ABSTRACT
Aim To study the effect of melatonin receptor agonist Neu-pl 1 on IR in T2DM rats and to predict its possible mechanism. Methods Long-term high-fat feeding plus low-dose streptozotocin (STZ, 30 mg • kg"1, IP) were used to induce an animal model of type 2 diabetes in female rats. After 4 weeks of intragastric administration, liver tissue was sacrificed. Hie mRNA expression levels of Sirtl, Nrf-1/2 and ERRa in rats were determined by RT-PCR. The relative expressions of PGC-la and Mfn2 were determined by Western blot. Rat INS was measured and HOME-IR and ISI were calculated. The liver ATP content and ATPase activity were measured. Results Compared with normal group, T2DM rats developed IR, PGC-la, Mfn2 protein expression increased, Sirtl and other mRNA expression decreased significantly, ERRa mRNA expression increased, ATP content decreased significantly, and ATPase activity decreased. Compared with model group, the Neu-pll low-dose group reduced INS in T2DM rats, improved IR in T2DM rats, up-regulated rat liver protein and mRNA expression, down-regulated ERRa mRNA expression, and increased rat liver ATP content and ATPase activity. Conclusions The melatonin receptor agonist Neu-pl 1 may improve IR by regulating the mitochondrial bal-ance-related factors in liver of T2DM rats and maintaining normal mitochondrial function.
ABSTRACT
<p><b>BACKGROUND</b>People with metabolic syndrome are at higher risk for developing coronary artery disease (CAD). The effect of the metabolic syndrome on outcomes in patients with preexisting CAD has not been well studied. This study was conducted to assess the prevalence, characteristics, in hospital and long term prognosis of CAD with metabolic syndrome and to determine the factors influencing the prognosis of the disease.</p><p><b>METHODS</b>The DESIRE registry contains data of 3696 patients with CAD between 2001 and 2004. Mean long term followup was (829 +/- 373) days. Diagnosis of metabolic syndrome was based on modified International Diabetes Federation (IDF) Worldwide Definition of the Metabolic Syndrome, using body mass index (BMI) instead of waist circumference.</p><p><b>RESULTS</b>Of 2596 patients with complete records of height, weight, and so on, 1280 (49.3%) were identified with metabolic syndrome. The patients with metabolic syndrome had higher level of body mass index, systolic blood pressure, diastolic blood pressure, fasting glucose and disordered blood lipid (all P < 0.0001), with higher creatinine [(10.5 +/- 4.3) mg/L vs (9.9 +/- 2.9) mg/L, P < 0.0001] and the number of white blood cells [(7.49 +/- 2.86) x 10(9)/L vs (7.19 +/- 2.62) x 10(9)/L, P = 0.008) compared with those without metabolic syndrome. The patients with metabolic syndrome showed severer coronary angiographic alterations (left main artery and/or > or = 2-vessel) (73.6% vs 69.6%, P = 0.031). There were no significant differences of major adverse cardiac and cerebral events (MACCE) or mortality in hospital between the two groups. During followup, the ratio of MACCE in CAD with metabolic syndrome patients increased significantly (11.8% vs 10.0%, P = 0.044). Fasting blood glucose (> or = 1000 mg/L) and triglyceride (TG, > or = 1500 mg/L) were responsible for most of the increased risk associated with the metabolic syndrome (adjusted OR 1.465, 95% CI 1.037 - 1.874, P = 0.032; OR 1.378, 95% CI 1.014 - 1.768, P = 0.044).</p><p><b>CONCLUSIONS</b>The prevalence of metabolic syndrome was very high in CAD patients. The metabolic syndrome confers a higher risk of long term MACCE in patients with CAD, and dysglycaemia and hypertriglycaemia appear to be responsible for most of the associated risk.</p>