scholarly journals Regulation of phosphoenolpyruvate carboxykinase (GTP) in adipose tissue in vivo by glucocorticoids and insulin

1976 ◽  
Vol 158 (1) ◽  
pp. 1-7 ◽  
Author(s):  
O Meyuhas ◽  
L Reshef ◽  
J M Gunn ◽  
R W Hanson ◽  
F J Ballard

1. The regulation of the synthesis of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) in epididymal adipose tissue, liver and kidney in vivo was studied immunochemically. 2. Phosphoenolpyruvate carboxykinase (GTP) synthesis in adipose tissue is increased by starvation, diabetes and noradrenaline, and decreased by re-feeding and insulin. These changes were also seen in adrenalectomized rats and are qualitatively similar to those observed for the liver enzyme. This indicates the involvement of cyclic AMP as an inducer and insulin as a de-inducer in the regulation of phosphoenolpyruvate carboxykinase (GTP) in both tissues. (Induction and de-induction are defined as selective increase and decrease respectively in the rate of enzyme synthesis, regardless of the mechanism involved.)3. Adrenalectomy had little effect on phosphoenolpyruvate carboxykinase (GTP) synthesis in liver and kidney, but increased the synthesis rate of the adipose-tissue enzyme. Starvation and adrenalectomy had additive effects in increasing the synthesis rate of adipose-tissue phosphoenolpyruvate carboxykinase (GTP). In adrenalectomized diabetic rats glucocorticoids increased phosphoenolpyruvate carboxykinase (GTP) synthesis in liver and kidney while decreasing enzyme synthesis in adipose tissue. De-induction of adipose tissue phosphoenolpyruvate carboxykinase (GTP) is therefore regulated independently by glucocorticoids and insulin. 4. Although liver, kidney and adipose-tissue phosphoenolpyruvate carboxykinases (GTP) are seemingly identical, there is an apparent tissue-specific differentiation in regulatory systems for the enzyme.

1976 ◽  
Vol 158 (1) ◽  
pp. 9-16 ◽  
Author(s):  
O Meyuhas ◽  
L Reshef ◽  
F J Ballard ◽  
R W Hanson

1. Epididymal adipose tissue from the rat was maintained in culture for periods of up to 96h. 2. After an initial decrease in protein synthesis during the first 24h of culture, the adipose tissue recovered its capacity to synthesize and accumulate proteins of a relatively large size. 3. The activity of phosphoenolpyruvate carboxykinase decreased in a parallel manner, but increased again after 24h of incubation of the tissue in culture, to a value twice that noted in the tissue in vivo. This increase in enzyme activity was due to an increase in its rate of synthesis. 4. Both insulin and dexamethasone (9alpha-fluoro-16alpha-methyl-11beta,17,-21-trihydroxypregna-1,4-diene-3,20-dione) inhibited phosphoenolpyruvate carboxykinase synthesis, but dexamethasone also decreased total protein synthesis. 5. The half-life of phosphoenolpyruvate carboxykinase in adipose tissue cultured in vitro was 5-7h and was not altered by insulin or dexamethasone. 6. It is concluded that both insulin and glucocroticoids lower the activity of phosphoenolpyruvate carboxykinase in rat adipose tissue by decreasing its rate of synthesis.


1975 ◽  
Vol 152 (2) ◽  
pp. 401-408 ◽  
Author(s):  
Christopher I. Pogson ◽  
Stephen A. Smith

1. Phosphoenolpyruvate carboxykinase was assayed by three methods: (i) incorporation of H14CO3- into oxaloacetate: (ii) conversion of oxaloacetate into phosphoenolpyruvate, subsequently assayed enzymically; and (iii) transfer of 32P from [γ-32P]GTP to oxaloacetate. 2. Enzyme activity is increased in liver and epididymal adipose tissue in alloxan-diabetes and starvation, and in kidney in starved, acidotic and steroid-treated animals. 3. The ratios of the ‘back’ to the ‘forward’ reactions in liver, kidney and epididymal adipose tissue are different and characteristic of each tissue; they differ markedly from values reported for the purified mitochondrial enzyme. 4. The ratio of the ‘back’ to ‘forward’ reaction in any one tissue is constant in adrenalectomized, diabetic, acidotic and steroid-treated animals. 5. In starved animals, the ratio is increased in liver and kidney, but decreased in epididymal adipose tissue. 6. Administration of l-tryptophan results in an acute (1h) increase in activity measured in the ‘forward’ direction alone in liver and epididymal adipose tissue, but not in kidney.


1975 ◽  
Vol 150 (2) ◽  
pp. 195-203 ◽  
Author(s):  
J M Gunn ◽  
R W Hanson ◽  
O Meyuhas ◽  
L Reshef ◽  
F J Ballard

The effect glucocorticoids on the synthesis and degradation of phosphoenolpyruvate carboxykinase (GTP)(EC4.1.1.32) in rat liver and kidney in vivo was studied immunochemically. The glucocorticoid analogue triamcinolone (9α-fluoro-11β, 21-dihydroxy-16α,17α-isopropylidenedioxypregna-1,4-diene-3,20-dione) increased the synthesis rate of the kidney enzyme in starved animals. Both triamcinolone and cortisol decreased the synthesis rate of hepatic phosphoenolpyruvate carboxykinase (GTP) in fed and starved rats, but were without effect on the degradation rate of the enzyme. This effect of triamcinolone in liver was reversed by injection of dibutyryl cyclic AMP. However, in diabetic animals glucocorticoids increased the synthesis rate of hepatic phosphoenolpyruvate carboxykinase (GTP). Triamcinolone administration to starved rats in vivo is shown to cause an increase in the portal blood concentrations of insulin and glucose. Since the physiological de-inducer of liver phosphoenolpyruvate carboxykinase (GTP) is insulin, this is the probable cause of the decrease in the synthesis rate of the hepatic enzyme noted when glucocorticoids are administered to non-diabetic animals.


1971 ◽  
Vol 124 (3) ◽  
pp. 615-621 ◽  
Author(s):  
Mitchell L. Halperin

The effect of insulin on the conversion of pyruvate into fatty acids in the presence and in the absence of glucose was studied in epididymal adipose tissue of the rat. 1. In adipose tissue from the normal rat, conversion of pyruvate into fatty acids is directly related to its concentration, the maximal rates occurring with 40mm- and the half-maximal rates with approx. 4mm-pyruvate. Insulin treatment did not greatly influence the maximal rates, but the half-maximal rates were at much lower pyruvate concentrations. This effect of insulin could be seen with physiological concentrations of this hormone (50–100μunits/ml). 2. In adipose tissue from acute-alloxan-diabetic and 36h-starved rats the conversion of pyruvate into fatty acids was almost zero until its concentration exceeded 3mm and then increased markedly as the concentration of pyruvate was increased. The lag phase of this S-shaped curve was decreased but not eliminated when insulin was present. This could account for the very low rates of glucose conversion into fatty acids in these metabolic states. Maximum rates of fatty acid synthesis were similar in the presence and in the absence of insulin, but only when 30–40mm-pyruvate was employed. Re-feeding of the starved rats or insulin treatment of the diabetic rats in vivo for several days restored these patterns to normal.


Drug Research ◽  
2018 ◽  
Author(s):  
Bijan Oskouei ◽  
Soheil Abbaspour-Ravasjani ◽  
Seyed Jamal Musavinejad ◽  
Seyed Ahmad Salehzadeh ◽  
Alireza Abdolhosseinzadeh ◽  
...  

1964 ◽  
Vol 207 (6) ◽  
pp. 1215-1220 ◽  
Author(s):  
Alisa Gutman ◽  
Eleazar Shafrir

Rat adipose tissue from different body sites was shown to contain uridine diphosphoglucose (UDPG)-transglucosylase activity, which on the basis of protein content was comparable to or higher than that reported for muscle or liver. In epididymal adipose tissue, the activity of UDPG-glycogen transglucosylase and phosphorylase, as well as the content of glycogen per wet weight, decreased with increasing age of the animals in parallel with the decrease of tissue protein content. On prolonged fast the activity of UDPG-glycogen transglucosylase and phosphorylase per milligram protein dropped by 25–50% of the control value. On refeeding, the extent of changes was variable but, in general, at 24 hr control or higher levels of activity were reached and at 48 hr the activities were elevated. The ratio of glucose 6-phosphate independent activity of UDPG-glycogen transglucosylase to total activity was not affected by fasting and refeeding or by the administration of glucose with insulin. In adrenalectomized rats, with high adipose tissue glycogen, no change in UDPG-glycogen transglucosylase was found, whereas the levels of phosphorylase were elevated. Epinephrine in vivo and in vitro did not affect the activity of UDPG-glycogen transglucosylase of adipose tissue.


1986 ◽  
Vol 250 (5) ◽  
pp. E530-E537
Author(s):  
R. Rabkin ◽  
G. M. Reaven ◽  
C. E. Mondon

The in vivo metabolism of insulin is a complex process in which liver, kidney, and muscle are major participants. In this study we evaluated the effect of spontaneous hyperglycemic nonketoacidotic diabetes (DH) and ketoacidotic diabetes (DKA) on insulin clearance and degradation by these organs. Livers, hindlimbs, and kidneys from nondiabetic controls and DH and DKA Bio-Breed rats were isolated and perfused with artificial media. Liver clearance of immunoreactive insulin (ml/min) was significantly higher in DH rats, 6.0 +/- 0.2, but significantly lower in DKA rats, 3.4 +/- 0.5, compared with controls, 4.6 +/- 0.2. Acidosis alone induced by ammonium chloride loading, did not impair liver insulin clearance (4.8 +/- 0.4 ml/min). Muscle responded differently to the diabetic state in that insulin clearance was not altered by DH and DKA. Renal (organ) clearance of insulin was significantly depressed in the DKA state when compared with controls (0.52 +/- 0.04 and 0.75 +/- 0.07 ml X min-1 X g-1, respectively). This could largely be explained by a lower glomerular filtration rate. Fractional urinary insulin clearance was increased twofold above control values in DH kidneys and fourfold in DKA kidneys, indicating that tubular luminal absorption of insulin was impaired in both states. By contrast contraluminal uptake (peritubular clearance) did not differ significantly from controls. 125I-insulin degrading activity of the 100,000 g supernate fraction from muscle homogenates was similar in the diabetic and control groups. However in liver and kidney, degrading activity did not correspond to whole organ insulin clearance in a consistent manner.(ABSTRACT TRUNCATED AT 250 WORDS)


1966 ◽  
Vol 44 (1) ◽  
pp. 47-57 ◽  
Author(s):  
James Campbell ◽  
G. R. Green

In normal Chinese hamsters (Cricetulus griseus) the mean concentration of free fatty acids (FFA) in serum varied from group to group, but was (i) consistently 4 to 9 times greater than in rats, dogs, or man; (ii) slightly higher than in Syrian hamsters; (iii) two- to four-fold higher than in fasting or alloxan-diabetic rats. The epididymal adipose tissue of the Chinese hamster (i) had initial concentrations of FFA comparable to those in the rat and Syrian hamster; (ii) released, in the same time interval, 8- to 10-fold more FFA in vitro than this tissue of the rat; (iii) had higher concentrations of FFA after incubation than the incubated tissue of the rat. The retroperitoneal (perirenal) adipose tissue of the Chinese hamster was less active in release of fatty acids in vitro than the epididymal, but was, however, more active than the epididymal adipose tissue of the rat. These characteristics of FFA metabolism in the Chinese hamster were apparently attributable to species, not to age, diet, or sex. In the Chinese hamster, the weight of the epididymal adipose tissue per gram of body was relatively high. It appears that in this species the rate of release of fatty acids from adipose tissue is great, leading to high FFA concentrations in serum.In Chinese hamster and rat adipose tissues in vitro, glucose and insulin (separately) reduced the rate of release of FFA and the amount of FFA in the tissues, but glucose and insulin together produced the greatest reductions. The net reduction in FFA release by glucose and insulin in vitro was greater in tissue from the Chinese hamster. Insulin markedly increased glucose uptake by the adipose tissues of both species. The possible relation of the results to spontaneous diabetes in the Chinese hamster is discussed.


2006 ◽  
Vol 84 (6) ◽  
pp. 647-654 ◽  
Author(s):  
Sameer Mohammad ◽  
Asia Taha ◽  
Kamal Akhtar ◽  
R.N.K. Bamezai ◽  
Najma Zaheer Baquer

Plasma glucose levels are maintained by a precise balance between glucose production and its use. Liver pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK), 2 key enzymes of glycolysis and gluconeogenesis, respectively, play a crucial role in this glucose homeostasis along with skeletal muscle glucose transporter (GLUT4). In the diabetic state, this balance is disturbed owing to the absence of insulin, the principal factor controlling this regulation. In the present study, alloxan-diabetic animals having high glucose levels of more than 300 mmol/L have been taken and the administration of Trigonella seed powder (TSP) to the diabetic animals was assessed for its effect on the expression of PK and PEPCK in liver and GLUT4 distribution in skeletal muscle of alloxan-diabetic rats. TSP treatment to the diabetic animals resulted in a marked decrease in the plasma glucose levels. Trigonella treatment partially restored the altered expression of PK and PEPCK. TSP treatment also corrected the alterations in the distribution of GLUT4 in the skeletal muscle.


2018 ◽  
Vol 29 (5) ◽  
pp. 447-461 ◽  
Author(s):  
Azubuike P. Ebokaiwe ◽  
Omamuyovwi M. Ijomone ◽  
Oscar Edeh ◽  
Ifebunachi Oteh ◽  
David E. Ebuka

Abstract Background The use of Loranthus micranthus in folklore medicine for treatment of diabetes and its associated complications is a common practice around the world. The present study investigated this traditional affirmation by in vivo investigation into the effect of L. micranthus leaf extract on hepatic and renal, oxidative status and glucose metabolism in streptozotocin (STZ)-induced diabetic rats. Methods Diabetes mellitus was induced in adult male Wistar rats by intraperitoneal injection of STZ (60 mg/kg). The diabetic rats were thereafter treated orally once per day with 5 mg/kg gilbenclamide or L. micranthus leaf extract (100 or 200 mg/kg) and monitored for 14 days. Clinical observations, plasma biochemistry, hormonal profile, oxidative stress parameters, glucose metabolism enzymes and histopathologic examination of the liver and kidney were evaluated to monitor treatment-related effects of L. micranthus leaf extract in STZ-induced diabetic rats. Results Loranthus micranthus leaf extract administration significantly ameliorated hyperglycemia-mediated damage by decreasing the blood glucose level (45.9% and 84.7% on days 7 and 14 posttreatment, respectively), enhancing the antioxidant status, inhibiting lipid peroxidation and improving the architecture of the liver and kidney in STZ-induced diabetic rats. Furthermore, intervention of L. micranthus leaf extract restored the liver and kidney function biomarkers and increased the plasma levels of triiodothyronine and thyroxine to normal control in STZ-induced diabetic rats. Conclusions The findings from this investigation provide credible scientific support for the traditional use of L. micranthus leaf extract in the treatment of diabetes and its associated complications.


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