Anti-Inflammatory Effects of Melatonin in Rats with Induced Type 2 Diabetes Mellitus.

INTRODUCTION: Insulin resistance is associated with a pro-inflammatory state increasing the risk for complications in patients with type 2 diabetes mellitus (T2DM). In addition to its chronobiotic effects, the pineal hormone melatonin is known to exert anti-inflammatory and antioxidant effects. Melatonin was also suggested to affect insulin secretion. The aim of this study was therefore to investigate the effect of melatonin on inflammation in diabetic rats and to study the possible involvement of the melatonin receptor, MT2. MATERIALS AND METHODS: Male Sprague Dawley rats were randomly divided into four experimental groups (n = 10 per group): (1) control, (2) streptozotocin/nicotinamide induced diabetes type 2 (T2DM), (3) T2DM treated with melatonin (500 µg/kg/day), and (4) T2DM treated with melatonin (500 µg/kg/day for 6 weeks) and the selective MT2 receptor antagonist luzindole (0.25 g/kg/day for 6 weeks). Blood samples were taken for biochemical parameters and various tissue samples (liver, adipose tissue, brain) were removed for immunohistochemistry (IHC), Western blot (WB), and Q-PCR analyses, respectively. RESULTS: Melatonin significantly reduced increased blood levels of liver transaminases (AST, ALT), blood urea nitrogen (BUN), triglyceride, very low-density lipoprotein (VLDL), and cholesterol in diabetic rats with luzindole treatment partly reversing this effect regarding the lipids. Furthermore, the liver and adipose tissues of T2DM rats treated with melatonin showed lower expression of the inflammatory markers IL-1ß, IL-6, TNF-α, and NF-κB as compared to the T2DM group without melatonin. The results also showed that the MT2 receptor is at least partly involved in the protective effects of melatonin. CONCLUSIONS: Our results suggest that melatonin exerts relevant anti-inflammatory effects on various tissues in type 2 diabetic rats.

The melatonin MT2 receptor is involved in the anti-apoptotic effects of melatonin in rats with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a widely prevalent chronic disease and risk factor for several other diseases, such as cardiovascular diseases, neuropathy, nephropathy, and retinopathy. Apoptosis is a homeostatic mechanism to maintain cell numbers at a certain level in tissues. Chronic high blood glucose levels might lead to mitochondrial dysfunction and trigger undesirable apoptosis in T2DM. The pineal hormone melatonin has been shown to regulate apoptosis. The aim of this study was to investigate the impact of the melatonin MT2 receptor in the role of melatonin to prevent undesirable apotosis in different tissues of diabetic rats. Male Sprague Dawley rats were randomly divided into 4 groups; 1. Control group (only vehicle), 2. Diabetic group (streptozotozin/nicotinamide treated), 3. Diabetic group treated with melatonin (500µg/kg/day), and 4. Diabetic group treated with melatonin (500 µg/kg/day for 6 weeks) and the selective MT2 receptor antagonist luzindole (0.25 g/kg/day for 6 weeks). Various tissue samples (kidney, liver, adipose tissue, pancreas) were removed after 6 weeks for immunohistochemistry and western blot analysis. Our results demonstrated an increased rate of apoptosis in different tissues of diabetic rats compared to controls with melatonin reducing the apoptotic rate in the tissues of rats with T2DM. Furthermore, the anti-apoptotic effects of melatonin were partly mediated by the melatonin MT2 receptor.

The effects of retinoic acid on mmp-2 production, proliferation and ultrastructural morphology in rat uterus.

AIMS: Retinoic acid (RA) has a vital importance in order to ensure continuity and morphology in many tissues. Matrix metalloproteinases (MMPs) have significant roles in proliferation, the formation of cancers, and metastasis. In this study the effects of RA on MMP-2 production in cells of rat uterus were investigated. METHODS: Twenty-four adult Spraque Dawley rats were divided into two groups, the experimental group was treated with 40mg/kg/day 13-cis RA for 5days by gavage. Uterine tissue sections were treated with BrdU and MMP-2 antibodies, evaluated using light microscopy. Tissues were fixed with 2.5% glutaraldehyde and evaluated using transmission electron miroscopy. RESULTS: MMP-2 immunoreactivity decreased in the stromal cells compared with the control group and no staining of MMP-2 was observed in glandular epithelium in the experimental group. BrDU labeling of cells showed significant decrease in RA-treated group versus control group cells. Based on the electron microscopy evaluation, the surface epithelial cells of the experimental group showed vacuolization, and an accumulation of lipofuscin bodies was also observed in the gland epithelium. Cells involving autophagic vacuoles contained excess lipid granules in the entire uterus layers especially localized at the border of the endometrium and myometrium. CONCLUSION: RA had negative effects on cell proliferation and cell morphology and inhibited MMP-2 expression.

Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: a novel gene related to nuclear envelopathies.

We performed genome-wide homozygosity mapping and mapped a novel myopathic phenotype to chromosomal region 1q25 in a consanguineous family with three affected individuals manifesting proximal and distal weakness and atrophy, rigid spine and contractures of the proximal and distal interphalangeal hand joints. Additionally, cardiomyopathy and respiratory involvement were noted. DNA sequencing of torsinA-interacting protein 1 (TOR1AIP1) gene encoding lamina-associated polypeptide 1B (LAP1B), showed a homozygous c.186delG mutation that causes a frameshift resulting in a premature stop codon (p.E62fsTer25). We observed that expression of LAP1B was absent in the patient skeletal muscle fibres. Ultrastructural examination showed intact sarcomeric organization but alterations of the nuclear envelope including nuclear fragmentation, chromatin bleb formation and naked chromatin. LAP1B is a type-2 integral membrane protein localized in the inner nuclear membrane that binds to both A- and B-type lamins, and is involved in the regulation of torsinA ATPase. Interestingly, luminal domain-like LAP1 (LULL1)-an endoplasmic reticulum-localized partner of torsinA-was overexpressed in the patient's muscle in the absence of LAP1B. Therefore, the findings suggest that LAP1 and LULL1 might have a compensatory effect on each other. This study expands the spectrum of genes associated with nuclear envelopathies and highlights the critical function for LAP1B in striated muscle.