Fasting Serum Insulin Levels Research Articles

Milk fat globule membrane and its component phosphatidylcholine induce adipose browning both in vivo and in vitro

The functional induction of brown-like adipocytes in white adipose tissue (WAT) provides a defense against obesity. The aim of this study was to analyze the effects of milk fat globule membrane (MFGM) and its component phosphatidylcholine (PC) on the brown remodeling of WAT. Male C57BL/6 J mice were fed a high-fat diet (HFD) for 8 weeks and then fed HFD for another 8 weeks with MFGM. In vitro studies were performed in C3H10T1/2 pluripotent stem cells, 3T3-L1 pre-adipocytes and differentiated inguinal WAT stromal vascular cells (SVCs) to determine the role of MFGM and PC on the formation of brown-like adipocytes. MFGM decreased fasting glucose and serum insulin levels in HFD-fed mice. MFGM improved glucose tolerance and insulin sensitivity, and induced browning of inguinal WAT. MFGM and its component PC stimulated transformation of brown-like adipocytes in C3H10T1/2 pluripotent stem cells, 3T3-L1 adipocytes and SVCs by increasing the protein expression of UCP1, PGC-1α, PRDM16 as well as the mRNA expression of other thermogenic genes and beige cell markers. MFGM and PC also increased mitochondrial DNA (mtDNA) copy number, mitochondrial density and oxygen consumption rate and up-regulated the mRNA expression of mitochondria-biogenesis-related genes in vitro. PPARα inhibitor GW6471 treatment or knockdown of PPARα using lentivirus-expressing shRNA inhibited the PC-induced increase in the protein expression of UCP1, PGC-1α and PRDM16 in C3H10T1/2 pluripotent stem cells and 3T3-L1 adipocytes, indicating the potential role of PPARα in PC-mediated brown-like adipocyte formation. In conclusion, MFGM and milk PC induced adipose browning, which has major protective effects against obesity and metabolic dysfunction.

Serum Triglycerides and Total Cholesterol levels and its Relation with type 2 148 Diabetes mellitus

Diabetes mellitus is one of the most widespread endocrine disorder in female and its complications are increasing all over the world, leading to life threatening medical problems like cardiovascular diseases, stroke and end stage renal diseases. A relation between hyperlipidemia and diabetes mellitus has been identified. The study was carried out to observe the serum triglycerides and total cholesterol levels its relation with type 2 diabetes mellitus in adult female subjects. This cross sectional study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka, during the period of January 2011 to December 2011. A total number of sixty female subjects were selected with age ranging from30 to50 years. Among them 30 female subjects with diabetes were included from out-patient department of Endocrinology, Dhaka Medical College Hospital, Dhaka as study group(B) and 30 apparently healthy female were taken as control group(A) for comparison. Estimation of fasting serum triglycerides (TG) and total cholesterol (TC) levels were done by enzymatic method in the Department of Physiology, Dhaka Medical College Dhaka in both groups. Fasting serum insulin level was measured by ELISA method in the Department of Laboratory of National Institute of ENT, Dhaka and fasting blood glucose was estimated by glucose oxidase method in Department of Dhaka Medical College in both groups. Data were analyzed by Unpaired Student’s- test and Pearson’s correlation co-efficient (r) test as applicable. The value of fasting serum TG and TC level were significantly higher in study subjects than those of control. In study subjects fasting serum TG and fasting serum TC levels showed positive correlation with fasting blood glucose and serum insulin level.
 Conclusion: Present study revealed that fasting serum triglyceride (TG) and fasting serum cholesterol (TC) levels have positive relationship with fasting serum insulin and fasting blood glucose levels.
 J Dhaka Medical College, Vol. 27, No.2, October, 2018, Page 148-154

Circulating Follistatin and Activin A and Their Regulation by Insulin in Obesity and Type 2 Diabetes

Circulating follistatin (Fst) binds activin A and thereby regulates biological functions such as muscle growth and β-cell survival. However, Fst and activin A's implication in metabolic regulation is unclear. To investigate circulating Fst and activin A in obesity and type 2 diabetes (T2D) and determine their association with metabolic parameters. Further, to examine regulation of Fst and activin A by insulin and the influence of obesity and T2D hereon. Plasma Fst and activin A levels were analyzed in obese T2D patients (N = 10) closely matched to glucose-tolerant lean (N = 12) and obese (N = 10) individuals in the fasted state and following a 4-h hyperinsulinemic-euglycemic clamp (40 mU·m-2·min-1) combined with indirect calorimetry. Circulating Fst was ~30% higher in patients with T2D compared with both lean and obese nondiabetic individuals (P < .001), while plasma activin A was unaltered. In the total cohort, fasting plasma Fst correlated positively with fasting plasma glucose, serum insulin and C-peptide levels, homeostasis model assessment of insulin resistance, and hepatic and adipose tissue insulin resistance after adjusting for age, gender and group (all r > 0.47; P < .05). However, in the individual groups these correlations only achieved significance in patients with T2D (not plasma glucose). Acute hyperinsulinemia at euglycemia reduced circulating Fst by ~30% (P < .001) and this response was intact in patients with T2D. Insulin inhibited FST expression in human hepatocytes after 2 h and even further after 48 h. Elevated circulating Fst, but not activin A, is strongly associated with measures of insulin resistance in patients with T2D. However, the ability of insulin to suppress circulating Fst is preserved in T2D.

Pengaruh yoghurt dan soyghurt kayu manis (Cinnamomum burmannii) terhadap kadar glukosa darah, insulin serum, dan malondialdehyde tikus pra sindrom metabolik

Background: Pre metabolic syndrome is characterized by two of five risk factors: central obesity, dyslipidemia, hypertension, and increased fasting blood glucose. Cinnamon yogurt and soygurt contain antioxidants and fiber which can improve insulin sensitivity and blood glucose homeostasis and prevent cell damage in pre-metabolic syndrome conditionsObjective: This study aimed to determine the effect of cinnamon yogurt and soygurt on fasting blood glucose (FBG), serum insulin, and malondialdehyde (MDA) levels in pre-metabolic syndrome rats.Method: This study was an experimental study with a pre and post-test control group design. The subjects were 15 male Sprague Dawley rats which were divided into 5 normal control mice (K) and 10 pre metabolic syndrome mice with a diet high in fat and fructose for group P1 (yogurt) and P2 (soygurt) each of 5 mice. The yogurt and soygurt were given as much as 3.4 ml / g BW for 28 days. FBG levels were measured by the GOD-PAP method, while serum insulin and MDA levels were by the ELISA method. Different tests before and after treatment using Paired t-test or Wilcoxon. The difference tests between groups using the One-Way ANOVA test or Kruskal Wallis.Results: There were no differences in FBG and MDA levels between groups after intervention (p&gt; 0.05). The highest percentage reduction in FBG in the P2 (-11.59%), then P1 (-4.06%). The decrease in MDA levels in group P1 = 19.17%, and P2 = 15.44% lower than K = 24.43%. After the intervention, the insulin level in group P2 (0.46 ng / ml) was significantly higher than P1 (0.318 ng/ml), but both were not different from K (0.384 ng / ml).Conclusion: There was no significant effect on the administration of cinnamon yogurt and soygurt to FBG, serum insulin, and MDA levels.

Serum Galectin-3 and its Relation to Insulin Resistance in Patients with Acne Vulgaris

Acne vulgaris is one of the most prevalent inflammatory skin diseases. It is particularly prevalent during the late adolescent period. It is a chronic skin disease of the pilosebaceous unit and develops due to blockages in the skin's hair follicles. to evaluate serum galectin-3, fasting insulin and fasting blood glucose levels in patients with AV, assessment of its clinical significance, relation to severity of AV and its relation to Insulin resistance (IR). This study included 60 patients suffering from AV. In addition to 20 apparently healthy individuals of matched age and sex as a control group. All studied individuals were subjected to complete history taking and complete clinical examination. there was a statistically significant difference regarding the serum galectin-3and HOMA-IR values between studied patients and control groups. HOMA-IR levels were higher in patients than controls, which indicate presence of IR in AV patients more than the controls. Besides, HOMA-IR levels were higher in severe AV than mild or moderate AV. Regarding serum galectin-3 level; it was significantly higher in AV patients than controls. IR is more common among AV patients especially in patients with severe AV lesions and that could be explained by higher serum galectin-3 level in those patients. Since acne is a problem in adolescents, the early recognition of IR might help in better management of acne patients.

Serum insulin levels are associated with vulnerable plaque components in the carotid artery: the Rotterdam Study.

BackgroundTo investigate the association between fasting serum insulin and glucose levels with atherosclerotic plaque composition in the carotid artery. Impaired insulin and glucose levels are implicated in the etiology of cardiovascular disease; however, their influence on the formation and composition of atherosclerotic plaque remains unclear.MethodsIn 1740 participants (mean age 72.9 years, 46% women, 14.4% diabetes mellitus) from the population-based Rotterdam Study, we performed carotid MRI to evaluate the presence of calcification, lipid core, and intraplaque hemorrhage in carotid atherosclerosis. All participants also underwent blood sampling to obtain information on serum insulin and glucose levels. Using logistic regression models, we assessed the association of serum insulin and glucose levels (per s.d. and in tertiles) with the different plaque components, while adjusting for sex, age, intima-media thickness, and cardiovascular risk factors.ResultsSerum insulin levels were associated with the presence of intraplaque hemorrhage (adjusted odds ratio (OR): 1.42 (95% CI: 1.12–1.7)) We found no association with the presence of calcification or lipid core. Sensitivity analyses restricted to individuals without diabetes mellitus yielded similar results. No associations were found between serum glucose levels and any of the plaque components.ConclusionsSerum insulin levels are associated with the presence of vulnerable components of carotid plaque, specifically with intraplaque hemorrhage. These findings suggest a complex role for serum insulin in the pathophysiology of carotid atherosclerosis and in plaque vulnerability.

A comparison between whole mung bean and decorticated mung bean: beneficial effects on the regulation of serum glucose and lipid disorders and the gut microbiota in high-fat diet and streptozotocin-induced prediabetic mice.

The aim of this study is to investigate the beneficial effects of whole mung bean (WMB) and decorticated mung bean (DMB) on the regulation of serum glucose and lipid disorders in high-fat diet (HFD) and streptozotocin (STZ)-induced prediabetic mice, and to further explore their gut microbiota modulatory effects. In the present study, the ability of mung bean-based diets to combat prediabetes-related metabolic disorders was determined by assessing the changes in the physiological, biochemical, and histological parameters, and the gut microbiota composition of prediabetic mice. The supplementation of both WMB and DMB can effectively alleviate HFD and STZ-induced impaired glucose tolerance (P < 0.05), which was accompanied by improvements in pancreatic β-cell damage and hepatic steatosis. However, only WMB supplementation significantly decreased the fasting blood glucose and fasting serum insulin levels by sensitizing insulin action (P < 0.05), and reduced the serum lipid profiles and glycosylated serum protein levels (P < 0.05). Furthermore, high-throughput pyrosequencing of the 16S rRNA gene revealed that WMB and DMB supplementation could prevent HFD and STZ-induced gut microbiota dysbiosis, especially for the enrichment of some benign bacteria, such as Bifidobacterium and Akkermansia, and the reduction of some harmful bacteria (Staphylococcus and Enterococcus). Overall, although decortication processing had an impact on the beneficial effects of mung bean, it did not cause the loss of all health benefits.

A study of clinical and investigational profile of hirsute women at a tertiary care center in Western India

Background: Hirsutism is defined as a male pattern of hair distribution in a female. The interplay of androgens as well as other non androgenic hormones has an important role in the causation of hirsutism. Objectives: The objective of this study was to investigate the prevalent causes for hirsutism and to study the clinical profile of patients presenting with hirsutism. Methodology: Patients who came with features of hirsutism were screened by the modified Ferriman–Gallwey (mFG) scale and those with mFG ≥8 were included in the study. Patient's clinical history, family history, body mass index, general examination, dermatological examination, and systemic examination were carried out. Serum total testosterone, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH: FSH ratio, dehydroepiandrosterone sulfate (DHEAS), thyroid-stimulating hormone, blood sugar levels (fasting and postprandial), and abdomino-pelvic ultrasound were performed for all patients. Serum prolactin, free testosterone, 17 hydroxyprogesterone, T3level, T4level, serum cortisol level, and serum fasting insulin levels were performed in selected patients depending on the clinical scenario. Results: A total of 44 patients were studied during the study. About 95.45% of patients were categorized under mild mFG, whereas 4.55% of patients had moderate mFG score. Idiopathic hirsutism (IH) was the most common cause in our patients which accounted for 43.18% of patients followed by polycystic ovarian syndrome (PCOS) which was the reason for hirsutism in 38.64% of patients. Total testosterone was raised in 25% of patients. Free testosterone levels were performed for 25 patients and found to be raised in six patients. Five patients had elevated DHEAS levels of which four had PCOS and one had late-onset congenital adrenal hyperplasia. Conclusion: IH was the most common cause of hirsutism in our patients which was followed by PCOS.

Polysaccharide from Rosa roxburghii Tratt Fruit Attenuates Hyperglycemia and Hyperlipidemia and Regulates Colon Microbiota in Diabetic db/db Mice.

This study was aimed at investigating the hypoglycemic and hypolipidemic effects of a polysaccharide (RTFP) isolated from Rosa roxburghii Tratt fruit on type-2 diabetic db/db mice. The results indicated that the oral administration of RTFP could significantly decrease the body weight, fat, and liver hypertrophy and the levels of fasting blood glucose, serum insulin, and serum lipids of the db/db mice. Histopathological observation showed that RTFP could effectively protect the pancreas, liver, and epididymal fat against damage and dysfunction. Real-time quantitative polymerase chain reaction analysis confirmed that the gene expression levels of peroxisome proliferator-activated receptors-γ (PPAR-γ), sterol regulatory element-binding protein-1 (SREBP-1c), acetyl-CoA carboxylase-1 (ACC-1), fatty acid synthase (FAS), and glucose-6-phosphatase (G6 Pase) were significantly down-regulated in the liver of db/db mice after treatment with RTFP. Moreover, RTFP treatment reversed gut dysbiosis by lowering the Firmicutes-to-Bacteroidetes ratio and enhancing the relative abundances of beneficial bacteria including Bacteroidaceae, Bacteroidaceae S24-7 group, and Lactobacillaceae. These findings suggest that RTFP can be used as a promising functional supplement for the prevention and treatment of type-2 diabetes mellitus.

Clinical characteristics of insulin resistance syndromes: A nationwide survey in Japan.

Aims/IntroductionInsulin resistance syndrome (IRS) of type A or B is triggered by gene abnormalities of or autoantibodies to the insulin receptor, respectively. Rabson–Mendenhall/Donohue syndrome is also caused by defects of the insulin receptor gene (INSR), but is more serious than type A IRS. Here, we carried out a nationwide survey of these syndromes in Japan.Materials and MethodsWe sent questionnaires to a total of 1,957 academic councilors or responsible individuals at certified facilities of the Japan Diabetes Society, as well as at the department pediatrics or neonatology in medical centers with >300 beds.ResultsWe received 904 responses with information on 23, 30 and 10 cases of type A or B IRS and Rabson–Mendenhall/Donohue syndrome, respectively. Eight cases with type A IRS‐like clinical features, but without an abnormality of INSR, were tentatively designated type X IRS, with five of these cases testing positive for PIK3R1 mutations. Fasting serum insulin levels at diagnosis (mean ± standard deviation) were 132.0 ± 112.4, 1122.1 ± 3292.5, 2895.5 ± 3181.5 and 145.0 ± 141.4 μU/mL for type A IRS, type B IRS, Rabson–Mendenhall/Donohue syndrome and type X IRS, respectively. Type A and type X IRS, as well as Rabson–Mendenhall/Donohue syndrome were associated with low birthweight. Type B IRS was diagnosed most frequently in older individuals, and was often associated with concurrent autoimmune conditions and hypoglycemia.ConclusionsInformation yielded by this first nationwide survey should provide epidemiological insight into these rare conditions and inform better healthcare for affected patients.

PSIV-B-34 Late-Breaking: Targeted metabolomics analysis reveals that dietary super-nutritional selenium regulates energy metabolism homeostasis in pig liver

Abstract Energy metabolism is a major mechanism of power reduction needed to maintain the redox state in an organism. By using a selenium (Se)-deficiency model we have previously demonstrated that Se can shift glycolysis by regulating the redox state in pig skeletal muscle. How dietary super-nutritional Se affects the energy metabolism in pig liver remains unknown. In the present study, super-nutritional Se supplementation (as selenomethionine) effects on liver selenoprotein expression and energy metabolite profiles in pigs were evaluated. In total, 36 castrated male pigs (Duroc × Landrace × Yorkshire, 62.3 ± 3.3 kg) were randomly assigned to two treatment groups with six replicates of three pigs per replicate. The two treatment groups received the same basal diet supplemented with different levels of selenomethionine: Se adequate (Se-A, 0.25 mg Se/kg) and Se supra-nutritional (2.5 mg Se/kg) for 60 days. Animals were then scarified and their livers were sampled for Se content, selenotranscriptome, and energy-targeted metabolite profile analysis. Super-nutritional Se supplementation increased the levels of serum fasting glucose, insulin, and free fatty acid levels (P &amp;lt; 0.05), as well as elevated the total Se liver content (P &amp;lt; 0.05). Glutathione peroxidase 4 mRNA expression was upregulated, while thioredoxin reductase 1 and selenoprotein W mRNA expression levels were downregulated in the super-nutritional Se group. LC-MS-based target metabolomics showed that high Se supplementation increased the levels of most metabolites involved in glycolysis, pentose phosphate pathway, tricarboxylic acid cycle, and acylcarnitine metabolism. These results indicated that dietary super-nutritional Se can regulate energy metabolism homeostasis in the pig liver.

The Relationship of Angiotensin I-Converting Enzyme Genotype to Liver Fibrogenesis in Non-Alcoholic Steatohepatitis

AbstractBackground: Multiple genetic and environmental factors may lead to fibrogenesis in patients with Non-alcoholic fatty liver (NAFL). Many studies investigated the relation of angiotensin I-converting enzyme (ACE) genotyping to liver fibrosis in chronic liver disease; and the results are contradic-tory.Aim of Study: In the current study, ACE genotype was assessed in NAFLD patients to show its possible association with development liver fibrosis.Subjects and Methods: The study included 162 patients of NAFLD disease, 49 (30.25%) patients with mild fibrosis, 65 (40.12%) with moderate fibrosis and 48 (29.63%) with severe fibrosis in addition to 138 volunteers was enrolled as a healthy controls. All patients and controls were investigated to serum glucose and fasting insulin level and HOMA-IR was calculated. Liver function tests, both serum ACE and trans-forming growth factor-beta (TGF-b) were done. ACE geno-typing [insertion/deletion (I/D)] was done by PCR.Results: Fasting glucose and insulin, HOMA-IR, AST, ALT and GGT were significantly higher in NAFLD patients than healthy controls. The homozygous frequency I/I and D/D or D/I of ACE were not significantly different between NAFLD patients and controls. The D/D genotype was associated significantly with the severity of liver fibrosis, D/I polymor-phism with moderate fibrosis and I/I genotype with mild fibrosis. The higher D allele frequency was associated with severe fibrosis, while I allele was frequent in mild fibrosis. The HOMA-IR, ALT, serum ACE and TGF-b were increased significantly in the patients carrying D/D homozygous gene more than those carrying homozygous I/I or D/I polymorphism. The serum ACE and TGF-b were significantly higher in NAFLD patients compared to control and the most higher levels was reported in cases with severe liver fibrosis than moderate and mild liver fibrosis.Conclusion: ACE (D/D) genotype was closely associated with liver fibrosis severity and ACE (I/D) polymorphism was observed in moderate stage of fibrosis. The allele D is seems to be a risk factor for liver fibrosis development than allele I. The knowledge of the ACE genotypes in NAFLD patients may be important for treatment decision in those patients and beneficial in the follow-up of the disease progression.

PREVALENCE OF NAFLD AND IT’S ASSOCIATION WITH INSULIN RESISTANCE IN PATIENTS WITH DIABETES

Objectives: Non Alcoholic Fatty Liver Disease (NAFLD) is characterized by fatty infiltration of the liver, mostly in the form of triglycerides (TG), which exceeds 5% of the liver weight.NAFLD is strongly associated with Insulin Resistance(IR).Patients with NAFLD also having type 2 diabetes carry added risk of progressive forms of the disease particularly cirrhosis. They also have poor glycemic control owing to IR. So it is logical to identifying the patients with diabetes having NAFLD could estimates the future risk and help in prevention of chronic liver disease and delaying the progression to NASH and cirrhosis and various complications of Diabetes.&#x0D; Methods: This was a cross sectional observational study conducted in department of medicine, N.S.C.B., MCH, Jabalpur in which 100 cases of diabetes were taken who satisfied inclusion and exclusion criteria. Abdominal USG was used for evidence of fatty liver and it’s grading and fasting serum levels of insulin (FIL) and fasting blood sugar(FBS) were used to calculate HOMA IR value to find presence of IR.&#x0D; Results: Our study showed prevalence of NAFLD was 56%(n-56),Among these,in 58.92%(n-33) cases NAFLD is associated with IR(chi square value-4.1,p value-0.041).Prevalence of NAFLD was slightly more in females-56.6%(n-30) as compare to males-55.32%(n-26).Strong association of NAFLD with IR is found among females as compare to males (p-0.022 and p-0.79 respectively). Waist circumference, Mean BMI, FBS, Triglycerides, FIL and HOMA IR levels in cases with NAFLD (95.11±12.46, 24.83±2.42, 176.13±66.79, 180.07±51.35, 13.59±15.42, 5.33±5.21)were higher as compare to non NAFLD (85.84±9.86, 22.41±2.16, , 134.8±34.41,139.09±39.27, 6.79±4.49, 2.37±1.94)respectively. The mean AST and ALT levels were higher in NAFLD group than Non NAFLD group (t= 2.23,2.19) respectively with p value &lt;0.05.Prevalence of NAFLD was 88.23%(n-15)in obese population.&#x0D; Conclusion: Given the high prevalence of NAFLD in patients with diabetes, the possibility of NAFLD should be suspected in all of them. These patients with NAFLD have high propensity of IR than Non NAFLD patients, so are at higher risk of developing complications of diabetes, NASH and cirrhosis. Also obese diabetic patients have higher incidence of NAFLD and IR as compared to non-obese patients. It seems reasonable to expect that early diagnosis of NAFLD and early intervention with strict glycemic control and weight loss would prevent complications.

Tetramethylpyrazine alleviates diabetic nephropathy through the activation of Akt signalling pathway in rats

In the whole world, the principal cause of end-stage renal disease is diabetic nephropathy (DN), which is one of the most relentless complications of diabetes. However, there is a shortfall of compelling DN treatments and the mechanism potentially able to alleviate renal injury remains ambiguous. In this experiment, we estimated the preventive actions of tetramethylpyrazine (TMP) on DN in rats and further investigated the underlying mechanism. The different doses of TMP (100 mg/kg, 150 mg/kg and 200 mg/kg) were orally given each day for 8 weeks in streptozotocin (STZ) - nicotinamide (NCT) - induced type-2 diabetic (T2D) rats. The metabolic parameters of diabetes, blood urea nitrogen (BUN), serum creatinine (SCR), urinary protein and oxidative stress parameters were assessed. Microstructural changes in kidney were observed, and the expression of Akt signalling pathway proteins was measured by western blotting. TMP administration in T2D rats improved diabetic condition, as demonstrated by significant (P < 0.05) increase of body weight and fasting serum insulin (FSI) level, reduction of fasting blood glucose (FBG) and glycosylated haemoglobin (HbA1c) level and regulation of lipid profile and oral glucose tolerance in a dose-dependent manner. TMP treatment also reduced BUN, SCR, urinary protein and oxidative stress and prevented renal injury in diabetic rats. TMP activated Akt signalling pathway, increased the levels of p-Akt and Bcl-2, and diminished the expressions of p-GSK-3β, Bax and cleaved caspase-3. In conclusion, TMP ameliorates diabetic nephropathy in T2D rats by initiating the Akt signalling, improving the metabolic markers of diabetes and suppressing oxidative stress.

Early intervention with breast milk mesenchymal stem cells attenuates the development of diabetic-induced testicular dysfunction via hypothalamic Kisspeptin/Kiss1r-GnRH/GnIH system in male rats

Diabetic male infertility and sub fertility are major complications that may implicate both central and peripheral pathways as well as mechanisms controlling reproduction. This study was an attempt to explore the potential effect of breast milk mesenchymal stem cells (Br-MSCs) as a therapeutic tool for diabetic induced reproductive dysfunction at molecular level. Forty-five adult male Sprague Dawely rats were divided into 3 groups (n = 15); control group, diabetic group, and Br-MSCs treated diabetic group. The homing ability of Br-MSCs in diabetic treated rat testicles was confirmed via semi-quantitative RT- PCR analysis of a human specific Gapdh mRNA expression level. Our result showed that type1 diabetic rats exerted an elevation in blood glucose level and a reduction in body weight, fasting serum insulin, FSH, LH, and total testosterone levels, relative and absolute testicular weights, sperm count, motility, and live ratio. In addition, downregulation in the hypothalamic kisspeptin-GnRH system, HPG axis and testicular steroidogenesis compared to control group was noticed. Moreover, upregulation of testicular proinflammatory and apoptotic markers relative mRNA expression compared to control group was observed. Furthermore, a decrease in testicular tissue antioxidant activity (CAT, SOD, GSH) and an increase in lipid peroxidation (MDA) compared to control group was shown. However, Br-MSCs administration restored or even exceeded the normal physiological tone in most of these parameters to the point where a potential therapeutic role for Br-MSCs in type1diabetic induced infertility can be suggested.

Rate of Metabolic Syndrome Among Patients with Facial Acanthosis Nigricans

Facial acanthosis nigricans (FAN) is an ignored dermatological entity. Nowadays it occurs more frequently than previous days may be due to changing economic and social status of our country. Aim of this study was to assess the rate of metabolic syndrome in cases of facial acanthosis nigricans. This observational study was conducted in the outpatient department (OPD) of dermatology and Venereology of Bangabandhu Sheikh Mujib Medical University (BSMMU) in the year 2017 among thirty clinically diagnosed cases of FAN. After taking their informed written consent; BMI, random plasma glucose, fasting lipid profile and serum insulin level was estimated in venous blood and recorded accordingly. To confirm metabolic syndrome we followed NCEP ATP III guideline (2005) where 3 of 5 positive criteria confirmed the diagnosis. All data was preserved in a secured computer device and was analyzed with SPSS program with appropriate statistical tools. Mean (±SD) age of patients was 35.63 ± 14.26 years and male to female ratio was 1:1.14. The mean BMI of cases was 33.73±3. We found 11 cases with hypertension, 8 with type II diabetes mellitus and 9 with dyslipidemia. Among the 30 cases of FAN 12 zygomatic type, 8 generalized type and 5 had band like pigmentation on the forehead. Twenty-three patients had acanthosis nigricans on both sides of body. According to our preset criteria we found 26.66% cases had metabolic syndrome. The rate of metabolic syndrome is higher in facial acanthosis nigricans patients. A further large scale study is recommended for strengthening this study findings.&#x0D; Bangladesh Med J. 2018 May; 47 (2): 12-16

P737Endothelial ERK2/thromboxane receptor pathway induces endothelial dysfunction, insulin resistance and steatohepatosis through superoxide with high fat high sucrose diet

Abstract Introduction Metabolic syndrome (MetS) is well known as the risk of cardiovascular diseases associated with endothelial dysfunction and induces steatohepatosis. Insulin resistance is a major character of MetS, which affects intracellular signaling pathways and endothelial function. Extracellular signal-regulated kinase (ERK) is a major component of insulin signal and many of vasoactive peptides, which were released in MetS, can activate it in endothelium. However, the role of endothelial ERK in nitric oxide (NO) bioactivity in MetS in in vivo has been unknown. Purpose The aim of this study is to clarify the role of endothelial ERK2 on NO bioactivity in mice model of MetS. Methods and results We created endothelial specific ERK2 knock out mice (EE2KO) crossing Tie2-Cre mice and ERK2 flox mice and fed them with normal or high-fat/high-sucrose diet (HFHSD) for 24 weeks. Serum glucose and insulin levels and HOMA-IR were lowered in EE2KO with HFHSD without changing body weight. In wild type mice (WT) with HFHSD, nonalcoholic fatty liver disease (NAFLD) activity score, fibrosis score and serum ALT level were increased, all of which were blunted in EE2KO. EE2KO with HFHSD lowered systolic blood pressure (WT: 123.7±5.83 mmHg, EE2KO: 101.4±3.66 mmHg, P&lt;0.01, N=8) without changing heart rate, which was increased to the same levels with L-NAME, an endothelial NO synthase inhibitor, in both groups. Serum NO levels measured with serum nitrite/nitrate concentrations were increased in EE2KO with HFHSD (WT: 23.10±3.74 μmol/l, EE2KO: 41.71±6.73 μmol/l, P&lt;0.05, N=12). Endothelial function was assessed with the isometric tension measurement of aortic rings with acetylcholine (ACh). ACh-induced relaxation was improved in EE2KO with HFHSD. Superoxide production of aorta from EE2KO was lowered than WT with HFHSD in dihydroethidium (DHE) staining. S18886, an antagonist of the thromboxane A2-prostanoid (TP) receptor, decreased superoxide production of aorta in DHE staining resulting in improving endothelial function in the isometric tension measurement of aortic rings. Oral administrations of S18886 decreased systolic blood pressure, serum fasting glucose and insulin levels, and surprisingly improved steatohepatosis by decreasing NAFLD activity score and fibrosis score. Relaxation of aortic rings with ACh Conclusions Endothelial ERK2/TP receptor pathway increases superoxide production and decreased NO bioactivity, resulting in deteriorating endothelial function, insulin resistance and steatohepatosis, which were improved by antagonist of the TP receptor in mice model of MetS. The present study indicates that ERK2/TP pathway could be a therapeutic target for complications of MetS.

Successful conception in a patient with PCOS using the integrated approach: A case report

Polycystic Ovary Syndrome (PCOS) is a condition that affects women of reproductive age resulting in hormonal, reproductive and metabolic abnormalities with an associated constellation of symptoms including disturbed menstrual cycle, hyperandrogenism, acne, weight gain, hair loss, diabetic predisposition, depression, mood swings and sub-fertility. Although a very complex disorder, PCOS can be managed optimally in some cases with the help of lifestyle intervention, nutritional therapy and Ayurveda. The subject of this study was a 30-year-old obese female with a clinical history of PCOS due to which she was unable to conceive. Her blood tests showed hyperinsulinism and borderline high cholesterol. She had low immunity and low energy coupled with high stress levels. The purpose of this case study was to determine the benefits of an Integrated Approach, that included nutritional therapy, ayurvedic herbs, vitamins, minerals, lifestyle modifications, along with exercise and counselling, in the management of PCOS and its comorbidities. During the 12-week treatment with the Integrated Approach, the patient lost 6 kg weight, felt more energetic, had reduction in fasting serum insulin levels, improved body composition, improved immunity and reduced stress that culminated in a successful pregnancy. Keywords: Integrated approach, PCOS, Ayurveda, Nutrition, Conception.

Effect of HCV treatment response on insulin resistance: A systematic review and meta-analysis.

Sustained virological response (SVR) in hepatitis C virus (HCV) patients treated with pegylated interferon α-2a and ribavirin is associated with reduced insulin resistance (IR), measured as a reduction of homeostasis model assessment (HOMA) scores after 24 weeks of therapy, and reduced fasting serum insulin and serum glucose levels. The present meta-analysis aimed to evaluate the effect of HCV treatment response on IR in HCV patients who achieved SVR and those who did not (non-SVR) after receiving interferon (IFN)-based therapy. The PubMed, Cochrane and Embase databases were searched using combinations of the following search terms: ‘HCV’, ‘hepatitis C’, ‘interferon’, ‘antiviral’, ‘treatment response’ and ‘insulin resistance’. The incidence of IR, HOMA-IR and HOMA-β, as well as fasting glucose and fasting insulin levels, were summarized in terms of basal values and values after the end of treatment for each study. A total of 8 studies were included in the final analysis. There was no significant difference in the reduction in IR between the SVR and non-SVR groups (odds ratio, 0.995; 95% CI=0.613–1.616; P=0.984). However, the SVR group had a significantly higher mean reduction in HOMA-IR (difference in means=−0.485; 95%CI=−0.713 to −0.256; P<0.001) and HOMA-β (difference in means=−15.448; 95%CI=−23.326 to −7.570; P<0.001) compared to the non-SVR group. In conclusion, HCV patients who achieved SVR after IFN-based therapy exhibited improvement in HOMA-IR and HOMA-β. The present results suggest that clinical management of IR and serum glucose levels may be an important way to impact the therapeutic response in HCV patients.

Vit D3 versus L Carnitine Supplement in Alleviating Age-Related Insulin Resistance in A Naturally Aging Rat Model

AbstractBackground: Insulin Resistance (IR) has long been rec-ognized as a characteristic of aging. Many studies recorded beneficial roles of Vitamin D3 (VD3) and L-Carnitine (LC) in obesity and type 2 diabetes.Aim of Study: To evaluate the role of VD3 versus LC in attenuating the age-related IR in a naturally aging rat model, clarifying their possible underlying mechanisms.Material and methods: Rats were divided into 4 groups; Young Control (YC), aged group, VD3-treated aged group (VD3-aged) and LC-treated aged group (LC-aged). Experi-mental procedures included measurement of body weight, Body Mass Index (BMI) and Oral Glucose Tolerance Tests (OGTT). The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index was also calculated. Assays of fasting serum glucose and insulin levels as well as serum tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6) and adiponectin levels were performed. Moreover, skeletal muscle Sirtuin-1 (SIRT-1), Triglycerides (TGs) and TNF-a levels alongside with the glucose transporter-4 (GLUt4) mRNA expression were assessed.Results: Compared to YC rats, aged rats exhibited signif-icant increase in fasting serum insulin and HOMA-IR as well as an abnormal OGTT. Serum TNF-a and IL-6 levels were significantly increased, whereas serum adiponectin level was significantly decreased in old rats. Furthermore, the SIRT1 levels and GLUT 4 mRNA expression were significantly lower, whereas the TGs and TNF-a were significantly higher in skeletal muscle of aged rats compared to YC ones. On the other hand, these parameters, were equally and significantly attenuated in VD3 and LC supplemented rats compared to non-treated age matched group, except for the skeletal muscle SIRT-1 level which could be elevated only by VD3, while the anti-inflammatory and TGs lowering effects of LC were more prominent than VD3. Nevertheless, the overall effect of VD3 and LC on IR-related parameters were nearly equal.Conclusion: Both VD3 or LC administrations were equally effective in alleviating the age-related IR, thus may provide a possible therapeutic intervention in the aging population.