Regulation of muscle malonyl-CoA levels in the nutritionally insulin-resistant desert gerbil,Psammomys obesus

2002 ◽  
Vol 18 (3) ◽  
pp. 217-223 ◽  
Author(s):  
Eleazar Shafrir ◽  
Ehud Ziv ◽  
Asish K. Saha ◽  
Neil B. Ruderman
Keyword(s):  
Psammomys Obesus ◽  
Insulin Resistant ◽  
Malonyl Coa ◽  
Desert Gerbil

Peroxisomal-mitochondrial oxidation in a rodent model of obesity-associated insulin resistance

2007 ◽  
Vol 293 (4) ◽  
pp. E986-E1001 ◽  
Author(s):  
Robert C. Noland ◽  
Tracey L. Woodlief ◽  
Brian R. Whitfield ◽  
Steven M. Manning ◽  
Jasper R. Evans ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Clinical Importance ◽  
Product Distribution ◽  
Zucker Rats ◽  
Acid Oxidation ◽  
Insulin Resistant ◽  
Malonyl Coa ◽  
Skeletal Muscle Lipid ◽  
Mitochondrial Oxidation ◽  
Cpt I

Peroxisomal oxidation yields metabolites that are more efficiently utilized by mitochondria. This is of potential clinical importance because reduced fatty acid oxidation is suspected to promote excess lipid accumulation in obesity-associated insulin resistance. Our purpose was to assess peroxisomal contributions to mitochondrial oxidation in mixed gastrocnemius (MG), liver, and left ventricle (LV) homogenates from lean and fatty ( fa/fa) Zucker rats. Results indicate that complete mitochondrial oxidation (CO2production) using various lipid substrates was increased approximately twofold in MG, unaltered in LV, and diminished ∼50% in liver of fa/fa rats. In isolated mitochondria, malonyl-CoA inhibited CO2production from palmitate 78%, whereas adding isolated peroxisomes reduced inhibition to 21%. These data demonstrate that peroxisomal products may enter mitochondria independently of CPT I, thus providing a route to maintain lipid disposal under conditions where malonyl-CoA levels are elevated, such as in insulin-resistant tissues. Peroxisomal metabolism of lignoceric acid in fa/fa rats was elevated in both liver and MG (LV unaltered), but peroxisomal product distribution varied. A threefold elevation in incomplete oxidation was solely responsible for increased hepatic peroxisomal oxidation (CO2unaltered). Alternatively, only CO2was detected in MG, indicating that peroxisomal products were exclusively partitioned to mitochondria for complete lipid disposal. These data suggest tissue-specific destinations for peroxisome-derived products and emphasize a potential role for peroxisomes in skeletal muscle lipid metabolism in the obese, insulin-resistant state.

Disorders in AMPK and Insulin Signalling Pathways in the Intestine of Insulin-Resistant and Diabetic Psammomys Obesus

2011 ◽  
Vol 140 (5) ◽  
pp. S-544 ◽  
Author(s):  
Elodie Harmel ◽  
Ali Bendjoudi ◽  
Mounib Elchebly ◽  
Benoit Viollet ◽  
Ehud Ziv ◽  
...  
Keyword(s):  
Insulin Signalling ◽  
Signalling Pathways ◽  
Psammomys Obesus ◽  
Insulin Resistant

Lipid abnormalities in tissues of the KKAy mouse: effects of pioglitazone on malonyl-CoA and diacylglycerol

1994 ◽  
Vol 267 (1) ◽  
pp. E95-E101 ◽  
Author(s):  
A. K. Saha ◽  
T. G. Kurowski ◽  
J. R. Colca ◽  
N. B. Ruderman
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Control Group ◽  
Insulin Resistant ◽  
Kkay Mice ◽  
Malonyl Coa ◽  
Tissue Lipids ◽  
Lipid Abnormalities ◽  
Diabetes And Obesity

Insulin resistance is present in liver and muscle of subjects with type 2 diabetes and obesity. Recent studies suggest that such insulin resistance could be related to abnormalities in lipid-mediated signal transduction; however, the nature of these abnormalities is unclear. To examine this question further, tissue levels of diacylglycerol (DAG), malonyl-CoA, and triglyceride (TG) were determined in liver and soleus muscle of obese insulin-resistant KKAy mice and lean C57 BL control mice. In addition, the effects of treatment with pioglitazone, an antidiabetic agent that acts by increasing insulin sensitivity in muscle, liver, and other tissues, were assessed. The KKAy mice were hyperglycemic (407 vs. 138 mg/dl), hypertriglyceridemic (337 vs. 109 mg/dl), hyperinsulinemic (631 vs. 15 mU/ml), and weighed more (42 vs. 35 g) than the control mice. They also had 1.5- to 2.0-fold higher levels of malonyl-CoA in both liver and muscle, higher DAG (twofold) and TG (1.3-fold) levels in muscle, and higher TG (threefold), but not DAG, levels. Treatment of the KKAy mice with pioglitazone for 4 days decreased plasma glucose, TGs, and insulin by approximately 50% and restored hepatic and muscle malonyl-CoA levels to control values. In contrast, pioglitazone increased hepatic and muscle DAG levels two- or threefold. It has no effect on muscle or hepatic TG content, and it slightly increased hepatic TGs in the control group. The results indicate that abnormalities in tissue lipids occur in both liver and muscle of the KKAy mouse and that they are differentially altered when insulin sensitivity is enhanced by treatment with pioglitazone.(ABSTRACT TRUNCATED AT 250 WORDS)

Potential mechanisms and consequences of cardiac triacylglycerol accumulation in insulin-resistant rats

2003 ◽  
Vol 284 (5) ◽  
pp. E923-E930 ◽  
Author(s):  
Laura L. Atkinson ◽  
Ray Kozak ◽  
Sandra E. Kelly ◽  
Arzu Onay-Besikci ◽  
James C. Russell ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Metabolism ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Fatty Acid Binding ◽  
Insulin Resistant ◽  
Lean Control ◽  
Malonyl Coa ◽  
Significant Difference ◽  
Ampk Activity

The accumulation of intracellular triacylglycerol (TG) is highly correlated with muscle insulin resistance. However, it is controversial whether the accumulation of TG is the result of increased fatty acid supply, decreased fatty acid oxidation, or both. Because abnormal fatty acid metabolism is a key contributor to the pathogenesis of diabetes-related cardiovascular dysfunction, we examined fatty acid and glucose metabolism in hearts of insulin-resistant JCR:LA-cp rats. Isolated working hearts from insulin-resistant rats had glycolytic rates that were reduced to 50% of lean control levels ( P < 0.05). Cardiac TG content was increased by 50% ( P < 0.05) in the insulin-resistant rats, but palmitate oxidation rates remained similar between the insulin-resistant and lean control rats. However, plasma fatty acids and TG levels, as well as cardiac fatty acid-binding protein (FABP) expression, were significantly increased in the insulin-resistant rats. AMP-activated protein kinase (AMPK) plays a major role in the regulation of cardiac fatty acid and glucose metabolism. When activated, AMPK increases fatty acid oxidation by inhibiting acetyl-CoA carboxylase (ACC) and reducing malonyl-CoA levels, and it decreases TG content by inhibiting glycerol-3-phosphate acyltransferase (GPAT), the rate-limiting step in TG synthesis. The activation of AMPK also stimulates cardiac glucose uptake and glycolysis. We thus investigated whether a decrease in AMPK activity was responsible for the reduced cardiac glycolysis and increased TG content in the insulin-resistant rats. However, we found no significant difference in AMPK activity. We also found no significant difference in various established downstream targets of AMPK: ACC activity, malonyl-CoA levels, carnitine palmitoyltransferase I activity, or GPAT activity. We conclude that hearts from insulin-resistant JCR:LA-cp rats accumulate substantial TG as a result of increased fatty acid supply rather than from reduced fatty acid oxidation. Furthermore, the accumulation of cardiac TG is associated with a reduction in insulin-stimulated glucose metabolism.

Metabolic and anti-atherogenic effects of long-term benfluorex in dyslipidemic insulin-resistant sand rats (Psammomys obesus)

Life Sciences ◽  
1998 ◽  
Vol 63 (1) ◽  
pp. 65-76 ◽  
Author(s):  
G. Marquié ◽  
T. El Madani ◽  
M.L. Solera ◽  
M.T. Pieraggi ◽  
P. Hadjiisky ◽  
...  
Keyword(s):  
Psammomys Obesus ◽  
Insulin Resistant

Vascular responses to α-adrenergic stimulation and depolarization are enhanced in insulin-resistant and diabetic Psammomys obesus

2003 ◽  
Vol 81 (7) ◽  
pp. 704-710 ◽  
Author(s):  
M Zoltowska ◽  
J St-Louis ◽  
E Ziv ◽  
B Sicotte ◽  
E E Delvin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vascular Reactivity ◽  
Vascular Complications ◽  
Psammomys Obesus ◽  
Adrenergic Stimulation ◽  
Endothelial Lining ◽  
Insulin Resistant ◽  
Group A ◽  
Group B ◽  
Endothelium Dependent Relaxation

Since vascular complications often accompany diabetes, we examined the influence of the endothelial lining on vascular reactivity in Psammomys obesus, a desert gerbil that acquires insulin resistance and diabetes when exposed to a laboratory diet. Vasoconstriction to phenylephrine and depolarizing KCl, as well as carbachol endothelium-dependent relaxation, were assessed in rings of thoracic aortae obtained from three groups: (i) group A, normoglycemic–normoinsulinemic; (ii) group B, normoglycemic–hyperinsulinemic, and (iii) group C, hyperglycemic–hyperinsulinemic animals. As expected, marked hypertriglyceridemia and hypercholesterolemia characterized groups B and C, which developed enhanced contractile responsiveness to phenylephrine and KCl compared with controls (group A). Furthermore, both experimental groups displayed a significant decrease in endothelium-dependent relaxation to carbachol. Altered lipid profiles are considered to play some role in the observed modification of aortic reactivity. Overall, our data indicate that vascular contractile responsiveness is enhanced early in the development of insulin resistance and diabetes in the female P. obesus.Key words: insulin resistance, diabetes, vascular reactivity, LDL-cholesterol, hypertriglyceridemia.

Lipid Abnormalities in Muscle of Insulin-resistant Rodents The Malonyl CoA Hypothesis

1997 ◽  
Vol 827 (1 Lipids and Sy) ◽  
pp. 221-230 ◽  
Author(s):  
N. B. RUDERMAN ◽  
A. K. SAHA ◽  
D. VAVVAS ◽  
S. J. HEYDRICK ◽  
T. G. KUROWSKI
Keyword(s):  
Insulin Resistant ◽  
Malonyl Coa ◽  
Lipid Abnormalities

Malonyl CoA fuel sensing mechanism in muscle of insulin resistant rodents

2009 ◽  
Vol 105 (S 03) ◽  
pp. 15-15
Author(s):  
Neil B. Ruderman ◽  
Asish K. Saha ◽  
Demetrios Vavvas ◽  
Theodore Kurowski ◽  
D. Ross Laybutt ◽  
...  
Keyword(s):  
Sensing Mechanism ◽  
Insulin Resistant ◽  
Malonyl Coa
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