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We aimed to investigate the acute and chronic effects of carvedilol on insulin resistance in high-fructose, high-fat diet (HFrHFD)-fed mice and the implication of β-arrestin2 pathway. The acute effect of carvedilol (10 mg/kg, i.p.) on glucose tolerance and hepatic lipid signaling in normal and insulin resistant mice was investigated. Then, the chronic effect of carvedilol on insulin resistance and dyslipidemia in HFrHFD-fed mice was examined. Changes in β-arrestin2 and its down-stream signals in liver, skeletal muscle, and adipose tissue were measured. This involved measuring phosphatidylinositol 4,5-bisphosphate (PIP2) and diacylglycerol (DAG) levels and protein kinase B (Akt)-activity. Carvedilol acutely reduced fasting blood glucose levels in both normal and insulin resistant mice without significantly affecting the glucose tolerance. These acute effects were associated with increased hepatic PIP2 but decreased hepatic DAG levels. Chronic administration of carvedilol significantly ameliorated insulin resistance and dyslipidemia in HFrHFD-fed mice. These chronic effects were associated with increased β-arrestin2, PIP2 and Akt activity levels but decreased DAG levels in the classical insulin target tissues. In conclusion, carvedilol acutely maintains glucose homeostasis and chronically ameliorates insulin resistance and dyslipidemia in HFrHFD-fed mice. The insulin sensitizing effects of carvedilol are highly correlated with the upregulation of β-arrestin2 pathway.

Background: Sleep deprivation (SD) is a growing hazard through its effects on metabolism.Orexin is involved in regulation of both sleep and metabolism. Work on orexin receptors may explainthe mechanisms of some hazardous effects of SD. Aim:To test the role of orexin-1 receptor (OX1R)blocker, SB-334867 in changes of triglycerides and cholesterol metabolisminduced by SD. Method: 72 adult albino rats arranged in 4 equal groups: control, SD, SD-OX1R blocked &SD-DMSO groups. The 3 SD groups are subjected to 8 days of paradoxical SD using the modified multiple platform method. The OX1R blocked group was injected intraperitoneallydaily with single dose (3 mg/kg/day) of SB-334867 dissolved in 2 ml DMSOand diluted 1:1000. The SD-DMSO group was injected by 2 ml of DMSO diluted 1:1000. Triglycerides and cholesterol levels weremeasured. Results: Blood triglyceride levels dropped in all groups subjected to SD after the 1 st day while the blood cholesterol level dropped in all groups subjected to SD at the 7 th or 8 th day. In SD-OX1R blocked group showed less drop in blood triglyceridesthan the other SD groups but statistically non-significant change in cholesterol level. Conclusion: SDleads to earlier and more dropin blood triglyceridesthan the drop in cholesterol levels. This can be explained by high metabolism during SD with dependence on triglyceride more than cholesterol. OX1R blocker partially reduces the drop of triglyceride not cholesterol level indicating that orexinmay be involved in control of triglyceride metabolism but not cholesterol.

The commonest secondary cause of osteoporosis is glucocorticoid-induced osteoporosis (GIO) which is also the commonest cause of iatrogenic osteoporosis. Chronic glucocorticoids (GCs) treatment may cause fractures in 30-50% of patients. Fracture risk is increased specially among those using oral glucocorticoids. On longterm glucocorticoids therapy, deterioration of cortical bone progressively detected and long bones became increasingly fragile. Any patient with chronic glucocorticoid therapy should be suspected to suffer from GIO. Patients on glucocorticoids should receive supplementation with calcium. These deleterious influences are the result of suppression of bone formation that occurs with an early but temporal rise in the process of bone resorption. Numbers of osteoclast rapidly rise, and accompanied by inactivation of osteoblast with the decline of bone formation, these changes cause the fastest bone loss during the initial phase of the disease. Glucocorticoids cause inhibition of osteoblasts replication and function and accelerate their apoptosis. Calcium is fundamental for bone, and assuring sufficient calcium intake is important. It is said that when children and adolescents ingest large amount of calcium could result in a decrease in the danger of developing osteoporosis when they got old, however, some researches propose that solitary use of calcium supplementation might not be enough for lowering the danger for fractures. Conflicting results were reported about the effects of the use of supplemental calcium on the bone mineral content in those taking glucocorticoids therapy. Whereas, calcium supplementations were used in most bone protective treatment trials and therefore should be used as an adjunct to GIO therapy.

Background:Exercise is an effective approach for controlling DM. the exact mechanism by which exercise can control DM is still unclear. In 2012, Boström and colleagues discovered that in muscle, exercise increases the expression of FNDC5 (Fibronectin type III domain-containing protein5),amembrane protein encoded by the FNDC5 gene. The FNDC5 protein is cleaved and secreted as a new hormone called irisin suggesting that some of beneficial effects of exercise could be mediated by this hormone. The aim of the study was to estimate effect of exercise on serum irisinand fasting blood glucose levels in normal and diabetic rats. Material and methods:120 adult male albino rats were categorized them into 4 groups. Diabetes mellitus was induced by intraperitoneal injection of freshly prepared alloxan monohydrate (160mg/kg) in a single dose in Group III and Group IV Physiological saline (0.9% Nacl) was injected intraperitoneally in Group Iand Group II. Fasting blood glucose was measured weekly and two months after swimming exercise serum levels of irisin and insulin were measured. Results:Exercise increased serum levels of irisin and insulin in both control and diabetic groups alsomeasurement of blood glucose level showed that exercise had decreasing effect on blood glucose in diabetic rats. Conclusion:Swimming exercise increases serum irisinlevel also improves fasting blood glucose and insulin sensitivityin diabetic rats.

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