Serum Insulin Concentrations Research Articles

Study of Glycemic Control by Ketogenic Diet Supplemented with Different Oils in Type II Diabetic Rats

In recent years, very low carbohydrate ketogenic diets (VLCKD) have been emphasized. While commonly debated and often opposed, these are clearly successful as a method for treating obesity, hyperlipidemia and diabetes at least in the short to medium term. Therefore, this research was conducted to investigate the impact of ketogenic diet (KD) supplemented with oil of either grape seed or fish and virgin olive on diabetic rats. Forty eight male albino rats weighing 200 to 210 g, were assigned into two main groups. The first group (n=8) was control negative group (-ve), the second main group (n=40) were intraperitoneally injected with a single dose of streptozotocin (STZ) [60 mg/kg b.w.] for induction of diabetes, then these rats were divided into five subgroups. Subgroup one was fed on the basal diet and served as a control positive group, while subgroup 2 was fed on KD only and subgroups from 3 to 5 were fed on KD supplemented with 4% oil of either grape seed or fish and virgin olive, respectively for 8 weeks. The results indicated that, STZ treated rats showed significant reduction (P≤0.05) in serum insulin concentration and increased glucose levels compared to normal rats. KD supplemented with oil of either grape seed or fish and virgin olive improved the biochemical changes due to diabetes. Furthermore, the intervention caused favorable changes in blood lipids and restored liver and kidney functions of the treated rats compared to the control positive group. In conclusion, the ketogenic diet and KD supplemented with oil of either grape seed or fish or virgin olive are potentially promising diets for diabetic patients دراسة التحکم في نسبة جلوکوز الدم بواسطة النظام الغذائي الکيتونى المدعم بالزيوت المختلفة في الفئران المصابة بمرض السکرى من النوع الثاني في السنوات الأخيرة ، کان هناک ترکيز متزايد على النظم الغذائية الکيتونية المنخفضة جدا فى الکربوهيدرات ، في حين يتم مناقشتها بشکل شائع ومعارضتها في کثير من الأحيان ، فمن الواضح أنها ناجحة کوسيلة لعلاج السمنة وفرط الدهون والسکرى على الأقل على المدى القصير إلى المتوسط. لذلک أجريت هذه الدراسة للتحقق من تأثير النظام الغذائي الکيتوني المدعم اما بزيت بذر العنب أوالسمک أوالزيتون البکر على الفئران المصابة بداء السکرى. تم استخدام عدد 48 من ذکور الفئران التي تزن 200 إلى 210 جم ، تم تقسيمهم الى مجموعتين رئيسيتين. تم الاحتفاظ بالمجموعة الرئيسية الأولى (ن = 8) کمجموعة ضابطة سالبة ، المجموعة الرئيسية الثانية تم استخدام عدد 40 من الفئران واستخدمت کمجموعة ضابطة موجبة تم حقنهم بمادة الاستربتوزوتين (60ملجم/کجم من وزن الجسم) لاحداث السکرى، ثم قسمت هذه الفئران إلى خمس مجموعات فرعية .تم تغذية المجموعة الفرعية الأولى على النظام الغذائي الأساسي واستخدمت کمجموعة ضابطة موجبة ، في حين تم تغذية المجموعة الفرعية 2 على النظام الغذائي الکيتوني فقط بينما تم تغذية المجموعات الفرعية من 3 إلى 5 على النظام الغذائي الکيتوني المدعم بنسبة 4% اما بزيت بذر العنب أوالسمک أوالزيتون البکر على التوالي . بعد 8 أسابيع ، تم ذبح الفئران وجمع عينات الدم للحصول على السيرم . اوضحت النتائج أن الفئران المعاملة بـالاستربتوزوتين أظهرت انخفاض معنوي (P≤0.05) في ترکيز الأنسولين في الدم وزيادة مستويات الجلوکوز مقارنة بالفئران الطبيعية. ادى النظام الغذائي الکيتوني المدعم بزيت بذر العنب أوالسمک أوالزيتون البکر في تحسين النتائج البيوکيميائية الناتجة عن مرض السکرى .علاوة على ذلک ، أدى التدخل إلى إحداث تغييرات إيجابية في صورة دهون الدم وتحسين وظائف الکبد والکلى للفئران المعالجة مقارنة بالمجموعة الضابطة الموجبة. الخلاصة إن النظام الغذائي الکيتوني والکيتونى المدعم بزيت بذر العنب أوالسمک أوالزيتون البکر هو نظام غذائي واعد محتمل لمرضى السکرى.

Dual mechanisms of a Sri Lankan traditional polyherbal mixture in the improvement of pancreatic beta cell functions and restoration of lipoprotein alterations in streptozotocin induced diabetic rats

Ethnopharmacological relevanceTraditional polyherbal preparations have been utilized in Sri Lanka since ancient times and have gained a wide acceptance throughout the country. Although an extensive body of evidence supports the use of traditional herbal mixtures in the treatment of diabetes mellitus, only a few polyherbal mixtures have been subjected to systematic scientific investigations and their mechanisms for long-term glucose control remain unclear. In general, scientific evaluations of the effectiveness of antidiabetic formulations which are prescribed by traditional practitioners have received great attention, and therefore uncovering their mechanism of action would be beneficial. AimThe aim of the present study was to investigate the therapeutic efficacy, in terms of antidiabetic and antihyperlipidaemic activities, of a well-known traditional polyherbal mixture composed of leaves of Murraya koenigii L., -cloves of Allium sativum L., - fruits of Garcinia quaesita Pierre and seeds of Piper nigrum L. in streptozotocin induced diabetic rats. Materials and methodsEqual amounts from each of the above plant parts (100 g) were mixed together and extracted into cold water, hot water (3 h, refluxed) and water-acetone (1:1) separately. Dose response study of cold water, hot water, and water-acetone extracts of the polyherbal mixture at three selected doses of 0.5 g/kg, 1.0 g/kg and 1.5 g/kg was conducted in streptozotocin (STZ) induced diabetic rats. Based on the dose response data, hot water and water-acetone extracts at the therapeutic dose of 1.0 g/kg were administered to STZ induced diabetic rats (n = 6/group) daily for 30 days in the long-term study. Glibenclamide (0.5 mg/kg) was used as the positive control. Glycaemic parameters, pancreatic β cell restoration, and lipid profile were evaluated in diabetic rats treated with the plant extract mixture. HPLC fingerprints of hot water and water-acetone extracts of the polyherbal mixture were compared with those of extracts of individual plants with the respective solvents, in the standardisation protocol. ResultsThe hot water and water-acetone extracts were shown to be active in the dose response study and 1.0 g/kg was selected for the long term study. Treatment with the hot water and water-acetone extracts of the polyherbal mixture and glibenclamide significantly lowered the glycated haemoglobin by 19%, 26%, and 43%, respectively, at the end of the intervention (p < 0.05). The serum insulin concentration was significantly increased (p < 0.05) upon the plant treatment, corroborating the evidence of β-cell restoration in the pancreas of H and E stained sections. Moreover, the above extracts reported an impressive restoration of lipoproteins in diabetic rats compared to the diabetic control rats. The homeostatic assessment of β-cell functions (HOMA-β) was also improved in rats treated with the hot water and water-acetone extracts of the polyherbal mixture. The HPLC fingerprints of the polyherbal mixture and the individual plants showed shifts in some peaks and formation of new peaks. ConclusionThe results revealed that the aforementioned polyherbal mixture possesses potent antihyperglycaemic and antihyperlipidaemic effects with considerable restoration of pancreatic β-cells, justifying the traditional use of the mixture in diabetes associated dyslipidaemia.

Protein restriction during late gestation in beef cow: effects on growth and meat quality of progeny

The objective of this study was determine whether the amount of protein provided to cows during late gestation would affect postnatal growth and lead to changes on glucose regulation, carcass characteristics and meat quality of steer progeny. At 121 d prepartum, 68 multiparous Angus cows were blocked by BW and expected calving date and randomly assigned to low protein level (LP, 6% CP) or high protein level (HP, 12% CP) and were allotted in 12 pens per treatment. After calving, cows were managed together on improved pastures until weaning. Calves were weighed and body measurements were recorded at birth. Blood samples were taken at birth and each 30 d until weaning at 180 d of age. Male calves were maintained as a group after weaning on native range until 23 month of age when individual steers were fed a finishing diet during 84 d before slaughter. Twenty days before the end of the finishing phase, steers were subjected to an intravenous glucose tolerance test. Body weight at birth tended to be great (P = 0.06) and body mass index was greater (P = 0.04) on HP than LP progeny. Maternal dietary protein concentration had no influence on offspring body weight and growth rate during lactation, rearing or finishing phases (P &gt; 0.10). Rib fat thickness of steers was not affected (P = 0.38) by maternal nutrition treatments, however, LM area was greater in HP steers than LP steers at entrance into the feedlot (P = 0.01) and end of finishing phase (P = 0.04). Glucose concentrations was greater (P &lt; 0.001) on LP calves than HP calves from birth to weaning without any change in insulin concentrations (P &gt; 0.10). Insulin-like growth factor concentrations was lower on LP calves at birth (P &lt; 0.05). During the glucose tolerance test at 24 month of age, glucose concentration after intravenous administration decreased faster (P = 0.002) in LP compared to HP steers. Peak of serum insulin concentration was greater (P = 0.04) and serum insulin concentration tended to decrease (P = 0.08) more rapidly in LP compared to HP steers. Hot carcass weight was similar between treatments (P = 0.69), however dressing percentage was increased in HP relative to LP steers (P = 0.01). Tenderness of Longissimus muscle was increased in HP compared to LP steers (P &lt; 0.001). No treatment differences in troponin-t degradation (P = 0.77) and collagen content (P = 0.58) were observed. Muscle fiber diameter was similar in LP and HP steers (P = 0.20), suggesting that increase of LM area in HP steers could be due to muscle hyperplasia. These data demonstrate that low protein during late gestation in bovine dams may affect fetal growth. Low level of protein compromised glucose regulation in early life and alter glucose regulation, enhancing insulin secretion in steer progeny at 24 month of age. The results indicated that level of protein during mid to late gestation does not affect offspring growth but has impacts on carcass composition and meat quality of steer progeny.

Protective Effects of Moderate Intensity Static Magnetic Fields on Diabetic Mice.

The purpose of this study was to investigate the effects of moderate-intensity static magnetic field (SMF) on diabetic mice. We studied the effects of SMF on blood glucose of normal mice by starch tolerance and glucose tolerance tests. Then, we evaluated the effects of SMF on blood glucose of diabetic mice by establishing alloxan-induced type 1 diabetic mice and high-fat diet + streptozotocin (STZ)-induced type 2 diabetic mice. The results showed that different magnetic field intensities and blank control did not affect the blood glucose of normal mice. After starch and glucose administration, different magnetic fields could improve the glucose tolerance of normal mice, and this was obvious in the600 mT group. In the experiment of type 1 diabetic mice induced by alloxan, the results showed that different magnetic field intensities could improve the starch tolerance of mice, and that in the 400 mT group was obvious. In the experiment of type 2 diabetic mice induced by a high-fat diet + STZ, the 400 mT group could reduce food intake and water consumption in the later period. The 600 mT group could improve the starch tolerance of mice. The 400 and 600 mT groups could reduce fasting blood glucose. At the same time, total cholesterol and triglyceride decreased in different magnetic field intensities, and the 600 mT group could significantly increase the serum insulin content of mice. In summary, the results of this study suggest that SMF has a protective role in diabetic mice. Bioelectromagnetics. © 2020 Bioelectromagnetics Society.

Immunotherapy against angiotensin II receptor ameliorated insulin resistance in a leptin receptor-dependent manner.

The angiotensin II type 1 receptor (AT1R) signaling pathway is reported to modulate glucose metabolism. Targeting AT1R, our group invented ATRQβ-001 vaccine, a novel immunotherapeutic strategy to block the activation of AT1R. Here, we evaluated the therapeutic efficacy of ATRQβ-001 vaccine in insulin resistance, and investigated the mechanism. Our results showed that ATRQβ-001 vaccine and specific monoclonal antibody against epitope ATR-001 (McAb-ATR) decreased fasting serum insulin concentration and improved glucose and insulin tolerance in ob/ob mice. These beneficial effects were verified in high-fat diet-induced obese mice. McAb-ATR activated insulin signaling in skeletal muscle and insulin-resistant C2C12 myotubes without affecting liver or white adipose tissue of ob/ob mice. Mechanistically, the favorable impact of McAb-ATR on insulin resistance was abolished in db/db mice and in C2C12 myotubes with leptin receptor knockdown. AT1R knockdown also eradicated the effects of McAb-ATR in C2C12 myotubes. Furthermore, McAb-ATR treatment was able to activate the leptin receptor-mediated JAK2/STAT3 signaling in skeletal muscle of ob/ob mice and C2C12 myotubes. Additionally, angiotensin II downregulated the leptin signaling in skeletal muscle of ob/ob and diet-induced obese mice. We demonstrated that ATRQβ-001 vaccine and McAb-ATR improved whole-body insulin resistance and regulated glucose metabolism in skeletal muscle in a leptin receptor-dependent manner. Our data suggest that immunotherapy targeting AT1R is a novel strategy for treating insulin resistance.

Pemafibrate, a PPAR alpha agonist, attenuates neointima formation after vascular injury in mice fed normal chow and a high-fat diet

Recently, the prevention of cardiovascular events has become one of the most important aims of diabetes care. Peroxisome proliferator-activated receptor (PPAR) agonists have been reported to have vascular protective effects. Here, we examined whether pemafibrate, a selective PPAR alpha agonist, attenuated neointima formation after vascular injury and vascular smooth muscle cell (VSMC) proliferation. We performed endothelial denudation injury in mice treated with a high-fat diet (HFD) or normal chow. Orally administered pemafibrate significantly attenuated neointima formation after vascular injury in HFD and normal chow mice. Interestingly, pemafibrate increased the serum fibroblast growth factor 21 concentration and decreased serum insulin concentrations in HFD mice. In addition, body weight was slightly but significantly decreased by pemafibrate in HFD mice. Pemafibrate, but not bezafibrate, attenuated VSMC proliferation in vitro. The knockdown of PPAR alpha abolished the anti-VSMC proliferation effect of pemafibrate. BrdU assay results revealed that pemafibrate dose-dependently inhibited DNA synthesis in VSMCs. Flow cytometry analysis demonstrated that G1-to-S phase cell cycle transition was significantly inhibited by pemafibrate. Pemafibrate attenuated serum-induced cyclin D1 expression in VSMCs. However, apoptosis was not induced by pemafibrate as assessed by the TUNEL assay. Similar to the in vitro data, VSMC proliferation was also decreased by pemafibrate in mice. These data suggest that pemafibrate attenuates neointima formation after vascular injury and VSMC proliferation by inhibiting cell cycle progression.

Evaluation of colostrum bioactive protein transfer and blood metabolic traits in neonatal lambs in the first 24 hours of life

Colostrum is a unique resource that contributes to the passive transfer of immunity and plays a central role in the health status of neonatal ruminants. However, digestion and absorption of colostral proteins in the gut remain incompletely understood. Therefore, this study aimed to investigate the effect of bovine colostrum feeding on blood metabolic traits and to quantify colostral bioactive proteins in the gastrointestinal digesta and blood to evaluate intestinal transfer in neonatal lambs in the first 24 h of life. Fifty-four newborn lambs were used in this study, including 27 lambs fed pooled bovine colostrum and slaughtered at 6 (C6h), 12 (C12h), or 24 h (C24h) after birth; 18 lambs not fed any colostrum or milk and slaughtered at birth (N0h) or 24 h (N24h) after birth; and 9 milk-fed lambs slaughtered at 24 h (M24h) after birth. Lambs receiving colostrum or milk were bottle-fed within the first 2 h to obtain intakes of 8% of body weight at birth. Samples of blood and digesta from the abomasum, jejunum, and ileum were collected after slaughter. Serum concentrations of glucose, insulin, total protein, and aspartate aminotransferase were higher in colostrum-fed lambs than in N0h lambs. Serum concentrations of insulin, total protein, insulin-like growth factor 1, and γ-glutamyl transpeptidase were higher in C24h lambs than in N24h or M24h lambs. Apparent efficiencies of IgG absorption in C6h, C12h, and C24h lambs were 14.4, 26.8, and 17.2%, respectively, whereas apparent efficiencies of lactoferrin (LF), α-lactalbumin (α-LA), and β-lactoglobulin (β-LG) absorption were very low in colostrum-fed lambs, with mean values of 0.06, 0.002, and 0.003%, respectively. Concentrations of IgG, LF, α-LA, and β-LG in the digesta of the abomasum, jejunum, and ileum rapidly decreased from C6h to C24h lambs, and the disappearance rates of IgG, LF, α-LA, and β-LG were higher in lambs from C6h to C12h (62.1, 75.7, 91.3, and 95.0% for IgG, LF, α-LA, and β-LG, respectively) than from C12h to C24h (34.6, 22.5, 7.5, and 2.2% for IgG, LF, α-LA, and β-LG, respectively). These results indicated that bovine colostrum feeding improved the metabolic and immunological status of lambs, and that ingested colostral IgG was prone to intact uptake into the blood, whereas almost all ingested LF, α-LA, and β-LG disappeared in the lumen of the gastrointestinal tract in a time-dependent manner. The findings provide novel information for exploring selective absorption of colostral compounds in the small intestine of lambs.

LncRNAH19 improves insulin resistance in skeletal muscle by regulating heterogeneous nuclear ribonucleoprotein A1

BackgroundSkeletal muscle is essential for glucose and lipid metabolism. Growing evidence reveals the importance of long non-coding RNAs (LncRNAs) in metabolism. This study aimed to investigate the function of LncRNA H19 (H19) in lipid metabolism of skeletal muscle and its potential mechanisms.MethodsGlucose tolerance, serum insulin and lipid content in serum and skeletal muscle were determined in control and H19-overexpressed db/db mice. Lipid metabolism was evaluated in H19-overexpressed or H19-silencing muscle cells by detecting lipid contents and mitochondria related functions. The underlying mechanisms were explored by RNA pull-down, mass spectrometry and RNA immunoprecipitation (RIP).ResultsH19 was downregulated in skeletal muscle of db/db mice. H19 overexpression in db/db mice inhibited lipid ectopic deposition in skeletal muscle, meanwhile improved glucose intolerance and insulin resistance as compared with control db/db mice treated with ad-GFP. Furthermore, overexpression of H19 reversed FFA-induced lipid accumulation and increased cellular respiration in muscle cells, while H19 knockdown exhibited opposite effects in muscle cells. Mechanistically, H19 interacted with heterogeneous nuclear ribonucleoprotein (hnRNPA1) which was validated by RNA pulldown and RIP analysis, which increased translation of fatty acid oxidation closely related genes PGC1a and CPT1b.ConclusionOur data suggest that overexpression of H19 ameliorates insulin resistance by reducing ectopic lipid accumulation in skeletal muscle. The possible underlying mechanisms are that overexpression of lncRNAH19 promotes fatty acids oxidation via targeting of hnRNPA1.3nDHbXWaWzN5EJ8oDSo3_JVideo abstract

Effect of high level of carbohydrate and supplementation of condensed tannins on growth performance, serum metabolites, antioxidant and immune response, and hepatic glycometabolism gene expression of Lateolabrax japonicus

Condensed tannins (CT) have been observed to be beneficial to maintain glucose homeostasis and improve carbohydrate utilization for livestock, whereas little information is available about the effects of CT on glycometabolism of fish. Three diets were formulated to contain approximately 15 % carbohydrate (G1), 39 % carbohydrate (G2), and G2 supplemented with 0.1 % CT. A total of 225 juvenile Lateolabrax japonicus were randomly assigned to 3 groups (triplicate tanks per group) with 25 fish in each tank and fed to apparent satiation during 56-d feeding trial. Results indicated that fish fed G2 had lower (p < 0.05) final body weight, weight gain rate, feed intake, specific growth rate and serum insulin concentration, but higher (p < 0.05) feed efficiency ratio and serum glucose, total antioxidant capacity, superoxide dismutase, immunoglobulin M and lipopolysaccharide than those fish fed G1 or G3. The activity of pyruvate kinase (PK) was lower (p < 0.05) but glucokinase (GK) was higher (p < 0.05) in G2 than in G1 or G3. Gene expression of insulin like growth factor Ⅰ and PK were down-regulated (p < 0.05), whereas GK was up-regulated (p < 0.05) in G2 than in G1 or G3. No difference (p> 0.05) in these gene expressions were observed between G1 and G3. It was concluded that L. japonicus fed diet with 39 % carbohydrate exhibited depressed growth performance, increased antioxidant and immune capacity, and hyperglycemia. Supplementation of 0.1 % CT resulted in improved growth performance and decreased serum glucose concentration, mainly due to the positive effects of CT on the activity and gene expression of hepatic glycolysis and gluconeogenesis enzymes of L. japonicus.

Catch-up growth in intrauterine growth-restricted piglets associated with the restore of pancreatic and intestinal functions via porcine glucagon-like peptide-2 microspheres

ABSTRACT Intrauterine growth restriction (IUGR) results in abnormal morphology and gastrointestinal function, such as reduced villi height and crypt depth, thinner mucosa and muscle layers, and reduced brush border enzyme activities, delayed gastric emptying, increased stress response. As a gastrointestinal growth factor, the manner by which the porcine glucagon-like peptide-2 (pGLP-2) microsphere administration restored the gastrointestinal function and growth performance of IUGR piglets was investigated. Fourteen newborn Duroc × (Yorkshire × Landrace) IUGR piglets (0.92 ± 0.113 kg) were assigned into the IUGR (negative control group) and pGLP-2 microsphere groups. The piglets in group pGLP-2 were intraperitoneally administered with 100 mg pGLP-2 microspheres on day 1 after birth. From days 15 to 26 of trial, the body weight of the pGLP-2 group was significantly higher than that of the control. IUGR piglets of group pGLP-2 showed a significantly increased pancreas weight, serum insulin content and activity of lipase and amylase. Injection of pGLP-2 microspheres restored the intestinal absorptive capacity by significantly increasing the mRNA expression of the sodium-glucose cotransporter 1 in the jejunum and the peptide transporter 1 in the jejunum. It also restored the redox balance by increasing the catalase mRNA expression and decreasing the heat shock protein 70 mRNA expression. In addition, this improvement was associated with the significant increase in gut diameter, length and weight. Therefore, it was concluded that the injection of pGLP-2 microspheres was a suitable therapeutic strategy for compensatory growth in low birth weight IUGR piglets.

Evaluation of angiopoietin-like protein 3 (ANGPTL3) levels in polycystic ovary syndrome

AimAngiopoietin-like protein 3 (ANGPTL3) is recognized as a regulator of lipid metabolism. However, little is known about its association with insulin resistance in polycystic ovary syndrome (PCOS) setting. The present study aimed to investigate the serum levels of ANGPTL3 and adiponectin in PCOS women compared to healthy controls. Main methodIn this study, a total of 175 premenopausal women (117 PCOS and 58 non-PCOS) were enrolled. Serum concentrations of ANGPTL3, adiponectin, fasting insulin, and other hormonal variables were measured using ELISA technique. Key findingsResults showed that adiponectin levels were significantly lower in PCOS group than those of non-PCOS group. However, serum levels of ANGPTL3, high-sensitivity C-reactive protein (hs-CRP), and homocysteine (Hcy) were found to be higher in PCOS patients, when compared to non-PCOS ones. Moreover, serum ANGPTL3 positively correlated with BMI and serum triglyceride, while it inversely correlated with serum HDL-C in PCOS patients. SignificanceOur results demonstrated that increased levels of ANGPTL3 correlated with insulin resistance and dyslipidemia in PCOS patients, highlighting the need for future studies targeting its role in the pathogenesis of this disease.

Dietary ingestion of 2-aminoanthracene (2AA) and the risk for type-1 diabetes (T1D)

Type 1 diabetes (T1D) is an autoimmune disorder caused by the destruction of insulin-secreting β-cells.T1D is on the rise around the world. Exposure to polycyclic aromatic hydrocarbons (PAHs) including 2-aminoanthracene (2AA) is considered a contributor to TID increase. The contribution of the ingestion of 2AA toward T1D vulnerability is examined. 2AA is found in a variety of household products. Juvenile male Sprague Dawley rats ingested various amounts of 2AA contaminated diet for 12 weeks. Results showed marginal reduction in body weight gain for the 100 mg/kg treated animals. Glucose tolerance test (GTT) indicated no changes at six weeks. However, at week 12, both treated groups had higher levels of blood glucose than the control group. Serum insulin concentration was elevated in the 50 mg/kg group while reduced in the 100 mg/kg animals. Serum lactate dehydrogenase activity was elevated in treated groups. Evaluation of pancreatic inflammatory cytokines revealed overexpression of IL-1B, IL-6, and IL-7. Apoptotic genes in the pancreas of exposed rats were overly expressed. Histopathology and insulin immunohistochemistry data showed the presence of mesenteric vessels surrounded by lymphocyte and enlarged size of islet cells respectively in the high dose group. These results suggest 2AA ingestion may enhance T1D development.

Insights from the clinical phenotype of subjects with Laron syndrome in Ecuador.

The Ecuadorian cohort of subjects with LS has taught us valuable lessons since the late 80's. We have learned about migration of Sephardic Jews to our country, their isolation in remote hamlets and further inbreeding. These geographical, historical and social determinants induced dissemination of a growth hormone (GH) receptor mutation which widely occurred in those almost inaccessible villages. Consequently, the world's largest Laron syndrome (LS) cohort emerged in Loja and El Oro, two of the southern provinces of Ecuador. We have been fortunate to study these patients since 1987. New clinical features derived from GH insensitivity, their growth patterns as well as treatment with exogenous insulin-like growth factor I (IGF-I) have been reported. Novel biochemical characteristics in the field of GH insensitivity, IGFs, IGF binding proteins (BP) and their clinical correlates have also been described. In the last few years, studies on the morbidity and mortality of Ecuadorian LS adults surprisingly demonstrated that despite obesity, they had lower incidence of diabetes and cancer than their relatives. These events were linked to their metabolic phenotype of elevated but ineffective GH concentrations and low circulating IGF-I and IGFBP-3. It was also noted that absent GH counter-regulation induces a decrease in insulin resistance (IR), which results in low but highly efficient insulin levels which properly handle metabolic substrates. We propose that the combination of low IGF-I signaling, decreased IR, and efficient serum insulin concentrations are reasonable explanations for the diminished incidence of diabetes and cancer in these subjects.

Altered Serum Amino Acid and Acylcarnitine Profiles in Hyperinsulinemic Hypoglycemia and Ketotic Hypoglycemia.

BackgroundIn addition to inborn metabolic disorders, altered metabolic profiles were reported to be associated with the risk and prognosis of some non-metabolic diseases, while as a rare metabolic disease, the overall secondary metabolic spectrum in congenital hyperinsulinemic hypoglycemia (HH) is largely undetermined. Therefore, we investigated metabolic profiles in HH patients and used ketotic hypoglycemia (KH) patients as a control cohort to unveil their distinct metabolic features.MethodsA total of 97 hypoglycemia children, including 74 with hyperinsulinemic hypoglycemia and 23 with ketotic hypoglycemia, and 170 euglycemia control subjects were studied retrospectively. Clinical and biochemical data were collected. The normoglycemic spectra of amino acids and acylcarnitines were determined by liquid chromatography tandem mass spectrometry. The serum insulin and fatty acid concentrations during standardized fasting tests in hypoglycemia patients were also collected. Receiver operating characteristic curve analysis was performed to screen potential biomarkers.ResultsAmong the normoglycemic spectra of amino acids, blood valine (p < 0.001), arginine (p < 0.001), threonine (p = 0.001), glutamate (p = 0.002), methionine (p = 0.005), ornithine (p = 0.008), leucine (p = 0.014), alanine (p = 0.017), proline (p = 0.031), citrulline (p = 0.042), aspartate (p = 0.046), and glycine (p = 0.048) levels differed significantly among the three groups. Significantly decreased levels of long- (C14:1, p < 0.001; C18, p < 0.001), medium- (C8, p < 0.001; C10, p < 0.001; C10:1, p < 0.001), and short-chain (C4-OH, p < 0.001; C5OH, p < 0.001) acylcarnitines were found in the hyperinsulinemic hypoglycemia group. Hyperinsulinemic hypoglycemia children with focal lesions and diffuse lesions had similar amino acid and acylcarnitine spectra. C10:1 < 0.09 μmol/L, threonine > 35 μmol/L, and threonine/C10:1 > 440 showed sensitivities of 81.1, 66.2, and 81.1% and specificities of 72.7, 78.3, and 81.8%, respectively, in distinguishing HH from KH.ConclusionsWe found significantly different altered serum amino acid and acylcarnitine profiles at normoglycemia, especially decreased C10:1 and increased threonine levels, between HH and KH children, which may reflect the insulin ketogenesis inhibition effect in HH patients; however, the detailed mechanisms and physiological roles remain to be studied in the future.

Short-term high-fat feeding induces a reversible net decrease in synaptic AMPA receptors in the hypothalamus

Dietary obesity compromises brain function, but the effects of high-fat food on synaptic transmission in hypothalamic networks, as well as their potential reversibility, are yet to be fully characterized. We investigated the impact of high-fat feeding on a hallmark of synaptic plasticity, i.e., the expression of glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) that contain the subunits GluA1 and GluA2, in hypothalamic and cortical synaptoneurosomes of male rats. In the main experiment (experiment 1), three days, but not one day of high-fat diet (HFD) decreased the levels of AMPAR GluA1 and GluA2 subunits, as well as GluA1 phosphorylation at Ser845, in hypothalamus but not cortex. In experiment 2, we compared the effects of the three-day HFD with those a three-day HFD followed by four recovery days of normal chow. This experiment corroborated the suppressive effect of high-fat feeding on hypothalamic but not cortical AMPAR GluA1, GluA2, and GluA1 phosphorylation at Ser845, and indicated that the effects are reversed by normal-chow feeding. High-fat feeding generally increased energy intake, body weight, and serum concentrations of insulin, leptin, free fatty acids, and corticosterone; only the three-day HFD increased wakefulness assessed via video analysis. Results indicate a reversible down-regulation of hypothalamic glutamatergic synaptic strength in response to short-term high-fat feeding. Preceding the manifestation of obesity, this rapid change in glutamatergic neurotransmission may underlie counter-regulatory efforts to prevent excess body weight gain, and therefore, represent a new target of interventions to improve metabolic control.

Pattern of postruminal administration of l-tryptophan affects blood serotonin in cattle

Serotonin (5-HT) has many important functions in both central and peripheral nervous systems. Although it has been demonstrated that manipulation of serotonin metabolism is possible in many species, there is limited information about l-tryptophan (TRP), a serotonin precursor, in cattle, and these provide conflicting results. Furthermore, there is no study evaluating how different patterns of intra-abomasal infusion of TRP impact circulating 5-HT. The objective of this study was to evaluate if intra-abomasal infusion patterns of TRP can affect circulating 5-HT and other metabolites from TRP metabolism in the plasma and serum and circulating glucose and insulin in cattle. Eight ruminally cannulated Holstein steers were used in a replicated 4 × 4 Latin square design. Each received intra-abomasal water infusion (control) or intra-abomasal TRP infusion (50 mg/kg BW) in 3 different patterns: a pulse infusion once a day (pulse once), pulse infusion twice a day (pulse twice), or continuous infusion (continuous). For continuous treatment, the TRP dose was diluted in tap water and infused by a peristaltic pump (300 mL/h). To equalize conditions, the other treatments had a water infusion (300 mL/h). The steers were fed every 2 h, and blood was collected from a jugular vein catheter every 4 h for 24 h after the initial infusion. Urine produced during the 24 h period was collected. Serum and plasma TRP, 5-HT and kynurenine, plasma glucose, and serum insulin concentrations were analyzed. Urine was analyzed for concentrations of 5-hydroxyindoleacetic acid. Both serum TRP and kynurenine were increased (P < 0.05) by all TRP infusion treatments, but concentrations in pulse dose treatments were greater than those in continuous infusion. Serum 5-HT increased (P < 0.05) with both pulse TRP infusion treatments; however, the continuous TRP infusion did not increase the serum 5-HT. Plasma 5-HT, glucose, and insulin had a tendency to increase with TRP pulse infusions. The urinary 5-hydroxyindoleacetic acid excretion was highest for pulse dose treatments. An acute supply of TRP in 1 or 2 daily doses increases serum 5-HT and increases circulating glucose and insulin in cattle. The TRP and kynurenine concentrations are similar in plasma and serum. However, the serum 5-HT concentration is more responsive to TRP administration than plasma.

Inhibition of fatty acid binding protein 4 attenuates gestational diabetes mellitus

Accumulatig evidence demonstrated that inflammation is associated with the development of gestational diabetes mellitus (GDM). Fatty acid-binding protein 4 (FABP4) was reported to be involved in immune response. However, the effect of FABP4 in GDM remians unclear. This study focused on the effect of FABP4 in GDM. C57BL/KsJdb/+ (db/+) mice were used for GDM mouse model . BMS-309403 (BMS) was used to inhibit FABP4 levels in GDM mouse model. IL-6 and TNF-α concentrations in serum were determined via ELISA. Serum glucose and insulin concentrations were tested using commercial glucometer and mouse insulin ELISA kit, respectively. IL-6 and TNF-α mRNA and protein levels were detected using RT-PCR and western blot, respectively. FABP4 levels were upregulated in GDM group compared with control group and were positively associated with serum IL-6 and TNF-α levels. FABP4 inhibition by BMS significantly decreased body weight and serum glucose concentrations, increasd serum insulin concentration, suppressed IL-6 and TNF-α expression both in the serum and the pancreas, enhanced little size and inhibited birth weight in GDM mouse model. Inhibition of FABP4 attenuates GDM in genetic mice.

Long-term nitrate administration increases expression of browning genes in epididymal adipose tissue of male type 2 diabetic rats

Expression of browning genes are lower in both humans and animals with type 2 diabetes (T2D). This study aims at determining effects of long-term nitrate administration on protein and mRNA levels of uncoupling protein 1 (UCP1), peroxisome proliferator activated receptor gamma (PPAR-γ), and PPAR-γ coactivator 1 alpha (PGC1-α) in epididymal adipose tissue (eAT) of rats with T2D. Male Wistar rats were divided into 4 groups (n = 6/group): Control, diabetes, control + nitrate (CN), and diabetes + nitrate (DN). T2D was induced using high fat diet combined with a low-dose of streptozotocin (30 mg/kg body weight). Sodium nitrate was administrated at a dose of 100 mg/L for 6 months in nitrate-treated rats. Fasting serum glucose and insulin concentrations were measured at months 0 (i.e. at start of the protocol), 3, and 6. At month 6, protein and mRNA levels of UCP1, PPAR-γ, and PGC1-α were measured in eAT samples. In addition, tissue concentration of cyclic guanosine monophosphate (cGMP) was measured and histological analyses were done at month 6. In rats with T2D, 6-month administration of nitrate decreased serum glucose and insulin concentrations by 13% and 23%, respectively and increased cGMP level by 85%. Rats with T2D had lower mRNA and protein levels of PPAR-γ (62%, P < 0.0001 and 18%, P = 0.0472), PGC1-α (49%, P = 0.0019 and 21%, P = 0.0482), and UCP1 (35%, P = 0.0613 and 30%, P = 0.0031) in eAT; 6-month nitrate administration restored these decreased levels to near control values. In addition, nitrate increased adipocyte density by 193% and decreased adipocyte area by 53% in rats with T2D. In conclusion, long-term low-dose nitrate administration increased mRNA and protein expressions of browning genes in white adipose tissue of male rats with T2D; these findings partly explain favorable metabolic effects of nitrate administration in diabetes.

Carnosic acid prevented olanzapine-induced metabolic disorders through AMPK activation.

Olanzapine, an atypical antipsychotic medication, has been associated with weight gain and metabolic toxicity, especially in long term usage. Carnosic acid (CA), a major constituent of rosemary extract, has been shown to improve metabolic abnormalities. In this experiment, the effect of CA on olanzapine-induced obesity and metabolic toxicity has been evaluated. Female Wistar rats were divided into six groups. (1) control; (2) olanzapine (5mg/kg/day, IP); (3, 4 and 5) olanzapine (5mg/kg/day, IP) plus CA (5, 10 and 20mg/kg/day, gavage) and (6) CA (20mg/kg/day, gavage). Bodyweight and food intake were measured during the study. After 14 days, mean systolic blood pressure (MSBP), glycemia, serum lipid profile, the serum concentration of leptin, insulin, AMPK, P-AMPK, and P-ACC liver protein levels were evaluated. The mean weight in the group received olanzapine increased by 4.8g at the end of the study. The average food intake was increased by olanzapine. Olanzapine increased triglyceride, fasting blood glucose (FBG), and leptin levels. It increased MSBP and down-regulated P-AMPK/AMPK ratio and P-ACC protein levels. CA (three doses) decreased body weight gain and reduced average food intake at 10 and 20mg/kg. CA especially at the highest dose decreased the changes in lipid profile, FBG, leptin level, and MSBP. P-AMPK/AMPK and P-ACC protein levels were increased by carnosic acid. In conclusion, the activation of AMPK by CA can be proposed as a key mechanism against olanzapine-induced metabolic toxicity where the activation of AMPK increases fat consumption and regulates glucose hemostasis in the liver.

Preliminary evidence of insulin resistance in young adults with impaired sleep

Objective Impaired sleep is associated with insulin resistance (IR), a precursor to type 2 diabetes mellitus (T2DM), but is poorly understood in young adults. This cross-sectional study examined sleep characteristics, risk factors for T2DM, and IR in college students. Participants: Thirty-two college students (18–25 years) with either short sleep or poor quality sleep were assessed. Methods: Participants completed self-report measures of sleep and T2DM risk factors. One week of objective sleep was measured with wrist actigraphy. IR was calculated from fasting serum glucose and insulin concentrations. Results: The sample slept on average 6.6 hours/night, and over half had IR. Of those with IR, 44.4% had normal body mass index (BMI), 72% had normal fasting glucose concentrations, and all but one had T2DM risk test score indicating they were not at risk. Conclusions: IR was found in over half of participants; however, many typical T2DM risk factors were not present in those with IR.