NREP Bridges TGF-ß Signaling and Lipid Metabolism in the Epigenetic Reprogramming of NAFLD in the Offspring of Insulin-Resistant Parents

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 46-OR
Author(s):  
DARIO F. DE JESUS ◽  
KAZUKI ORIME ◽  
CHIH-HAO WANG ◽  
JIANG HU ◽  
ERCUMENT DIRICE ◽  
...  
1996 ◽  
Vol 270 (2) ◽  
pp. E344-E352 ◽  
Author(s):  
A. T. Ozcelikay ◽  
D. J. Becker ◽  
L. N. Ongemba ◽  
A. M. Pottier ◽  
J. C. Henquin ◽  
...  

Molybdenum mimics certain insulin actions in vitro. We have investigated the effects of oral administration of Na2MoO4 (Mo) for 8 wk on carbohydrate and lipid metabolism in streptozotocin-diabetic rats. Mo decreased hyperglycemia and glucosuria by 75% and corrected the elevation of plasma nonesterified fatty acids. Tolerance to glucose loads was improved, and glycogen stores were replenished. These effects were not due to a rise of insulinemia. In liver, Mo restored the blunted mRNA and activity of glucokinase and pyruvate kinase and decreased to normal phosphoenolpyruvate carboxykinase values. Finally, Mo totally reversed the low expression and activity of acetyl-CoA carboxylase and fatty acid synthase in liver, but not in white adipose tissue. In conclusion, Mo exerts a marked blood glucose-lowering effect in diabetic rats by an insulin-like action. This effect results in part from a restoration of hepatic glucose metabolism and is associated with a tissue-specific correction of lipogenic enzyme gene expression, both processes being essentially mediated by reversal of impaired pretranslational regulatory mechanisms. These observations raise new therapeutic perspectives in diabetes, particularly in the insulin-resistant condition.


2003 ◽  
Vol 133 (1) ◽  
pp. 127-133 ◽  
Author(s):  
Adriana Chicco ◽  
María Eugenia D'Alessandro ◽  
Liliana Karabatas ◽  
Claudia Pastorale ◽  
Juan Carlos Basabe ◽  
...  

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 273-279 ◽  
Author(s):  
Naoichi Sato ◽  
Kunihisa Kobayashi ◽  
Toyoshi Inoguchi ◽  
Noriyuki Sonoda ◽  
Minako Imamura ◽  
...  

The adipocyte-derived hormone resistin has been proposed as a possible link between obesity and insulin resistance in murine models. Many recent studies have reported physiological roles for resistin in glucose homeostasis, one of which is enhancement of glucose production from the liver by up-regulating gluconeogenic enzymes such as glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. However, its in vivo roles in lipid metabolism still remain to be clarified. In this study, we investigated the effects of resistin overexpression on insulin action and lipid metabolism in C57BL/6 mice using an adenoviral gene transfer technique. Elevated plasma resistin levels in mice treated with the resistin adenovirus (AdmRes) were confirmed by Western blotting analysis and RIAs. Fasting plasma glucose levels did not differ between AdmRes-treated mice and controls, but the basal insulin concentration was significantly elevated in AdmRes-treated mice. In AdmRes-treated mice, the glucose-lowering effect of insulin was impaired, as evaluated by insulin tolerance tests. Furthermore, total cholesterol and triglyceride concentrations were significantly higher, whereas the high-density lipoprotein cholesterol level was significantly lower. Lipoprotein analysis revealed that low-density lipoprotein was markedly increased in AdmRes-treated mice, compared with controls. In addition, in vivo Triton WR-1339 studies showed evidence of enhanced very low-density lipoprotein production in AdmRes-treated mice. The expressions of genes involved in lipoprotein metabolism, such as low-density lipoprotein receptor and apolipoprotein AI in the liver, were decreased. These results suggest that resistin overexpression induces dyslipidemia in mice, which is commonly seen in the insulin-resistant state, partially through enhanced secretion of lipoproteins.


2000 ◽  
Vol 167 (3) ◽  
pp. 525-531 ◽  
Author(s):  
D Patiag ◽  
X Qu ◽  
S Gray ◽  
I Idris ◽  
M Wilkes ◽  
...  

Angiotensin II (ANGII) increases insulin sensitivity in diabetic and non-diabetic subjects, even at subpressor doses, and because there is 'crosstalk' between ANGII and insulin-signaling pathways the underlying mechanism may not be due solely to changes in regional blood flow. A series of experimental studies was undertaken to evaluate the effects of ANGII on glucose and lipid metabolism in vivo and in vitro. Groups of fructose-fed, insulin-resistant Sprague-Dawley (SD) rats were pre-treated with 0.3 mg/kg per day of the AT(1)-receptor antagonist L-158 809 (n=16), or vehicle (n=16), by oral gavage. This was prior to an oral glucose tolerance test (day 5) and measurement of the effects of ANGII infusion (20 ng/kg per min i.v. for 3 h) on whole-body insulin sensitivity using the insulin suppression test (day 7). The effect of ANGII infusion on total triglyceride secretion rate (TGSR) was evaluated in normal SD rats pretreated for 7 days with L-158 809 (n=12) or vehicle (n=12). AT(1)- and AT(2)- receptor mRNA expression and [(3)H]2-deoxyglucose uptake were assessed in cultured L6 myoblasts. Short-term treatment with L-158 809 had no effect on glucose tolerance or fasting triglyceride levels in fructose-fed rats. ANGII infusion had no effect on insulin sensitivity in fructose-fed rats pretreated with vehicle (steady-state plasma glucose (SSPG) values 8.1+/-1.6 vs 8. 4+/-0.4 mmol/l), but pretreatment with L-158 809 resulted in ANGII having a modest insulin antagonist effect in this insulin-resistant model (SSPG values 9.6+/-0.3 vs 7.1+/-0.6, P<0.03). ANGII infusion had no significant effect on TGSR (e.g. 24.6+/-1.4 vs 28.4+/-0.9 mg/100 g per h in vehicle-treated animals). RT-PCR analysis showed that L6 cells express both AT(1)- and AT(2)-receptor mRNA. Incubation with ANGII (10(-9) and 10(-8) M) had no significant effect on the dose-response curve for insulin-stimulated [(3)H]2-deoxyglucose uptake. For example, C(I200) values (dose of insulin required to increase glucose uptake by 200%) were 4.5 x 10(-9) M (control) vs 3.9 x 10(-9) M and 6.2 x 10(-9) M, whereas the positive control (glucagon-like peptide-1) increased insulin sensitivity. Thus, ANGII infusion may have a modest insulin antagonist effect on glucose disposal in insulin-resistant fructose-fed rats pretreated with an AT(1)-blocker, but ANGII has no effect on TGSR or in vitro glucose uptake in L6 myoblasts. These findings are relevant to recent clinical discussions about the metabolic effects of ANGII and renin-angiotensin system blockade.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Jinnan Li ◽  
Jinlei Feng ◽  
Hong Wei ◽  
Qunying Liu ◽  
Ting Yang ◽  
...  

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia and dyslipidemia caused by impaired insulin secretion and resistance of the peripheral tissues. A major pathogenesis of T2DM is obesity-associated insulin resistance. Gynura divaricata (L.) DC. (GD) is a natural plant and has been reported to have numerous health-promoting effects on both animals and humans. In this study, we aimed to elucidate the regulatory mechanism of GD improving glucose and lipid metabolism in an obesity animal model induced by high-fat and high-sugar diet in combination with low dose of streptozocin and an insulin-resistant HepG2 cell model induced by dexamethasone. The study showed that the water extract of GD (GD extract A) could significantly reduce fasting serum glucose, reverse dyslipidemia and pancreatic damage, and regulate the body weight of mice. We also found that GD extract A had low toxicity in vivo and in vitro. Furthermore, GD extract A may increase glucose consumption in insulin-resistant HepG2 cells, markedly inhibit NF-κB activation, and decrease the impairment in signaling molecules of insulin pathway, such as IRS-1, AKT, and GLUT1. Overall, the results indicate that GD extract A is a promising candidate for the prevention and treatment of T2DM.


Lipids ◽  
2006 ◽  
Vol 41 (2) ◽  
pp. 179-188 ◽  
Author(s):  
Amy Noto ◽  
Peter Zahradka ◽  
Natalia Yurkova ◽  
Xueping Xie ◽  
Evan Nitschmann ◽  
...  

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