Study of plasma visfatin level in women with gestational diabetes mellitus during and after pregnancy and its relation to insulin sensitivity

The insulin-mimetic adipocytokine visfatin is highly expressed in visceral fat and whose blood levels correlate with obesity. It lowers blood glucose, improves insulin sensitivity, and recently found to act as an insulin analogue on the insulin receptors. It has been associated with insulin resistance in some studies and regulated by glucose. To evaluate the role of visfatin in GDM, typically associated with increased insulin resistance, we determined visfatin levels in women with GDM and in healthy pregnant controls. Furthermore, visfatin concentrations were investigated after delivery in a subgroup of women with GDM. 30 women with GDM [group I] and 15 age-matched healthy pregnant controls [group II] at 24-28 weeks of gestation were included in the study. All women were subjected to full history taking, complete physical examination and anthropometric measures including BMI and WHR. Venous blood samples for lipid profile, glucose, insulin and visfatin concentrations were taken 1 hour before a standard 75g OGTT and was carried out after overnight fast. Venous blood samples were repeated for glucose, insulin and visfatin 30, 60, 120 minutes after an oral glucose load. Insulin sensitivity was estimated using ISI derived from OGTT. A subgroup of 15 women with GDM [group III] was investigated for all these parameters 2 weeks after delivery. Fasting plasma visfatin concentrations were significantly higher in the gestational diabetes mellitus group during the course of pregnancy [69.04 +/- 18.41 ng/ml] than in healthy pregnant control group [31.22 +/- 24.74 ng/ml] [P<0.05]. The fasting plasma levels of visfatin showed significant drop in GDM women 2 weeks after labour [45.86 +/- 6.89 ng/ml] than during the course of pregnancy [69.04 +/- 18.41 ng/dl] [P<0.05]. The glucose-induced changes in visfatin and insulin calculated by AUC were significantly higher in GDM group during pregnancy than in healthy normal controls. The mean values of the area under the curve for glucose, insulin and visfatin curves showed significant reduction in GDM women 2 weeks after labour [P<0.05]. Significant positive correlations were detected between fasting visfatin and WHR, fasting glucose, as well as fasting insulin in GOM women during pregnancy and 2 weeks after labour. Fasting visfatin levels were negatively and significantly correlated with peripheral insulin sensitivity index in the three studied groups [P<0.05]. The precise significance of our findings indicates that adipocytokine visfatin may play a role in the pathogenesis of gestational diabetes mellitus. However, the study of the regulation of visfatin in GDM merits further considerations and further experiments are needed to clarify its role in such disease

Relation between apelin-36 and arginine vasopressin in male rats subjected to water deprivation and volume expansion

The closed anatomical localization in supraoptic and paraventricular nuclei and tissue distribution of apelin-36 and arginine vasopressin [AVP] suggest a role for the peptide apelin-36 in body fluid homeostasis and regulation of AVP release. However, conflicting reports make the precise role of apelin-36 remains to be clarified. To investigate the effect of water deprivation and acute volume expansion on plasma and brain tissue levels of apelin-36 and AVP in an attempt to clarify the interaction between the two peptides in control of body fluid homeostasis. The study was conducted on 40 male albino rats divided into 4 groups. Group I: 10 control rats, group II: 10 rats subjected to 24h-water deprivation [WD], group III: 10 rats subjected to 48h-WD and group IV: 10 rats subjected to acute volume expansion 10% of body weight by infusion of isotonic saline over 40 minutes. The following parameters were measured in all rats; plasma and brain tissue apelin -36 and AVP, plasma Na[+] and K[+] concentrations, urinary excretion rates of Na[+] and K[+] and urine flow rate per minute. Hematocrite value and plasma protein concentrations were measured to investigate the state of dehydration and hydration. Water deprivation induced significant decrease in plasma apelin-36 level associated with an increase in its brain tissue contents. This was mirrored by increased plasma AVP level and decreased brain tissue content. The reverse was detected after acute volume expansion. Moreover, increased apelin-36 concentration in plasma after acute VE was associated with diuresis and natriuresis. A significant negative correlation was detected between plasma as well as brain tissue concentrations of both apelin-36 and AVP. Apelin-36 may be implicated in the control of body fluid homeostasis and exerts opposite action to AVP in this regard. Furthermore it may be an inhibitor of AVP and the two peptides may play complementary roles in maintenance of water balance

Study of the relationship between type-1 diabetes mellitus, prolactin hormone and immune system in rats

The effects of prolactin [PRL] on lactation and reproductive organs are well known. However, its effects on other target organs and its physiological consequences remain poorly understood. Prolactin was shown earlier to act as a stimulating factor for the immune system and thus it might influence the development of autoimmune diseases, as in type-I diabetes mellitus [DM]. The aim of the present work was to clarify the role of PRL in the development of autoimmune type-1 DM aiming to answer the question of whether PRL may have a beneficial effect in type-1 DM or not. The study was conducted on sixty male albino rats matched for age and weight. Rats were divided into six groups each of ten rats; group 1: a control group [C], group 2: a vehicle-treated group [V], group 3: Streptozotocin [STZ] treated group [STZ was given intraperitoneally [i.p.] in a dose of 40 mg/kg body weight [b.w] daily for 5 consequetive days], group 4: a group of STZ + PRL [PRL was given i.p. in a dose of 4 mg/Kg b.w starting with STZ and continuing for 21 days, group 5: a group of STZ + Bromocriptine [BC], a PRL antagonist. BC was given i.p. in a dose of 10 mg/kg b.w for 21 days and group 6: a group of STZ + PRL + BC. The study showed significant elevations of serum glucose, glycosylated Hb, [HAlc], serum Interleukin-1 beta [IL-1 beta], and interferon-gamma [IFN-gamma] levels in STZ treated rats, compared to the control and vehicle treated groups. Administration of PRL with STZ induced a significant decrease in the mean values of the previous parameters compared to STZ-only treated rats, still these parameters were not close to the mean control values. BC administration with STZ and PRL prevented the induced changes found with STZ and PRL. The results of the present study indicated that PRL might affect the associated immunological changes occurring in the early phases of developing type-1 DM. The partial protective effect of PRL was suggested to be due to suppression of autoimmune mechanisms as indicated by the significant reduction of IL-1 beta and IFN-gamma in PRL + STZ treated group as compared to control mean values

Metabolic derangements of skeletal muscle by aging and zymosan-induced critical illness in rats at rest and after electrical stimulation

The present work aimed to study the metabolic derangements of skeletal muscles in critically ill rats in relation to two different physiological factors, namely, age and electrical stimulation. The study was conducted on 80 male albino rats. Two study protocols A and B, each of 40 rats, were used. Each protocol consisted of 4 groups;10 rats each. Control young group [I]: consisted of 12 months old rats [vehicle-treated], Control old group[II]: consisted of 24 months old rats [vehicle-treated], Zymosan-treated young group[III]: consisted of 12 months old rats that were given zymosan [50 mg/100g body weight] by intra peritoneal [i.p.] route and Zymosan-treated old group[IV]: consisted of 24 months old rats, that were given zymosan [50mg/100g body weight] by i.p. route. Gastrocnemius muscles were prepared and excised from rats in resting state [protocol A] or after electrical stimulation [protocol B], then quickly frozen. The measured parameters included cytochrome c oxidase activity; as a mitochondrial content index, glycogen content, adenosine triphosphate [ATP], phosphocreatine [PCr], adenosine diphosphate [ADP], creatine, pyruvate and lactate concentrations as well as pH values in skeletal muscles of all rats of the study. At rest, the aging process was associated with significant decrease in ATP, glycogen and pH in normal control rats. However, after electrical stimulation, the aged control rats had significant lower cytochrome c oxidase activity and ATP, ADP, PCr, glycogen and pH values as compared to electrically stimulated young counterparts. Zymosan injection into young rats caused significant decrease in ADP, PCr, glycogen, pyruvate and pH at rest but with additional significant decrease in cytochrome c oxidase activity and ATP levels after electrical stimulation as compared to their corresponding control groups. Generally, zymosan-treated old group had the worst metabolic derangements especially after electrical stimulation. The young-aged rats could maintain ATP levels after electrical stimulation by effective anaerobic energy-producing pathways either with apparently well-acting aerobic pathway in control rats or with partially impaired aerobic pathway in zymosan-treated rats. However, old-aged rats can't maintain ATP levels after electrical stimulation even by enhanced anaerobic pathways possibly due to improper action of oxidative pathway. Zymosan injection produced metabolic derangements in skeletal muscles of rats by causing bioenergetic alterations which was more apparent after electrical stimulation especially in old-aged group

Role of orexin-A in obesity and type 2 diabetes in male patients and its correlation with leptin hormone

To study role of orexin-A in obesity, type 2 diabetes as well as combined obesity and type2 diabetes in male patients and its correlation with leptin hormone. The study was conducted on 30 male patients and 10 healthy age and sex matched control subjects. The patients were divided into 3 groups each of ten as follow: obese normoglycemic, nonobese type 2 diabetic and obese type 2 diabetic patients. All patients and controls were subjected to full history taking and complete clinical examination with determination of BMI. The following parameters were measured: fasting serum levels of glucose, insulin, triglycerides and glycosylated hemoglobin. Serum orexin-A and leptin concentrations were determined. The results of the study revealed that, serum orexin-A was significantly low in all the studied patient groups as compared to control subjects. Significant high serum leptin levels were detected in all patient groups compared to normal ones. An inverse correlation was found between serum orexin-A and BMJ, leptin, glucose and insulin levels. On the other hand, serum leptin was positively correlated with BMI and insulin levels. Orexin-A is implicated in the pathogenesis of both obesity and type 2 diabetes. Leptin may be an important negative regulator of orexin-A

Effect of folic acid and vitamin B[12] supplementation on isoprenaline induced myocardial infarction, endothelial dysfunction and atherothrombosis in experimental hyperhomocysteinemic rats

Elevated total plasma homocysteine [tHcy] concentration is an independent risk factor for ischemic heart disease and other vascular disorders. Treatment with vitamins [folic acid and B12] has shown to reduce plasma homocysteine level but it is not clear to what extent such treatment may reduce clinical vascular events or mortality. The aim of the present study was to evaluate hyperhomocysteinemia as a risk factor of isoprenaline induced myocardial infarction [MI], endothelial dysfunction and hypercoagulable state and to examine the effect of folic acid either alone or in combination with vitamin B[12] on the experimentally induced myocardial infarction and to evaluate the effect of such vitamin treatment on the biomarkers of endothelial dysfunction and hypercoagulable state in post-methionine load hyperhomocysteinemic rats. Hyperhomocysteinemia [Hhcy] was induced in rats by daily intake of methionine [1g/kg b.wt.] in the drinking water for 4 weeks. MI was then induced by subcutaneous injection of isoprenaline in a dose of 85mg/kg b.wt/day for two days. Serum marker enzymes, creatine kinase [CK] and lactate dehydrogenase [LDH] were measured. Lipid peroxidation was measured as malondialdehyde [MDA] and reduced glutathione [GSH] concentrations in heart tissue. Plasma concentrations of von Willebrand factor [vWF] and D-dimer as markers of endothelial dysfunction and prothrombotic state were measured either in the experimental untreated hyperhomocysteinemic rats or in the treated ones. Hhcy resulted in a significant increase in serum CK and LDH levels. Cardiac MDA was significantly increased while GSH was significantly decreased in Hhcy group compared to the normal control group, plasma concentrations of vWF and D-dimer were also significantly increased. Serum marker enzymes and markers of cardiac oxidative stress were greatly exaggerated in Hhcy rats treated with isoprenaline in comparison with isoprenaline group. Administration of folic acid [10mg/kg, b.wt orally via gavage] alone and in combination with vitamin B[12] [500 ug/kg b.wt. i.m], concurrently for 4 weeks during the induction of Hhcy markedly reduced the increase in serum CK and LDH as well as the plasma concentration of vWF and D-dimer. Cardiac MDA content was decreased while cardiac GSH was elevated in the treated group compared to untreated Hhcy rats. These results suggest that Hhcy aggravates MI via oxidative stress mechanisms and that Hhcy may impair endothelial function and increases the biomarkers of prothrombotic state Treatment with either folic acid alone or in combination with vitamin B[12] can ameliorate the detrimental effects of Hhcy, reduce the risk of MI, appears to improve endothelial dysfunction and decrease plasma concentration of biomarkers of hypercoagulability. This provides preliminary evidence that such vitamin supplementation may have beneficial cardiovascular effects. However clinical benefit of vitamin supplementation has not yet been demonstrated and clinical trials are urgently required