alpha-amino[14C]isobutyrate uptake and [3H]uridine incorporation into RNA in chondrosarcoma pieces grown in nondiabetic rats. This somatomedin activity of the serum was restored by treating diabetic rats with insulin. There was a significant correlation between the in vitro stimulatory effect of a particular serum pool on chondrosarcoma metabolism and in vivo chondrosarcoma growth in the animals from whom the serum was obtained. These studies demonstrate that the in vivo growth of malignant chondrocytes is similar to that of normal chondrocytes with respect to the role of nutrition and insulin.


1986 ◽  
Vol 239 (2) ◽  
pp. 275-284 ◽  
Author(s):  
S J Taylor ◽  
E D Saggerson

The subcellular distribution of Mg2+-dependent phosphatidate phosphohydrolase in rat adipocytes between a soluble and a membrane-bound fraction was measured by using both centrifugal fractionation and a novel Millipore-filtration method. The relative proportion of the phosphohydrolase associated with the particulate fraction was increased on incubation of cells with noradrenaline or palmitate. Insulin on its own decreased the proportion of the phosphohydrolase that was particulate and abolished the effect of noradrenaline, but not that of palmitate. The effect of noradrenaline on phosphohydrolase distribution was rapid, the effect being maximal within 10 min. Noradrenaline exerted this effect with a similar concentration-dependence to its lipolytic effect. Inclusion of albumin in homogenization buffers decreased the proportion of the phosphohydrolase that was particulate, but did not abolish the effect of noradrenaline. There was limited correlation between the proportion of the phosphohydrolase that was particulate and the measured rate of triacylglycerol synthesis in adipocytes incubated under a variety of conditions. Starvation, streptozotocin-diabetes and hypothyroidism decreased the specific activities of the phosphohydrolase and glycerolphosphate acyltransferase in homogenates from epididymal fat-pads. Restoration of these activities in the diabetic state was seen after administration of insulin over 2 days or, in the short term, within 2 h after a single administration of insulin. Administration of thyroxine over 3 days caused restoration of these activities in the hypothyroid state. Starvation and diabetes increased the proportion of the phosphohydrolase found in the microsomal fraction. This change was not seen when albumin was present in homogenization buffers. The possible role of fatty acids as regulators of the intracellular translocation of the phosphohydrolase, together with the role of this enzyme in the regulation of triacylglycerol synthesis in adipose tissue, is discussed.


1984 ◽  
Vol 247 (4) ◽  
pp. E526-E533
Author(s):  
A. S. Jennings

The effect of diabetes on 3,5,3'-triiodothyronine (T3) production was determined in the isolated perfused rat liver. Induction of diabetes with streptozotocin resulted in decreased serum thyroxine (T4) and T3 levels and a progressive decline in hepatic T3 production over 5 days. The decline in T3 production resulted from decreased conversion of T4 to T3, whereas T4 uptake was unchanged. Insulin administration restored serum T4 and T3, hepatic conversion of T4 to T3, and T3 production to normal levels. When serum T4 levels in diabetic rats were maintained by T4 administration, the conversion of T4 to T3 and T3 production returned to control levels. However, restoration of serum T4 levels in fasted rats failed to correct the decrease in hepatic T4 uptake or T3 production. Glucagon, at supraphysiological concentrations in vitro and in vivo, slightly decreased T4 uptake and T3 production without altering the conversion of T4 to T3. These data suggest that the fall in serum T4 levels observed in diabetic rats is important in mediating the decreased hepatic conversion of T4 to T3 and T3 production.


1990 ◽  
Vol 68 (12) ◽  
pp. 1393-1401 ◽  
Author(s):  
Victor S. Sauro ◽  
Kenneth P. Strickland

The role that diacylglycerol acyltransferase (DAGAT) may play in the switch in lipid metabolism from predominantly triacylglycerol- and phospholipid-synthesizing myoblasts to predominantly phospholipid-synthesizing myotubes has been studied during L6 skeletal myogenesis. Fatty acid induced triacylglycerol (TAG) accumulation in vivo was found to be optimal with long-chain, unsaturated fatty acids. The fatty acid induced TAG accumulation was significantly greater in myoblasts than that in myotubes. DAGAT activity in vitro was found to be associated with the particulate (membrane) fraction only. The inhibition by many thiol-specific reagents (N-ethylmaleimide, p-chloromercuribenzoate, iodoacetate, 5,5′-dithiobis(2-nitrobenzoic acid)) suggest that a thiol group is at or near the active site. In general, optimal DAGAT activity in vitro was observed when long-chain unsaturated acyl-CoAs and diacylglycerols (DAGs) containing long acyl chains were used as substrates for in vitro TAG synthesis (although 1,2-didecanoin was also very effective). DAGAT activity (expressed relative to DNA) was shown to decline over twofold during skeletal myogenesis when measured in the absence of exogenous DAG. However, in the presence of exogenous (1 mM) DAG, there was no significant change in DAGAT activity, suggesting that the levels of this enzyme are not altered during skeletal myogenesis. These results indicate that endogenous DAG levels are limiting TAG synthesis in L6 myotubes. However, DAG content of myotubes was significantly greater than that of myoblasts, suggesting that there may be an increased competition for DAG (perhaps owing to enhanced phospholipid synthesis) during skeletal myogenesis. The combined effects of decreased synthesis and increased degradation (reported earlier) of TAG may account for the decrease in endogenous TAG contents observed during skeletal myogenesis.Key words: diacylglycerol acyltransferase, TAG synthesis, skeletal myogenesis.


1991 ◽  
Vol 277 (3) ◽  
pp. 723-728 ◽  
Author(s):  
L B Tijburg ◽  
C B Nyathi ◽  
G W Meijer ◽  
M J H Geelen

Partially hepatectomized rats were used to investigate the mechanism of fatty-liver development in the regenerating rat liver. After partial hepatectomy the amount of hepatic triacylglycerol increased by almost 4-fold compared with sham-operated rats. The activities of both cytosolic and microsomal phosphatidate phosphohydrolase were enhanced at 12 h after surgery. The activity of diacylglycerol acyltransferase was increased at a later stage of regeneration. Analysis of plasma lipoproteins showed a significant decrease of lipids associated with very-low-density lipoproteins (VLDL). Relative to control, the rate of hepatic triacylglycerol synthesis from [3H]glycerol in vivo was stimulated at 22 h after partial liver resection. However, secretion of glycerol-labelled triacylglycerol in VLDL was the same in control and hepatectomized rats. In cultures of hepatocytes from hepatectomized donor rats, the concentration of triacylglycerol and the biosynthesis of this lipid from [3H]glycerol or from [3H]oleate were enhanced. The secretion of total triacylglycerol into the medium was not affected, resulting in a net accumulation of intracellular triacylglycerol. The rate of secretion of leucine-labelled apolipoproteins B and E associated with VLDL was similar in cell cultures from hepatectomized and sham-operated rats. The results of this study show that the enhancement of the biosynthesis of triacylglycerol in hepatectomized livers is not accompanied by an increase of the secretion of VLDL.


1990 ◽  
Vol 123 (1) ◽  
pp. 67-71 ◽  
Author(s):  
Liv S. Bjørn-Hansen Gøtzsche ◽  
Ole Gøtzsche ◽  
Allan Flyvbjerg ◽  
Niels Boye

Abstract. In order to elucidate the day-by-day development of low T3 syndrome, we made rats diabetic by an injection of streptozotocin. Untreated controls killed at day 0 and rats treated for 8 days with insulin after they had received streptozotocin served as controls. Subgroups of animals were killed 1, 2, 3, 4 and 8 days after streptozotocin. In serum, heart and liver, T3 was depressed to less than 50% of controls at day 4, whereas the insulin-treated rats differed from controls only as to heart T3. Heart iodothyronine 5'-deiodinase activity was depressed to a minimum at day 3 and depression was not prevented by insulin. Liver iodothyronine 5'-deiodinase activity had not reached a minimum at day 8, and again, insulin treatment did not normalize this parameter. T3 contents and iodothyronine 5'-deiodinase activity in brown adipose tissue did not differ from values in controls at any point of time. Thus, in the rats with low T3 syndrome induced by streptozotocin-diabetes, a lowered iodothyronine 5'-deiodinase activity is not fully inhibited by insulin treatment, whereas the T3 content in the liver is re-established during an observation period of 8 days. A direct toxic effect of streptozotocin seems unlikely as an in vitro study showed no influenze of streptozotocin on iodothyronine 5'-deiodinase activity in the liver. The study thus indicates that iodothyronine 5'-deiodinase activity in the heart and liver is depressed in experimental diabetes, despite near optimal regulation of blood glucose, and we suggest that lowered intracellular T3 production could, after some time, result in a hypothyroid state in different tissues.


Author(s):  
Hassan Ahmadvand ◽  
Majid Tavafi ◽  
Ali Khosrowbeygi ◽  
Gholamreza Shahsavari ◽  
Maryam Hormozi ◽  
...  

2014 ◽  
Vol 92 (5) ◽  
pp. 405-417 ◽  
Author(s):  
Xian-Wei Li ◽  
Yan Liu ◽  
Wei Hao ◽  
Jie-Ren Yang

Sequoyitol decreases blood glucose, improves glucose intolerance, and enhances insulin signaling in ob/ob mice. The aim of this study was to investigate the effects of sequoyitol on diabetic nephropathy in rats with type 2 diabetes mellitus and the mechanism of action. Diabetic rats, induced with a high-fat diet and a low dose of streptozotocin, and were administered sequoyitol (12.5, 25.0, and 50.0 mg·(kg body mass)−1·d−1) for 6 weeks. The levels of fasting blood glucose (FBG), serum insulin, blood urea nitrogen (BUN), and serum creatinine (SCr) were measured. The expression levels of p22phox, p47phox, NF-κB, and TGF-β1 were measured using immunohistochemisty, real-time PCR, and (or) Western blot. The total antioxidative capacity (T-AOC), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were also determined. The results showed that sequoyitol significantly decreased FBG, BUN, and SCr levels, and increased the insulin levels in diabetic rats. The level of T-AOC was significantly increased, while ROS and MDA levels and the expression of p22phox, p47phox, NF-κB, and TGF-β1 were decreased with sequoyitol treatment both in vivo and in vitro. These results suggested that sequoyitol ameliorates the progression of diabetic nephropathy in rats, as induced by a high-fat diet and a low dose of streptozotocin, through its glucose-lowering effects, antioxidant activity, and regulation of TGF-β1 expression.


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