Abstract 240: Effect of Co-Administration of Simvastatin and Pioglitazone on Lipid Profile and Insulin Resistance in Insulin-Resistant Rats

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Abbas Mohammadi ◽  
Behnaz Danesh ◽  
Hossein Fallah
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Synergistic Effects ◽  
Treated Group ◽  
Serum Glucose ◽  
Insulin Resistant ◽  
Simvastatin Group ◽  
Significant Difference ◽  
Pioglitazone Group

Objective: Insulin resistance is characterized by hyperglycemia, dyslipidemia, hyperinsulinemia and hypertension. Also, in obesity, decreased plasma adiponectin and increased free fatty acids, are the main factors that correlate with insulin resistance. Thiazolidinediones, like pioglitazone are used to improve insulin sensitivity and ATPIII guidelines suggest statin therapy for correction of dyslipidemia in metabolic syndrome. In this study we evaluated co-administration of simvastatin and pioglitazone on insulin resistance in rats. Materials and Methods: Rats were randomly divided into five groups. After 6 weeks on a high-fructose diet, one group received simvastatin, one group received pioglitazone, and one received pioglitazone and simvastatin. After 2 weeks of treatment, animals were anesthetized with ether. Blood was collected from their heart. Liver, visceral adipose, and muscle tissues were collected and were immediately frozen. Serum glucose, TGs, cholesterol, insulin, adiponectin, and free fatty acids were measured. Expression of PPAR.γ and GLUT4 genes was checked by real-time PCR and Western blotting. Results: Only the results that showed a significant difference are shown. Blood glucose: pioglitazone group (129.1±5.8mg/dl), simvastatin-pioglitazone treated group (137.1±9.9 mg/dl); TG: simvastatin group (123.6±16.6 mg/dl), simvastatin-pioglitazone group (101.5±7.5 mg/dl); Insulin: pioglitazone group (40.27±2.75 p mol/l), simvastatin group (70.07±10.35 pmol/l), simvastatin-pioglitazone (47.62±2.8 pmol/l); Adiponectin: pioglitazone (5.90±0.29 μg/ml), simvastatin-pioglitazone (5.89±0.41μg/ml); HOMA-IR: pioglitazone (2.11±0.13), simvastatin (4.76±0.37), simvastatin-pioglitazone (2.70±0.29). In pioglitazone group, PPAR.γ expression at both mRNA and protein levels was significantly different from insulin resistant group. Conclusion: As the results show, simvastatin has beneficial effects on insulin resistance in rats. Pioglitazone did not show any synergistic effect with simvastatin, however, when used in combination with simvastatin, pioglitazone shows a synergistic effects in lowering TG and HOMAIR that potentially can lower diabetes complications.

The Relationship of Fasting Free Fatty Acids, Adipose Tissue, Insulin Resistance, and Fasting Glucose Concentrations with Subsequent ß-Cell Function in Nondiabetic Subjects

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1812-P
Author(s):  
MARIA D. HURTADO ◽  
J.D. ADAMS ◽  
MARCELLO C. LAURENTI ◽  
CHIARA DALLA MAN ◽  
CLAUDIO COBELLI ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Free Fatty Acids ◽  
Cell Function ◽  
Fasting Glucose ◽  
Relationship Of ◽  
The Relationship

Disruption of glucose homeostasis and induction of insulin resistance by elevated free fatty acids in human L02 hepatocytes

2009 ◽  
Vol 32 (5) ◽  
pp. 454-259 ◽  
Author(s):  
X. D. Wan ◽  
W. B. Yang ◽  
Y. Z. Xia ◽  
J. F. Wang ◽  
T. Lu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Glucose Homeostasis

scholarly journals Endothelial dysfunction precedes hypertension in diet-induced insulin resistance

1998 ◽  
Vol 275 (3) ◽  
pp. R788-R792 ◽  
Author(s):  
Prasad V. G. Katakam ◽  
Michael R. Ujhelyi ◽  
Margarethe E. Hoenig ◽  
Allison Winecoff Miller
Keyword(s):  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Serum Insulin ◽  
Serum Glucose ◽  
Mesenteric Arteries ◽  
Control Group ◽  
Sprague Dawley ◽  
Insulin Resistant ◽  
Glucose Levels

The insulin-resistant (IR) syndrome may be an impetus for the development of hypertension (HTN). Unfortunately, the mechanism by which this could occur is unclear. Our laboratory and others have described impaired endothelium-mediated relaxation in IR, mildly hypertensive rats. The purpose of the current study is to determine if HTN is most likely a cause or result of impaired endothelial function. Sprague-Dawley rats were randomized to receive a fructose-rich diet for 3, 7, 10, 14, 18, or 28 days or were placed in a control group. The control group received rat chow. After diet treatment, animals were instrumented with arterial cannulas, and while awake and unrestrained, their blood pressure (BP) was measured. Subsequently, endothelium-mediated relaxation to acetylcholine was determined (in vitro) by measuring intraluminal diameter of phenylephrine-preconstricted mesenteric arteries (∼250 μM). Serum insulin levels were significantly elevated in all groups receiving fructose feeding compared with control, whereas there were no differences in serum glucose levels between groups. Impairment of endothelium-mediated relaxation starts by day 14 [mean percent maximal relaxation (Emax): 69 ± 10% of baseline] and becomes significant by day 18 (Emax: 52 ± 11% of baseline; P < 0.01). However, the mean BP (mmHg) does not become significantly elevated until day 28 [BP: 132 ± 1 ( day 28) vs. 116 ± 3 (control); P < 0.05]. These findings demonstrate that both IR and endothelial dysfunction occur before HTN in this model and suggest that endothelial dysfunction may be a mechanism linking insulin resistance and essential HTN.

Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites

2006 ◽  
Vol 100 (5) ◽  
pp. 1467-1474 ◽  
Author(s):  
Jong Sam Lee ◽  
Srijan K. Pinnamaneni ◽  
Su Ju Eo ◽  
In Ho Cho ◽  
Jae Hwan Pyo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Polyunsaturated Fatty Acids ◽  
Glucose Uptake ◽  
High Fat ◽  
Insulin Resistant ◽  
L6 Myotubes ◽  
Lipid Metabolites

Consumption of a Western diet rich in saturated fats is associated with obesity and insulin resistance. In some insulin-resistant phenotypes this is associated with accumulation of skeletal muscle fatty acids. We examined the effects of diets high in saturated fatty acids (Sat) or n-6 polyunsaturated fatty acids (PUFA) on skeletal muscle fatty acid metabolite accumulation and whole-body insulin sensitivity. Male Sprague-Dawley rats were fed a chow diet (16% calories from fat, Con) or a diet high (53%) in Sat or PUFA for 8 wk. Insulin sensitivity was assessed by fasting plasma glucose and insulin and glucose tolerance via an oral glucose tolerance test. Muscle ceramide and diacylglycerol (DAG) levels and triacylglycerol (TAG) fatty acids were also measured. Both high-fat diets increased plasma free fatty acid levels by 30%. Compared with Con, Sat-fed rats were insulin resistant, whereas PUFA-treated rats showed improved insulin sensitivity. Sat caused a 125% increase in muscle DAG and a small increase in TAG. Although PUFA also resulted in a small increase in DAG, the excess fatty acids were primarily directed toward TAG storage (105% above Con). Ceramide content was unaffected by either high-fat diet. To examine the effects of fatty acids on cellular lipid storage and glucose uptake in vitro, rat L6 myotubes were incubated for 5 h with saturated and polyunsaturated fatty acids. After treatment of L6 myotubes with palmitate (C16:0), the ceramide and DAG content were increased by two- and fivefold, respectively, concomitant with reduced insulin-stimulated glucose uptake. In contrast, treatment of these cells with linoleate (C18:2) did not alter DAG, ceramide levels, and glucose uptake compared with controls (no added fatty acids). Both 16:0 and 18:2 treatments increased myotube TAG levels (C18:2 vs. C16:0, P < 0.05). These results indicate that increasing dietary Sat induces insulin resistance with concomitant increases in muscle DAG. Diets rich in n-6 PUFA appear to prevent insulin resistance by directing fat into TAG, rather than other lipid metabolites.

scholarly journals Are marine n-3 fatty acids protective towards insulin resistance? From cell to human

2020 ◽  
Vol 79 (4) ◽  
pp. 417-427 ◽  
Author(s):  
Jacques Delarue
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Protective Effect ◽  
Specific Effect ◽  
Experimental Models ◽  
Zucker Rats ◽  
Diabetic Patients ◽  
High Dose ◽  
Biochemical Alterations ◽  
Insulin Resistant

Marine n-3 fatty acids improve most of the biochemical alterations associated with insulin resistance (IR). Experimental models of dietary-induced IR in rodents have shown their ability (often at a very high dose) to prevent IR, but with sometimes a tissue specific effect. However, in a high sucrose diet-induced IR rat model, they are unable to reverse IR once installed; in other rodent models (dexamethasone, Zucker rats), they are inefficacious perhaps because of the severity of IR. The very low incidence of type-2 diabetes (T2D) in Inuits in the 1960s, which largely increased over the following decades in parallel to the replacement of their traditional marine food for a western diet strongly suggests a protective effect of marine n-3 towards the risk of T2D; this was confirmed by reversal of its incidence in intervention studies reintroducing their traditional food. In healthy subjects and insulin-resistant non-diabetic patients, most trials and meta-analyses conclude to an insulin-sensitising effect and to a very probable preventive or alleviating effect towards IR. Concerning the risk of T2D, concordant data allow us to conclude the protective effect of marine n-3 in Asians while suspicion exists of an aggravation of risk in Westerners, but with the possibility that it could be explained by a high heterogeneity of studies performed in this population. Some longitudinal cohorts in US/European people showed no association or a decreased risk. Further studies using more homogeneous doses, sources of n-3 and assessment of insulin sensitivity methods are required to better delineate their effects in Westerners.

Sign in / Sign up

Export Citation Format

Share Document