Increased Plasma Glucose Research Articles

Acclimation to constant and fluctuating temperatures promotes distinct metabolic responses in Arctic char (Salvelinus alpinus).

The Arctic is warming three times faster than the global average, imposing challenges to cold-adapted fish, such as Arctic char (Salvelinus alpinus). We evaluated stress and metabolic responses of Arctic char to different thermal acclimation scenarios to determine whether responses to thermal variation differed from those to stable exposures. Fish were exposed for 7 days to one of four treatments: (1) control (12°C); (2) mean (16°C), corresponding to the mean temperature of the diel thermal cycle; (3) constant high temperature (20°C); and (4) diel thermal cycling (12 to 20°C every 24 h). Exposure to 20°C causes increases plasma lactate and glucose, an imbalance in antioxidant systems, and oxidative stress in the liver. The 20°C treatment also elevated fractional rates of protein synthesis and caused oxidative stress in the heart. Stress responses were more pronounced in diel thermal cycling than in mean (16°C) fish, indicating that peak exposure temperatures or variation are physiologically important. Cortisol was highest in diel thermal cycling fish and oxidative stress was noted in the liver. Gill Na+/K+-ATPase activity was also significantly reduced in diel thermal cycling fish, suggesting gill remodeling in response to an osmoregulatory stress. Exposure to a constant 20°C was more challenging than a diel thermal cycle, demonstrating the importance of daily cooling to recovery. Arctic char inhabit a thermally variable environment and understanding how this impacts their physiology will be critical for informing conservation strategies in the context of a rapidly warming Arctic.

Atorvastatin ameliorates diabetic nephropathy through inhibiting oxidative stress and ferroptosis signaling.

Clinically, statins have long been used for the prevention and treatment of chronic renal diseases, however, the underlying mechanisms are not fully elucidated. The present study investigated the effects of atorvastatin on diabetes renal injury and ferroptosis signaling. A mouse model of diabetes was established by the intraperitoneal injection of streptozotocin (50 mg/kg/day) plus a high fat diet with or without atorvastatin treatment. Diabetes mice manifested increased plasma glucose and lipid profile, proteinuria, renal injury and fibrosis, atorvastatin significantly lowered plasma lipid profile, proteinuria, renal injury in diabetes mice. Atorvastatin reduced renal reactive oxygen species (ROS), iron accumulation and renal expression of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), transferrin receptor 1 (TFR1), and increased renal expression of glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor (NRF2) and ferritin heavy chain (FTH) in diabetes mice. Consistent with the findings in vivo, atorvastatin prevented high glucose-induced ROS formation and Fe2+ accumulation, an increase in the expression of 4-HNE, MDA and TFR1, and a decrease in cell viability and the expression of NRF2, GPX4 and FTH in HK2 cells. Atorvastatin also reversed ferroptosis inducer erastin-induced ROS production, intracellular Fe2+ accumulation and the changes in the expression of above-mentioned ferroptosis signaling molecules in HK2 cells. In addition, atorvastatin alleviated high glucose- or erastin-induced mitochondria injury. Ferroptosis inhibitor ferrostatin-1 and antioxidant N-acetylcysteine (NAC) equally reversed the expression of high glucose-induced ferroptosis signaling molecules. Our data support the notion that statins can inhibit diabetes-induced renal oxidative stress and ferroptosis, which may contribute to statins protection of diabetic nephropathy.

Exploring the Interactions between Obesity and Diabetes: Implications for Understanding Metabolic Dysregulation in a Saudi Arabian Adult Population.

The rising prevalence of obesity in Saudi Arabia is a major contributor to the nation's high levels of cardiometabolic diseases such as type 2 diabetes. To assess the impact of obesity on the diabetic metabolic phenotype presented in young Saudi Arabian adults, participants (n = 289, aged 18-40 years) were recruited and stratified into four groups: healthy weight (BMI 18.5-24.99 kg/m2) with (n = 57) and without diabetes (n = 58) or overweight/obese (BMI > 24.99 kg/m2) with (n = 102) and without diabetes (n = 72). Distinct plasma metabolic phenotypes associated with high BMI and diabetes were identified using nuclear magnetic resonance spectroscopy and ultraperformance liquid chromatography mass spectrometry. Increased plasma glucose and dysregulated lipoproteins were characteristics of obesity in individuals with and without diabetes, but the obesity-associated lipoprotein phenotype was partially masked in individuals with diabetes. Although there was little difference between diabetics and nondiabetics in the global plasma LDL cholesterol and phospholipid concentration, the distribution of lipoprotein particles was altered in diabetics with a shift toward denser and more atherogenic LDL5 and LDL6 particles, which was amplified in the presence of obesity. Further investigation is warranted in larger Middle Eastern populations to explore the dysregulation of metabolism driven by interactions between obesity and diabetes in young adults.

Levodopa attenuates the feed intake reduction caused by ergot alkaloids in cattle.

Consumption of ergot alkaloids from endophyte-infected tall fescue results in losses to the livestock industry in many countries and a means to mitigate these losses is needed. The objective of this study was to evaluate intra-abomasal infusion of the dopamine precursor, levodopa (L-DOPA), on dopamine metabolism, feed intake, and serum metabolites of steers exposed to ergot alkaloids. Twelve Holstein steers (344.9 ± 9.48kg) fitted with ruminal cannula were housed with a cycle of heat challenge during the daytime (32 °C) and thermoneutral at night (25 °C). The steers received a basal diet of alfalfa cubes containing equal amounts of tall fescue seed composed of a mixture of endophyte-free (E-) or endophyte-infected tall fescue seeds (E+) equivalent to 15 µg ergovaline/kg body weight (BW) for 9d followed by intra-abomasal infusion of water (L-DOPA-) or levodopa (L-DOPA+; 2mg/kg BW) for an additional 9d. Afterward, the steers were pair-fed for 5d to conduct a glucose tolerance test. The E+ treatment decreased (P = 0.005) prolactin by approximately 50%. However, prolactin increased (P = 0.050) with L-DOPA+. Steers receiving E+ decreased (P < 0.001) dry matter intake (DMI); however, when supplemented with L-DOPA+ the decrease in DMI was less severe (L-DOPA × E, P = 0.003). Also, L-DOPA+ infusion increased eating duration (L-DOPA × E, P = 0.012) when steers were receiving E+. The number of meals, meal duration, and intake rate were not affected (P > 0.05) by E+ or L-DOPA+. The L-DOPA+ infusion increased (P < 0.05) free L-DOPA, free dopamine, total L-DOPA, and total dopamine. Conversely, free epinephrine and free norepinephrine decreased (P < 0.05) with L-DOPA+. Total epinephrine and total norepinephrine were not affected (P > 0.05) by L-DOPA+. Ergot alkaloids did not affect (P > 0.05) circulating free or total L-DOPA, dopamine, or epinephrine. However, free and total norepinephrine decreased (P = 0.046) with E+. Glucose clearance rates at 15 to 30min after glucose infusion increased with L-DOPA+ (P < 0.001), but not with E+ (P = 0.280). Administration of L-DOPA as an agonist therapy to treat fescue toxicosis provided a moderate increase in DMI and eating time and increased plasma glucose clearance for cattle dosed with E+ seed.

Haematological, biochemical, enzymological changes and mitochondrial dysfunction of liver in freshwater climbing perch Anabas testudineus during their acute and chronic exposure to sodium fluoride

Anthropogenic activities are increasing fluoride concentration in watercourses. The present study focuses on the sublethal toxicity of sodium fluoride during sub-chronic and chronic time periods in the freshwater fish Anabas testudineus. The 96-hour LC50 value for fluoride was found to be 616.50 mg/L. Excessive mucous production and hyper excitability, followed by loss of balance, were seen in fish under acute fluoride exposure. Significant reduction in yield and specific growth rate of fish were assessed at 15, 30 and 45-days exposure intervals. Different bio-indicators like Hepatosomatic-index, Gonadosomatic-index and fecundity were reduced significantly in fish exposed to 10% (61.6 mg/L) and 20% (123.2 mg/L) of 96 h of LC50 values of fluoride in comparison to control. Toxicant concentrations directly correlated with parameter lowering. Fluoride exposure increased plasma glucose, creatinine, AST, and ALT and reduced total RBC, haemoglobin content, Hct (%), plasma protein, and cholesterol. Moreover, fluoride exposure significantly reduces the mitochondrial membrane potential in liver. This may result in metabolic depression, haematological, biochemical, and enzymological stress. The in-silico structural analysis predicts that fluoride may impede cytochrome c oxidase of the electron transport system, hence inhibiting mitochondrial functionality. These findings collectively highlight the urgent need for stringent regulation and monitoring of fluoride levels in freshwater ecosystems, as the subchronic and chronic effects observed in A. testudineus may have broader implications for aquatic ecosystems.

Evaluating thrombosis risk and patient-specific treatment strategy using an atherothrombosis-on-chip model.

Platelets play an essential role in thrombotic processes. Recent studies suggest a direct link between increased plasma glucose, lipids, and inflammatory cytokines with platelet activation and aggregation, resulting in an increased risk of atherothrombotic events in cardiovascular patients. Antiplatelet therapies are commonly used for the primary prevention of atherosclerosis. Transitioning from a population-based strategy to patient-specific care requires a better understanding of the risks and advantages of antiplatelet therapy for individuals. This proof-of-concept study evaluates the potential to assess an individual's risk of forming atherothrombosis using a dual-channel microfluidic model emulating multiple atherogenic factors in vitro, including high glucose, high cholesterol, and inflammatory cytokines along with stenosis vessel geometry. The model shows precise sensitivity toward increased plasma glucose, cholesterol, and tumour necrosis factor-alpha (TNF-α)-treated groups in thrombus formation. An in vivo-like dose-dependent increment in platelet aggregation is observed in different treated groups, benefiting the evaluation of thrombosis risk in the individual condition. Moreover, the model could help decide the effective dosing of aspirin in multi-factorial complexities. In the high glucose-treated group, a 50 μM dose of aspirin could significantly reduce platelet aggregation, while a 100 μM dose of aspirin was required to reduce platelet aggregation in the glucose-TNF-α-treated group, which proves the model's potentiality as a tailored tool for customised therapy.

Dietary flaxseed oil suppresses hyperglycemia and hyperinsulinemia through increasing in α-linolenic acid content in the muscle.

Types of fats and oils affect the onset of lifestyle diseases. In this study, we investigated the relationship between the postprandial hyperglycemia and fatty acids content in the skeletal muscle of C57BL/6 mice given 20% lard, palm oil, corn oil, safflower oil, and flaxseed oil for 16 weeks. Lard increased plasma glucose and insulin levels at the end of feeding period, whereas flaxseed oil did not. It was noteworthy that there is a positive correlation between palmitic acid content in the muscle and postprandial hyperglycemia, and a negative correlation between α-linolenic acid content and hyperglycemia. Alternatively, mice were given 30% lard for 16 weeks. When lard was partially substituted with flaxseed oil (10-50% substitution), flaxseed oil dose-dependently prevented lard-induced hyperglycemia and hyperinsulinemia. In conclusion, flaxseed oil prevents the adverse effects of lard through increasing in α-linolenic acid content in the muscle.

Psychosocial Well-being among Diabetic Individuals

Background: Quality of life (QoL) assessment is considered an important outcome measure in chronic disease management. With an increase in the prevalence of diabetes in India, it becomes imperative to assess QoL in diabetic patients for their better care and control. The present study aimed to assess the QoL among diabetic patients attending the diabetic outpatient clinic and probe its association with glycemic status and management. Methodology: A cross-sectional study was conducted for 4 months among 185 type 2 diabetes mellitus (T2DM) patients. Information on sociodemographic profile, diabetic history, and current medications was obtained. QoL was assessed using the General Health Questionnaire-28 (GHQ-28). The results were statistically analyzed. Results: Using GHQ-28, the psychosocial components of the patients in the fields related to somatic symptoms, anxiety and insomnia, social dysfunction, and severe depression were assessed. Significantly higher GHQ scores (P &lt; 0.05) were noted in T2DM patients with higher glycated hemoglobin and increased plasma glucose levels, suggesting stronger associations of poorer QoL with compromised glycemic status. Insulin users exhibited higher GHQ scores (higher scores for depression subdomains) compared to noninsulin users. QoL was also found significantly dependent on the duration of diabetes and other comorbidities. Conclusion: The psychosocial well-being of the patients is significantly impacted in cases of chronic ailments like diabetes which adds to the total disease burden eventually. The present study warrants periodic assessment of QoL in diabetic individuals as a part of routine care along with advise of psychiatric counseling for those in need.

Yeast polysaccharide supplementation: impact on lactation, growth, immunity, and gut microbiota in Dezhou donkeys.

The Dezhou donkey, a prominent Chinese breed, is known for its remarkable size, rapid growth, and resilience to tough feeding conditions, and disease resistance. These traits are crucial in meeting the growing demand for Ejiao and donkey meat. Yeast polysaccharide (YPS), a functional polysaccharide complex known for its immune-enhancing and growth-promoting properties in livestock and poultry, remains relatively understudied in donkeys. This study aimed to investigate the impact of YPS supplementation on lactating and growing Dezhou donkey jennies and foals. Twelve 45-day-old Dezhou donkey foals and their jennies, matched for body weight and age, were randomly allocated to two dietary groups: a control group receiving a basal diet and an experimental group receiving the basal diet supplemented with 10 g/pen of YPS. The experiment was conducted over a 23-day period, during which donkey foals and lactating jennies were co-housed. The findings revealed that YPS supplementation had no adverse effects on milk production or composition in Dezhou donkey jennies but significantly increased feed intake. Additionally, YPS was associated with increased plasma glucose and creatinine concentrations in foals, while tending to decrease alkaline phosphatase, white blood cell count, red blood cell count, and hemoglobin levels (p < 0.10). Immune indices demonstrated that YPS supplementation elevated the levels of immunoglobulin A (IgA) and immunoglobulin G (IgG) in jennies (p < 0.05) and increased complement component C4 concentrations in foals (p < 0.05). Moreover, YPS positively influenced the fecal microbiome, promoting the abundance of beneficial microorganisms such as Lactobacillus and Prevotella in donkey foals and Terriporobacter and Cellulosilyticum in jennies, all of which contribute to enhanced feed digestion. Additionally, YPS induced alterations in the plasma metabolome for both jennies and foals, with a predominant presence of lipids and lipid-like molecules. Notably, YPS increased the concentrations of specific lipid metabolites, including 13,14-Dihydro PGF2a, 2-Isopropylmalic acid, 2,3-Dinor-TXB2, Triterpenoids, Taurocholic acid, and 3b-Allotetrahydrocortisol, all of which are associated with improved animal growth. In conclusion, this study suggests that dietary supplementation of YPS enhances feed intake, boosts immunity by increasing immunoglobulin levels, stimulates the growth-promoting gut microbiota (Lactobacillus and Prevotella), and exerts no adverse effects on the metabolism of both Dezhou donkey jennies and foals.

Abstract 19008: ATP-Dependent Citrate Lyase Drives Cardiac Left Ventricular Dysfunction by Metabolic Remodeling

Introduction: Cardiovascular diseases and cancer are the leading causes of death worldwide. Recurrent mutations of metabolic enzymes in cancer cells benefit tumor growth, creating a systemic metabolic phenotype and increasing the risk for adverse cardiac events. Computational analysis revealed an oncometabolic phenotype in the heart, characterized by a switch from oxidative towards reductive carboxylation of α-ketoglutarate and citrate. Our studies identified the ATP citrate lyase (ACL) as a critical regulatory enzyme driving metabolic adaptation during cancer by increasing acetyl-CoA synthesis and histone 3 acetylation in the heart. Hypothesis: We hypothesized that ACL is crucial for cardiac adaptation during oncometabolic stress. Methods: To answer these questions, we developed a cardiac-specific mouse model lacking ATP citrate lyase using clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas)9 genomic editing. Cas9-Myh6-dtTomato mice (n=14-17 male and female mice/group) were subcutaneously injected 6 days after birth with single gRNA targeting the Acly locus. Cardiac function was monitored using echocardiographic examinations weekly between 12 and 20 weeks. We used in vivo [ 18 F]-FDG-positron emission tomography (PET) and stable isotope tracer labeling to identify and quantify metabolic alterations in vivo in response to the loss of ACL. Results: Knockdown of ACL causes left ventricular systolic dysfunction as evidenced by significantly reduced ejection fraction and an increased left ventricular diameter. In vivo [ 18 F]-FDG-PET revealed that loss of ACL increased plasma glucose uptake which is consistent with maladaptive metabolic remodeling and impaired oxidative metabolism during heart failure. RNA-sequencing followed by pathway enrichment analysis revealed differential expression of genes involved in mitochondrial function and lipid metabolic processes. Mass spectrometry-based metabolic flux analysis showed an increased malate m+2 to citrate m+2 ratio, consistent with reduced citrate efflux from the mitochondria towards the cytosol. Conclusions: ACL activity regulates reductive citrate flux and drives metabolic adaptation associated with cardiac dysfunction

Determination of Blood Biochemistry Reference Intervals in Eastern Collared Lizards (Crotaphytus collaris)

Abstract Eastern collared lizards (Crotaphytus collaris) are growing in popularity as exotic pets in the United States and worldwide. However, clinical biochemistry reference data to support interpretation of health and disease for this species remains lacking. This study evaluated 87 apparently healthy Eastern collared lizards (Crotaphtyus collaris). Blood samples were collected from the ventral coccygeal vein and assayed via Abaxis VetScan VS2 and Avian Reptile rotor. While lizard weight and snout-vent length (SVL) were normally distributed, most biochemical analytes, except albumin and total protein, were not. Many analytes were affected, albeit slightly, by lizard age, SVL, body condition score, gravidity and/or recent ovoposition, sex, health status, and color/locality. However, except for calcium, phosphorous, and albumin for gravid or immediately post oviposition females, biochemical values remained within the generated reference interval. Limitations of this study included that the VetScan VS2 avian / reptile profile plus rotor was unable to successfully provide values for bile acids for most of these apparently healthy lizards. When compared to biochemistry analyte values of lizards from the suborder Iguania from the western hemisphere, Eastern collared lizard biochemistries were similar for some analytes, but a relatively increased plasma glucose and uric acid occurs in this species which could affect the diagnosis of clinical disease or other health abnormalities.

SAT077 Association Of Mitochondrial DNA With Type-2-diabetes, Glucose Level, And Insulin Resistance

Abstract Disclosure: M. Heydarpour: None. L. Pojoga: None. J.R. Romero: None. G.H. Williams: None. J.S. Williams: None. Background: Mitochondrial dysfunction leads to decreased Adenosine-3-phosphate (ATP) production and increased ROS production, leading to insulin resistance, and diabetes (T2D). Mutations in mitochondrial DNA (mtDNA) have been associated with increased ROS production. Current studies have shown a role for mtDNA variants in the pathogenesis of both T2D and insulin resistance. Despite both of these disorders are controlled by many features involving interplay between genetic and environmental factors, however amongst genetic factors, variations in mtDNA have shown a potential role in the risk of T2D. We analyzed the genomic influence of mtDNA on T2D, insulin resistance, and fasting plasma glucose in humans. Methods: Participants (113 cases with T2D and 303 controls) from the HyperPATH Cohort were selected and genotyped using a Multi-Ethnic-Genotyping-Array. Individuals consumed two study diets containing high (&amp;gt;200mEq/day) and low (&amp;lt;10mEq/day) sodium content for 7 days each. The Homeostasis Model Assessment (HOMA-IR) index was used to assess insulin resistance. We performed association analyses between 275 mitochondrial genetic markers (SNVs) and three outcomes (T2D, insulin resistance, and fasting plasma glucose) using PLINK program. Results: We identified 2 significant SNVs within mtDNA that associated with T2D after adjusting the model for sex, age, study site, and BMI. One SNV (rs2248727, OR=3.15, P=0.00035) was within the coding region of Cytochrome C Oxidase III (COX3) and another (rs2857284, OR=3.13, P=0.00037) within the coding region of NADH Dehydrogenase subunit 4 (ND4). Further, we identified 2 SNVs associated with fasting plasma glucose; rs28359176, beta=22.7, P=0.0006 in the coding region of NADH Dehydrogenase subunit 5 (ND5), and rs367951226 beta=22.7, P=0.0006) in the region of ATP Synthase membrane subunit 6 (ATP6). We also identified a significant signal (rs376888742, beta=5.61, P=6.09E-06) associated with insulin-resistance in the coding region of Cytochrome B (CYB). Conclusion: These results show a significant association between mitochondrial ND4 and COX3 gene variants with T2D and CYP with insulin resistance. Gene variants of mitochondrial ND5 and ATP6 were associated with increase plasma glucose. Presentation: Saturday, June 17, 2023

The uninhibited glucagon signaling pathway in Japanese flounder Paralichthys olivaceus: A link with the glucose intolerance?

The study aimed to explore the role of glucagon in regulating glucose metabolism and gain insight into the reasons for glucose intolerance in carnivorous fish. Firstly, Japanese flounder was injected intraperitoneally with glucagon and small interfering RNA (siRNA) targeted glucagon receptor a (GCGRa), cAMP-response element binding protein 1 (CREB1), and peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α). Secondly, a two-week feeding trial was conducted with Japanese flounder fed diets with 11.95% and 31.96% dietary carbohydrates, respectively. At the start and 7th day of the feeding trial, flounders fed each diet were intraperitoneally injected with saline or siGCGRa. Furthermore, the fish were separated into two groups and fasted for 72 h. Saline and siGCGRa were injected respectively at 6 h after feeding. The results showed that glucagon activated gluconeogenesis in the liver, leading to an elevation of plasma glucose levels, while interference of GCGRa, CREB1, and PGC-1α caused the opposite results. Elevated dietary carbohydrate intake increased plasma glucose and insulin levels. Meanwhile, the glucagon signaling pathway was activated. After interference with the GCGRa, plasma glucose decreased, and the glucagon pathway was inhibited. The plasma insulin increased, and the mRNA expression of protein kinase B β (akt2) was up-regulated accordingly. In addition, upon injecting siGCGRa, it was observed that gluconeogenesis in the liver and plasma glucose levels during fasting were reduced in comparison to the control group. In contrast, plasma insulin levels and the transcription levels of akt2 and glucokinase (gck) in the liver exhibited an increase. In summary, the uninhibited glucagon signaling pathway promoted gluconeogenesis and suppressed the action of insulin in Japanese flounder, which might be the reason for the glucose intolerance.

Cold Exposure Regulates Hepatic Glycogen and Lipid Metabolism in Newborn Goats.

Cold exposure influences liver metabolism, thereby affecting energy homeostasis. However, the gene regulatory network of the liver after cold exposure remains poorly understood. In this study, we found that 24 h cold exposure (COLD, 6 °C) increased plasma glucose (GLU) levels, while reducing plasma non-esterified fatty acid (NEFA) and triglyceride (TG) levels compared to the room temperature (RT, 25 °C) group. Cold exposure increased hepatic glycogen content and decreased hepatic lipid content in the livers of newborn goats. We conducted RNA-seq analysis on the livers of newborn goats in both the RT and cold exposure groups. A total of 1600 genes were identified as differentially expressed genes (DEGs), of which 555 genes were up-regulated and 1045 genes were down-regulated in the cold exposure group compared with the RT group. Cold exposure increased the expression of genes involved in glycolysis, glycogen synthesis, and fatty acid degradation pathways. These results can provide a reference for hepatic lipid and glycogen metabolism in newborn goats after cold exposure.

Upaya Mengenali Sindrom Kardiometabolik melalui Pengabdian kepada Masyarakat

Introduction: The Healthy Adjusted Life Expectancy Index (HALE) for 2019 for the Indonesian population is 62.8 years lower than the 71.3 years for standard life expectancy; this is due to the lack of quality of life in Indonesia. The profile of the population in Central Java for the elderly category every year is similar to the increase on a national scale. The fact that the elderly are still working to earn a living indicates that their welfare level is still low. Non-communicable diseases (NCDs) are often the cause of premature death before the age of 70. Cardiovascular disease is the number-one killer in the world. Cardiometabolic syndrome is characterized by at least three things: abdominal obesity, increased plasma glucose, increased blood pressure, increased triglycerides, and decreased HDL cholesterol. A study on five members found an average total cholesterol level of 168.9 mg/dl and an average blood pressure of 125.4/80.9 mmHg. Objective: The aim of this community service is to increase awareness and the health status of members of the hypertension care group in Mersi Purwokerto. Methods: This community service method involves coordination with the chief of the hypertension care group, making leaflets, and preparing tools and materials for cholesterol examination. Results: This community service received good active participation from members of the hypertension care group in Mersi, Purwokerto. Overview of the risk of metabolic syndrome in community service participants, namely 32 DM sufferers (55.2%), 25 hypertension sufferers (43.1%), and 45 with high total cholesterol levels (77.6%). Conclusion: The results of this community service are expected to be a screening for participants who have a high risk of cardiometabolic syndrome and a desire to continue to make active and healthy lifestyle changes.

Supplementation of an organic mineral source modulated metabolic profile, insulin sensitivity, and oxidative stress in dairy calves with different birth body weights

The present study was conducted to investigate the effects of partial replacement of inorganic minerals (IM) with advanced chelated minerals (ACMS) in the starter diets of calves of different birth body weights (BBW) on metabolic indices and glucose tolerance test. Fifty-two Holstein calves were assigned to one of 4 treatments in a 2 × 2 factorial arrangement with two mineral sources (IM or ACMS) and two BBW (low or normal birth weight; LBW or NBW). Calves were weaned on day 56 and remained in the study until day 71 of the study. Blood samples for blood metabolite analysis were collected from the jugular vein on days 30, 60, and 70 of the study, and for hematology on days 36, 56, and 70. The results showed that the interaction of starter mineral sources (MS) and BBW affected the overall plasma concentration of β-hydroxybutyrate (BHB), with the highest value being obtained during treatment with LBW-ACMS. In addition, an interaction between MS and BBW was observed in plasma insulin concentrations, with LBW-IM calves having the lowest concentrations compared to the other treatments. Plasma albumin concentrations were lower in LBW calves than in NBW calves. In addition, NBW calves had greater plasma concentrations of glucose (day 60), insulin (day 30), BHB (day 30), and malondialdehyde (MDA; day 60 and the overall period) than LBW calves, while total antioxidant capacity (TAC) tended to reverse at day 70. The ACMS starter increased plasma glucose concentration at day 30 and tended to increase plasma BHB concentration in the overall period. In addition, plasma MDA concentrations were lower in calves receiving ACMS than in calves receiving IM during the overall period. NBW calves tended to have more eosinophils (day 70), basophils (day 36), and erythrocytes (RBC, day 56, and the overall period) in plasma than LBW calves. Regardless of BBW, feeding ACMS starter increased white blood cells (WBC), neutrophils, and eosinophils at day 70 and also tended to increase neutrophils during the overall period compared with the IM groups. Red blood cell concentrations were greater in calves fed ACMS than in calves fed IM during the overall period. Glucose tolerance test showed that basal glucose concentration and clearance rate (CR) of glucose tended to be lower and higher, respectively, in calves fed ACMS than in calves fed IM. ACMS supplementation increased basal concentrations and also tended to increase maximum insulin concentrations compared with IM supplementation. In addition, calves receiving ACMS starter had greater plasma insulin area under the curve (AUC) and CR compared with calves receiving IM. Feeding ACMS tended to increase the ratio CR of insulin to CR of glucose and increased the AUC of insulin to AUC of glucose compared with feeding IM. Overall, feeding ACMS resulted in a decrease in plasma MDA concentration and an increase in neutrophil concentration, suggesting that ACMS may improve immune function in these calves. A potential insulinotropic effect was noted with ACMS feeding, which was accompanied by an improvement in glucose control rate. This is likely due to higher bioavailability of chelated minerals such as Zn and should be further investigated.

Changes in hypothalamic mu-opioid receptor expression following acute olanzapine treatment in female rats: Implications for feeding behavior

Advances have been made in recent years in using opioid receptor antagonists as an adjunct therapy to psychotropic medication to reduce debilitating weight gain and metabolic adverse effects associated with in particular second generation antipsychotics. However, it is unknown whether second generation antipsychotics produce a change in opioid receptor expression in the brain. The present study investigated early changes in opioid receptor expression in the female rat hypothalamus, a master controller of hunger and metabolic regulation, after acute treatment with olanzapine, a commonly used second generation antipsychotic. Using quantitative spatial in situ hybridization and receptor autoradiography, expression levels of the three opioid receptors; kappa, mu and delta, were determined at mRNA and protein level, respectively, in the five hypothalamic areas: paraventricular nucleus, arcuate nucleus, ventromedial nucleus, dorsomedial nucleus and lateral hypothalamus. After 48 h of olanzapine treatment at clinically relevant plasma concentration weight gain and food intake changes, and increased plasma glucose were observed in female rats. Olanzapine treatment also led to a significant increase in mu opioid receptor availability in the arcuate nucleus, which contains both satiety and hunger controlling neurons. No other areas showed any opioid receptor expressional changes with olanzapine treatment on neither at mRNA nor protein level. Technical difficulties made it impossible to analyze mRNA levels in the lateral hypothalamus and overall binding of delta opioid receptors. Thus, the present study provided insights in to how olanzapine at clinically relevant plasma levels already at an early stage modulated the opioid system in the hypothalamus.

Increasing the prepartum dose of rumen-protected choline: Effects of maternal choline supplementation on growth, feed efficiency, and metabolism in Holstein and Holstein × Angus calves

Feeding pregnant cows rumen-protected choline (RPC) may have the potential to affect the growth and health of offspring, but little is known about the optimal dose, or the potential mechanisms of action. The objectives of this experiment were to 1) determine if increasing RPC supplementation during late gestation in multiparous Holstein cows would improve calf growth and 2) determine if maternal choline supplementation alters global DNA methylation patterns. Pregnant multiparous Holstein cows (n = 116) were randomly assigned to diets targeting 0g choline ion (0.0 ± 0.000 choline ion, %DM, control; CTL), 15g of choline ion (recommended dose; RD) from an established RPC product (0.10 ± 0.004 choline ion, %DM, RPC1RD; ReaShure, Balchem Corp.; positive control), or 15g (0.09 ± 0.004 choline ion, %DM, RPC2RD) or 22g (0.13 ± 0.005 choline ion, %DM, high dose; RPC2HD) of choline ion from a concentrated RPC prototype (RPC2; Balchem Corp.). Treatments were mixed into a total mixed ration and cows had ad libitum access via a roughage intake control system (Hokofarm Group, Marknesse, Netherlands). All female Holstein (n = 49) and Holstein × Angus calves (male, n = 18; female, n = 30) were enrolled and fed colostrum from a cow within the same treatment. Holstein calves and Holstein × Angus calves were fed an accelerated and traditional milk replacer program, respectively, and offered ad libitum access to calf starter. Jugular vein blood samples were collected, and body weight was measured at 7, 14, 28, 42, and 56 d of age. Categorical treatment and continuous effects of actual prepartum maternal choline ion intake were analyzed using mixed effect models. An interaction of treatment with sex, nested within breed, resulted in any choline treatment increasing the proportion of methylated whole blood DNA in male, but not female calves. Although 37% of Holstein calves across all treatments experienced abomasal bloat, no evidence for differences in health measurements (signs of respiratory disease and fecal consistency) were observed across treatments. During the first 2 wk of life in Holstein calves, RPC2HD tended to increase average daily gain (ADG) and feed efficiency (FE) compared with CTL and increasing maternal choline ion intake linearly increased ADG and FE. Maternal choline supplementation increased plasma glucose compared with CTL, while increasing serum insulin-like growth factor-1 and decreasing serum lipopolysaccharide binding protein at 7 d of age in Holstein calves. In Holstein × Angus calves, the effect of treatment on ADG tended to interact with sex: in males, RPC2HD increased ADG after 2 wk of life compared with CTL, without evidence of a treatment effect in female calves. Increasing maternal choline ion intake linearly increased ADG after 2 wk of age in male Holstein × Angus calves, while quadratically increasing FE in both sexes. Altered global DNA methylation patterns in male Holstein × Angus calves, and changes in blood metabolites in Holstein calves, provide 2 potential mechanisms for observed improvements in calf growth. Continuous treatment models demonstrated that the effects of maternal choline supplementation are sensitive to the amount of maternal choline ion intake, with greater benefit to calves observed at higher maternal intakes.

Rutin forestalls dysregulated cardiac bioenergetics in bisphenol A and dibutyl phthalate-exposed rats through PPARα and AMPK modulation

Objectives: Proper cardiac function is greatly dependent on adequate supply and metabolism of energy substrates. Environmental pollutants exposure including plasticizers can trigger adverse cardiac metabolic events. This study was designed to investigate the ameliorative effect of rutin (Rt) on dysregulated cardiac energy metabolism in plasticizer-exposed rats. Materials and Methods: Forty-two rats were randomised into seven groups (n = 6): Control (0.1% dimethyl sulfoxide), bisphenol A (BPA, 25 mg/kg, p.o), dibutyl phthalate (DBP, 25 mg/kg, p.o), BPA + Rt 25 mg/kg, Rt 50 mg/kg, DBP + Rt (25 mg/kg, Rt 50 mg/kg), BPA + DBP and BPA + DBP + Rt, daily for 21 days. Results: BPA and DBP exposure increased plasma glucose, reduced insulin, and increased plasma and cardiac free fatty-acid. Cardiac glucose-6-phosphate level, hexokinase and pyruvate dehydrogenase activities increased in DBP while BPA reduced these variables. Cardiac glucose transporter-4 expression was reduced in BPA group, while cardiac peroxisome proliferator-activated receptor-alpha (PPARα) and AMP-activated protein kinase (AMPK) expression increased in BPA and DBP-treated rats. However, Rt administration prevents impaired cardiac bioenergetics and glucometabolic regulation. Conclusion: Summarily, Rt improves BPA and DBP-impaired cardiac bioenergetics through PPARα and AMPK modulation.

Optimization of a glucagon-like peptide 1 receptor antagonist antibody for treatment of hyperinsulinism.

Congenital hyperinsulinism (HI) is a genetic disorder in which pancreatic beta cell insulin secretion is excessive and results in hypoglycemia that can cause brain damage or death without treatment. Most patients with loss-of-function mutations in ABCC8 and KCNJ11, the genes encoding the beta cell ATP sensitive potassium channel (KATP), are unresponsive to diazoxide, the only FDA approved medical therapy, and require a pancreatectomy. The glucagon-like peptide 1 receptor (GLP-1R) antagonist exendin-(9-39) is an effective therapeutic agent to inhibit insulin secretion in both congenital and acquired hyperinsulinism. Previously, we identified a highly potent antagonist antibody, TB-001-003, which was derived from our synthetic antibody libraries that were designed to target G protein-coupled receptors. Here, we designed a combinatorial variant antibody library to optimize the activity of TB-001-003 against GLP-1R and performed phage-display on cells overexpressing GLP-1R. One antagonist, TB-222-023, is more potent than exendin-(9-39), also known as Avexitide. TB-222-023 effectively decreased insulin secretion in primary isolated pancreatic islets from a mouse model of hyperinsulinism, Sur1-/- mice, and in islets from an infant with HI as well as increased plasma glucose and decreased the insulin to glucose ratio in Sur1-/- mice. These findings demonstrate that targeting GLP-1R with an antibody antagonist is an effective and innovative strategy for treatment of hyperinsulinism.