Alter Plasma Glucose Research Articles

Calcium propionate is an alkalizing agent in exercising Standardbreds

The objective of this study was to determine if calcium propionate is an alkalizing agent in exercising Standardbreds and if it alters plasma glucose and serum insulin concentrations. This study used a randomized crossover design to test the hypotheses that calcium propionate alters total CO2 (tCO2), Ca++, pH, strong ion difference (SID), glucose, and insulin in Standardbreds completing a simulated race test (SRT) on a high-speed equine treadmill. Blood was collected from eight horses (mean age ± SD = 16 ± 2.7 years; range = 13 - 21 years) at 10 and 5 min prior to treatment or control administration, just prior to the subsequent SRT, directly after the SRT, and at 60- and 90-min post SRT. Plasma pH and plasma concentrations of tCO2, glucose, Ca++, and Na+, K+, Cl-, Lac- (for SID calculation) were measured in duplicate by blood gas analyzer and serum insulin by radioimmunoassay. Data were analyzed by two-way repeated-measures ANOVA. For plasma pH, Na+, K+, Cl-, Lac-, SID, insulin and glucose, no effects of treatment or treatment by sampling-timepoint interaction were found (p>0.05). Plasma tCO2, Ca++, pH, Na+, SID, and glucose concentrations were significantly lower, and Lac- was significantly higher, directly after the SRT compared to all other timepoints (p<0.05). Plasma tCO2, HCO3- and Ca++ were significantly higher in treated than in control horses at multiple sampling timepoints after treatment/control administration (p<0.05). Serum insulin concentration, measured only pre and 30 min post treatment/control administration, was unaffected by treatment. Calcium propionate is an alkalizing agent in horses.

Dietary Fish Oil Does Not Alter Glucose Tolerance in Conscious Rats

We examined the effect of dietary fish oil (MaxEPA) and sunflower seed oil on glucose tolerance in male Wistar rats. Semipurified diets containing 100 g oil/kg diet were administered for 30 d. The fish oil diet contained 26 g (n-3) fatty acids, 16 g eicosapentaenoic acid and 10.4 g docosahexaenoic acid/kg diet. Phospholipids from liver, pancreas, and pancreatic islets were enriched in eicosapentaenoic and docosahexaenoic acids by the fish oil diet. In unfed pentobarbital-anesthetized rats, both basal plasma insulin concentration and insulin responses to intravenous glucose were significantly lower for fish oil-fed rats although glucose responses were similar; however, incremental excursions in plasma insulin over the basal concentrations did not differ. Intravenous glucose tolerance was also examined in conscious unfed rats under minimal restraint. Responses of plasma glucose and insulin were similar for fish oil- and sunflower oil-fed groups. Furthermore, in another experiment, intravenous glucose tolerance tests were similar for conscious rats provided with either 100 g fish oil or corn oil/kg nonpurified diet. Thus, glucose-induced insulin secretion is lower in rats fed fish oil than in rats fed sunflower oil, when tests are conducted in pentobarbital-anesthetized animals but not when tests are performed in conscious rats; there was no effect on plasma glucose in either anesthetized or nonanesthetized rats. Therefore, substitution of (n-3) for (n-6) polyunsaturated fatty acids in tissue phospholipids does not alter plasma glucose or insulin in conscious male Wistar rats.

Insight into synergetic effects of serum albumin and glucose on the biodegradation behavior of WE43 alloy in simulated body fluid

The biodegradation rate of Mg alloy medical devices, such as screws and plates for temporary bone fracture fixation or coronary angioplasty stents, is an increasingly important area of study. In vitro models of the corrosion behavior of these devices use revised simulated body fluid (m-SBF) based on a healthy individual’s blood chemistry. Therefore, model outputs have limited application to patients with altered blood plasma glucose or protein concentrations. This work studies the biodegradation behavior of Mg alloy WE43 in m-SBF modified with varying concentrations of glucose and bovine serum albumin (BSA) to (1) mimic a range of disease states and (2) determine the contributions of each biomolecule to corrosion. Measurements include the Mg ion release rate, electrolyte pH, the extent of hydrogen evolution (as a proxy for corrosion rate), surface morphology, and corrosion product composition and effects. BSA (0.1 g l–1) suppresses the rate of hydrogen evolution (about 30%) after 24 h and—to a lesser degree—Mg2+ release in both the presence and absence of glucose. This effect gets more pronounced with time, possibly due to BSA adsorption on the Mg surface. Electrochemical studies confirm that adding glucose (2 g l–1) to the solution containing BSA (0.1 g l–1) caused a decrease in corrosion resistance (by around 40%), and concomitant increase in the hydrogen evolution rate (from 10.32 to 11.04 mg cm–2 d–1) to levels far beyond the tolerance limits of live tissues.

The impact of ethnicity and intra-pancreatic fat on the postprandial metabolome response to whey protein in overweight Asian Chinese and European Caucasian women with prediabetes.

The "Thin on the Outside Fat on the Inside" TOFI_Asia study found Asian Chinese to be more susceptible to Type 2 Diabetes (T2D) compared to European Caucasians matched for gender and body mass index (BMI). This was influenced by degree of visceral adipose deposition and ectopic fat accumulation in key organs, including liver and pancreas, leading to altered fasting plasma glucose, insulin resistance, and differences in plasma lipid and metabolite profiles. It remains unclear how intra-pancreatic fat deposition (IPFD) impacts TOFI phenotype-related T2D risk factors associated with Asian Chinese. Cow's milk whey protein isolate (WPI) is an insulin secretagogue which can suppress hyperglycemia in prediabetes. In this dietary intervention, we used untargeted metabolomics to characterize the postprandial WPI response in 24 overweight women with prediabetes. Participants were classified by ethnicity (Asian Chinese, n=12; European Caucasian, n=12) and IPFD (low IPFD < 4.66%, n=10; high IPFD ≥ 4.66%, n=10). Using a cross-over design participants were randomized to consume three WPI beverages on separate occasions; 0g (water control), 12.5g (low protein, LP) and 50g (high protein, HP), consumed when fasted. An exclusion pipeline for isolating metabolites with temporal (T0-240mins) WPI responses was implemented, and a support vector machine-recursive feature elimination (SVM-RFE) algorithm was used to model relevant metabolites by ethnicity and IPFD classes. Metabolic network analysis identified glycine as a central hub in both ethnicity and IPFD WPI response networks. A depletion of glycine relative to WPI concentration was detected in Chinese and high IPFD participants independent of BMI. Urea cycle metabolites were highly represented among the ethnicity WPI metabolome model, implicating a dysregulation in ammonia and nitrogen metabolism among Chinese participants. Uric acid and purine synthesis pathways were enriched within the high IPFD cohort's WPI metabolome response, implicating adipogenesis and insulin resistance pathways. In conclusion, the discrimination of ethnicity from WPI metabolome profiles was a stronger prediction model than IPFD in overweight women with prediabetes. Each models' discriminatory metabolites enriched different metabolic pathways that help to further characterize prediabetes in Asian Chinese women and women with increased IPFD, independently.

Potential roles of oxidative stress and insulin resistance in diisononyl phthalate induced dyslipidemia and hepatosteatosis in BALB/c mice

Exposure to plastic-derived endocrine disrupting chemicals (EDCs) such as phthalates have become a source of concern to human health. Phthalates are applied industrially as plasticizers in the production of various plastic products. They have been reported for the various forms of toxic responses in both human and animal studies. Diisononyl phthalate (DiNP) was recently used to replace di(2-ethylhexyl) phthalate (DEHP) due to some toxicity concerns. However, recent evidences suggest that DiNP may disrupt the endocrine system, alter lipid metabolism and induce hepatic steatosis. Hence, this work was designed to probe the potential impacts of DiNP on oxidative stress biomarkers and insulin resistance as a possible link to dyslipidemia and development of hepatic steatosis. To achieve these, twenty seven (27) male BALB/c mice were distributed into three (3) experimental groups of nine (9) mice each. Group I was the control while mice in groups II and III were exposed to 20 and 200 mg/kg body weight, (bw) DiNP respectively orally (per os, p.o.) for 28 days. Thereafter, plasma insulin, glucose, plasma lipid levels as well as insulin resistance (IR) index were determined. The effects of DiNP on hepatic biomarker of inflammation (tumor necrosis factor alpha, TNF-α), oxidative stress (malondialdehyde, MDA), antioxidants (glutathione peroxidase, reduced glutathione and catalase) were also investigated in addition to liver histopathology. Data obtained show that DiNP especially at 200 mg/kg bw significantly (p < 0.05) alter plasma glucose and lipid profile and induced IR. Other responses observed at this dose level include significant inflammation, oxidative stress and hepatic fatty degeneration (as shown in hematoxylin and eosin stained liver sections). Current findings suggest that insulin resistance and oxidative stress may influence DiNP-induced dyslipidemia and hepatic steatosis in mice.

Moderate Intensity Exercise Causes a Shift in the Relative Importance of the Endothelium‐Dependent Relaxing Factors in Mesenteric Arteries of Male UC Davis Type‐2 Diabetes Mellitus (UCD‐T2DM) Rats

Over the past decade obesity and type 2 diabetes (T2D) have reached epidemic levels worldwide. Cardiovascular disease (CVD) is one of the leading causes of mortality and morbidity in diabetic patients. Regular aerobic exercise is a well-characterized lifestyle intervention that improves endothelial dysfunction, insulin resistance, and CVD risk in T2D. However, there are still debates regarding the duration and intensity of exercise required to ameliorate the deleterious metabolic perturbations in patients with T2D. The objective of this study was to investigate the effects of moderate intensity exercise (MIE) on vascular reactivity of mesenteric artery (MA) of male UC Davis Type-2 Diabetes Mellitus Rat (UCD-T2DM) model. Specifically, we examined whether there were changes in the relative contributions of endothelium-derived relaxing factors in modulating vascular reactivity of MA from exercise-trained compared with control sedentary UCD-T2DM rats. Age-matched male control and UCD-T2DM rats underwent forced treadmill exercise (E) or remained sedentary (S) for 8 weeks. Endothelium-dependent vasorelaxation (EDV) to acetylcholine (ACh, 10-8 to 10-5 M) were measured in precontracted MA before and after indomethacin (10µM), a cyclooxygenase (COX) inhibitor; followed by addition of L-NAME (200µM), a nitric oxide synthase (NOS) inhibitor; followed by combination of apamin (1 µM) and TRAM-34 (1 µM) (SKCa and IKCa blockers, respectively). The diabetic exercise trained (DE) rats exhibited decreased visceral adiposity and plasma triglyceride levels compared with the diabetic sedentary (DS) group. However, MIE did not alter plasma glucose or insulin concentrations in either nondiabetic or diabetic UCD-T2DM Rats. Both sensitivity and maximal responses (Emax) to ACh were significantly reduced in MA from DS rats compared with those in control sedentary (CS). MIE improved the Emax to ACh only in MA of DE group. Inhibition of COX enhanced Emax to ACh in DS arteries suggesting the elevation of contractile COX metabolites in the DS group. The addition of L-NAME resulted in a reduction in ACh relaxation of arteries from both CS and DS rats, however the effect was more prominent in DS group, suggesting the contribution of NO was enhanced (or endothelium-dependent hyperpolarizing factor (EDHF)-type relaxation was diminished) in DS arteries. Remarkably, MIE reversed the loss of EDHF-type relaxation in UCD-T2DM Rats. Unlike in the DS group, inhibition of COX had no effect on ACh response in MA of the DE group, suggesting that MIE may cause a shift from contractile COX to NO and EDHF-type relaxation in UCD-T2DM Rats. In conclusion, we provide the first evidence for a positive impact of moderate exercise on mesenteric arterial function in male UCD-T2DM Rats, likely mediated by a contribution of EDHF-type (NO and prostanoid-independent) responses.

Different Gestational Diabetes Phenotypes: Which Insulin Regimen Fits Better?

ObjectiveMaternal characteristics and OGTT values of pregnancies complicated by gestational diabetes mellitus (GDM) were evaluated according to treatment strategies. The goal was to identify different maternal phenotypes in order to predict the appropriate treatment strategy.MethodsWe conducted a retrospective study among 1,974 pregnant women followed up for GDM in a tertiary referral hospital for high-risk pregnancies (Careggi University Hospital, Florence, Italy) from 2013 to 2018. We compared nutritional therapy (NT) alone (n = 962) versus NT and insulin analogues (n = 1,012) group. Then, we focused on different insulin analogues groups: long acting (D), rapid acting (R), both D and R. We compared maternal characteristics of the three groups, detecting which factors may predict the use of rapid or long-acting insulin analogue alone versus combined therapy.ResultsAmong women included in the analysis, 51.3% of them needed insulin therapy for glycemic control: 61.8% D, 28.3% combined D and R, and 9.9% R alone. Age >35 years, pre-pregnancy BMI >30, family history of diabetes, previous GDM, altered fasting plasma glucose (FPG), hypothyroidism, and assisted reproductive technologies (ART) were identified as maternal variables significantly associated with the need of insulin therapy. Altered 1-h and 2-h glucose plasma glucose level at OGTT, age >35 years, and previous GDM were found as independent predicting factors for the use of combined therapy with rapid and long acting analogues for glycemic control. On the contrary, pre-pregnancy BMI <25 and normal fasting plasma glucose values at OGTT were found to be significantly associated to the use of rapid insulin analogue only.ConclusionA number of maternal and metabolic variables may be identified at the diagnosis of GDM, in order to identify different GDM phenotypes requiring a personalized treatment for glycemic control.

LXRα/β Antagonism Protects against Lipid Accumulation in the Liver but Increases Plasma Cholesterol in Rhesus Macaques.

Nonalcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver and associates with obesity, hyperlipidemia, and insulin resistance. NAFLD could lead to nonalcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis, and even cancers. The development of therapy for NAFLD has been proven difficult. Emerging evidence suggests that liver X receptor (LXR) antagonist is a potential treatment for fatty liver disease. However, concerns about the cholesterol-increasing effects make it questionable for the development of LXR antagonists. Here, the overweight monkeys were fed with LXRβ-selective antagonist sophoricoside or LXRα/β dual-antagonist morin for 3 months. The morphology of punctured liver tissues was examined by H&E staining. The liver, heart, and kidney damage indices were analyzed using plasma. The blood index was assayed using complete blood samples. We show that LXRβ-selective antagonist sophoricoside and LXRα/β dual-antagonist morin alleviated lipid accumulation in the liver in overweight monkeys. The compounds resulted in higher plasma TC or LDL-c contents, increased white blood cell and lymphocyte count, and decreased neutrophile granulocyte count in the monkeys. The compounds did not alter plasma glucose, apolipoprotein A (ApoA), ApoB, ApoE, lipoprotein (a) (LPA), nonesterified fatty acid (NEFA), aspartate transaminases (AST), creatinine (CREA), urea nitrogen (UN), and creatine kinase (CK) levels. Our data suggest that LXRβ-selective and LXRα/β dual antagonism may lead to hypercholesterolemia in nonhuman primates, which calls into question the development of LXR antagonist as a therapy for NAFLD.

A four-week high fat diet does not alter plasma glucose or metabolic physiology in wild-caught mourning doves (Zenaida macroura)

The aim of this study was to determine the metabolic effects of a four-week 60% high-fat (HF) diet on mourning doves. Plasma glucose concentrations are, on average, 1.5–2 times higher in birds than in mammals of similar body mass, but birds have innate mechanisms that protect them from high blood glucose-associated pathologies normally developed in mammals. Elucidating these mechanisms may help develop therapeutics for treatment of human diabetes-related complications. A high fat (HF) diet is commonly used in rodents to investigate metabolic disease. We hypothesized that this diet in doves would elevate plasma glucose and alter metabolic physiology compared to the control (CON) diet. Following the four-week long diets, doves were euthanized, and we collected blood, liver, pectoralis muscles, and kidney samples. Contrary to the rodent-models, HF-fed birds did not have increased plasma glucose concentrations relative to CON-fed birds. Metabolomic analyses revealed no group differences in plasma, liver, pectoralis muscle, or kidney metabolites (FDR q-value>0.05 for all). Principal component analysis score plots of metabolites showed no separation between groups, and pathway analyses revealed no significantly altered metabolic pathways between groups (191 pathways across tissues, FDR q-value>0.05). Body mass, plasma uric acid, glucose, and insulin as well as liver and pectoralis muscle glycogen and triglycerides did not differ between groups (p > 0.05 for all). In conclusion, a four-week long high fat diet did not alter plasma glucose concentrations or metabolic physiology in mourning doves, indicating that these birds have mechanisms that allow them to avoid high fat diet-induced pathologies seen in mammals.

GH directly inhibits steatosis and liver injury in a sex-dependent and IGF1-independent manner.

A reduction in hepatocyte growth hormone (GH)-signaling promotes non-alcoholic fatty liver disease (NAFLD). However, debate remains as to the relative contribution of the direct effects of GH on hepatocyte function vs indirect effects, via alterations in insulin-like growth factor 1 (IGF1). To isolate the role of hepatocyte GH receptor (GHR) signaling, independent of changes in IGF1, mice with adult-onset, hepatocyte-specific GHR knockdown (aHepGHRkd) were treated with a vector expressing rat IGF1 targeted specifically to hepatocytes. Compared to GHR-intact mice, aHepGHRkd reduced circulating IGF1 and elevated GH. In male aHepGHRkd, the shift in IGF1/GH did not alter plasma glucose or non-esterified fatty acids (NEFA), but was associated with increased insulin, enhanced systemic lipid oxidation and reduced white adipose tissue (WAT) mass. Livers of male aHepGHRkd exhibited steatosis associated with increased de novo lipogenesis, hepatocyte ballooning and inflammation. In female aHepGHRkd, hepatic GHR protein levels were not detectable, but moderate levels of IGF1 were maintained, with minimal alterations in systemic metabolism and no evidence of steatosis. Reconstitution of hepatocyte IGF1 in male aHepGHRkd lowered GH and normalized insulin, whole body lipid utilization and WAT mass. However, IGF1 reconstitution did not reduce steatosis or eliminate liver injury. RNAseq analysis showed IGF1 reconstitution did not impact aHepGHRkd-induced changes in liver gene expression, despite changes in systemic metabolism. These results demonstrate the impact of aHepGHRkd is sexually dimorphic and the steatosis and liver injury observed in male aHepGHRkd mice is autonomous of IGF1, suggesting GH acts directly on the adult hepatocyte to control NAFLD progression.

Dietary protein intake and obesity-associated cardiometabolic function.

High-protein intake is commonly recommended to help people manage body weight. However, high-protein intake could have adverse health consequences. Here we review the latest findings concerning the effect of high-protein intake on cardiometabolic health. Calorie-reduced, high-protein, low-carbohydrate diets lower plasma glucose in people with type 2 diabetes (T2D). However, when carbohydrate intake is not markedly reduced, high-protein intake often does not alter plasma glucose and increases insulin and glucagon concentrations, which are risk factors for T2D and ischemic heart disease. High-protein intake does not alter plasma triglyceride and cholesterol concentrations but promotes atherogenesis in animal models. The effect of high-protein intake on liver fat remains unclear. In population studies, high-protein intake is associated with increased risk for T2D, nonalcoholic fatty liver disease, and possibly cardiovascular diseases. The relationship between protein intake and cardiometabolic health is complex and influenced by concomitant changes in body weight and overall diet composition. Although a high-protein, low-carbohydrate, reduced-energy diet can have beneficial effects on body weight and plasma glucose, habitual high-protein intake, without marked carbohydrate and energy restriction, is associated with increased cardiometabolic disease risk, presumably mediated by the changes in the hormonal milieu after high-protein intake.

Impact of caudal hindbrain glycogen metabolism on A2 noradrenergic neuron AMPK activation and ventromedial hypothalamic nucleus norepinephrine activity and glucoregulatory neurotransmitter marker protein expression

The brain glycogen reserve is a source of oxidizable substrate fuel. Lactoprivic-sensitive hindbrain A2 noradrenergic neurons provide crucial metabolic-sensory input to downstream hypothalamic glucose-regulatory structures. Current research examined whether hindbrain glycogen fuel supply impacts A2 energy stability and governance of ventromedial hypothalamic nucleus (VMN) metabolic transmitter signaling. Male rats were injected into the caudal fourth ventricle (CV4) with the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) prior to continuous intra-CV4 infusion of L-lactate or vehicle. Lactate reversed DAB suppression of A2 neuron AMPK protein and up-regulated phosphoAMPK profiles. A2 dopamine-β-hydroxylase expression was refractory to DAB, but elevated by DAB/lactate. Lactate normalized A2 estrogen receptor-alpha and GPER proteins and up-regulated estrogen receptor-beta levels in DAB-treated rats. VMN norepinephrine content was decreased by DAB, but partially restored by lactate. DAB caused lactate-reversible or -irreversible augmentation of VMN glycogen phosphorylase-brain (GPbb) and -muscle type (GPmm) variant profiles, and correspondingly up- or down-regulated VMN protein markers of glucose-stimulatory nitrergic and glucose-inhibitory γ-aminobutyric acid transmission. DAB did not alter plasma glucose, but suppressed or elevated circulating glucagon and corticosterone in that order. Results show that diminished hindbrain glycogen breakdown is communicated to the VMN, in part by NE signaling, to up-regulate VMN glycogen breakdown and trigger neurochemical signaling of energy imbalance in that site. DAB effects on GPmm, VMN glycogen content, and counter-regulatory hormone secretion were unabated by lactate infusion, suggesting that aside from substrate fuel provision rate, additional indicators of glycogen metabolism such as turnover rate may be monitored in the hindbrain.

A four-week white bread diet does not alter plasma glucose concentrations, metabolic or vascular physiology in mourning doves, Zenaida macroura

Birds are an enigma: their plasma glucose concentration is 1.5–2 times higher than similar-sized mammals, yet they do not normally exhibit symptoms of diabetes. We hypothesized that feeding adult mourning doves a refined carbohydrate diet (white bread: WB) for four weeks would raise plasma glucose concentrations and alter metabolic pathways and endothelial function when compared to birds receiving a nutritionally-balanced diet (bird seeds: SD). Following the four-week long diets, birds were euthanized, and cardiac blood, liver, and pectoralis muscles were collected for metabolomics analyses and biochemical assays. Cranial tibial arteries were dissected to measure acetylcholine-mediated vasodilation. Contrary to the hypothesis, WB-fed birds did not have increased plasma glucose concentrations. Principle component analysis score plots suggest minimal differences between groups. However, we identified 15 changes in individual metabolite concentrations between diet groups that, although not statistically significant, are highly predictive (area under receive operating curve, AUROC>0.90; number of highly predictive metabolites: 5 of 123 in plasma, 4 of 92 in liver, and 6 of 92 in pectoralis muscle). Moreover, pathway analyses revealed no significantly altered metabolic pathways between groups. Biochemical assays revealed no significant group differences in plasma uric acid and insulin, or pectoralis muscle glycogen concentrations. However, hepatic glycogen concentration was 2.12-fold higher in the WB group than in control doves (p = .015). Diet type did not influence vasodilation. In conclusion, a four-week long white bread diet increased liver glycogen but did not alter plasma glucose concentrations, metabolic or vascular physiology in mourning doves.

Effect of ipragliflozin, an SGLT2 inhibitor, on cardiac histopathological changes in a non-diabetic rat model of cardiomyopathy

AimsWe investigated the effect of the selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin on cardiac dysfunction and histopathology in a non-diabetic rat model of cardiomyopathy. Main methodsIpragliflozin was mixed with chow (0.01%, w/w) and administered to male DahlS.Z-Leprfa/Leprfa (DS/obese) rats for 8 weeks. Male DahlS.Z-Lepr+/Lepr+ (DS/lean) rats of the same age were used as controls. Systolic blood pressure (SBP) and heart rate (HR) were measured every 4 weeks. After 8 weeks of treatment, echocardiography and histopathological examinations were performed. Further, the effect of ipragliflozin on blood and urine parameters were investigated. Key findingsIn the DS/obese rats, ipragliflozin delayed the age-related increase in SBP without affecting HR, reduced left ventricular (LV) mass and intraventricular septal thickness in echocardiography, and ameliorated hypertrophy of cardiomyocytes and LV fibrosis in histopathological examination. Although ipragliflozin significantly increased both urine volume and urinary glucose excretion in DS/obese rats, it did not alter plasma glucose levels. SignificanceIpragliflozin prevented LV hypertrophy and fibrosis in non-diabetic DS/obese rats without affecting plasma glucose levels. These findings suggest that SGLT2 inhibitors have a cardio-protective effect in non-diabetic patients with cardiomyopathy.

Effects of sodium salicylate on glucose kinetics and insulin signaling in postpartum dairy cows

Low-grade inflammation has been implicated as a contributor to metabolic disease during the transition to lactation. In previous work, administration of sodium salicylate (SS) for 7 d led to hypoglycemia in mature dairy cows in early lactation. The purpose of this study was to identify the mode of action underlying this response to SS. Twenty mature (parity 3) cows were assigned alternately at time of calving to either control or SS treatments; the control received a molasses placebo in drinking water, whereas SS received 2.3 g/L of SS with the molasses carrier in drinking water for 7 d after parturition. Blood samples were collected daily. A glucose turnover assay was performed on d 7, followed by liver, muscle, and adipose tissue biopsies. There were no treatment effects on intake of dry matter or water. Tumor necrosis factor α mRNA abundance tended to be decreased by SS in adipose tissue but not in muscle or liver, and plasma haptoglobin and adiponectin concentrations were not altered by treatment. Treatment did not significantly alter plasma glucose or insulin concentrations, but plasma glucagon concentration tended to be increased by SS and the insulin:glucagon molar ratio was significantly decreased. Cows on SS had a tendency for a 25% decrease in glucose turnover rate compared with control cows. However, there were no differences in transcript abundance of pyruvate carboxylase (PC) or glucose-6-phosphatase (G6PC) in liver or of glucose transporter 4 (GLUT4) in any of the tissues. Finally, SS did not alter insulin receptor substrate-1 phosphorylation in muscle or adipose, but tended to increase phosphorylation of AMP-activated protein kinase and decrease protein kinase B phosphorylation in adipose tissue. These findings may be explained by enhanced hepatic insulin sensitivity leading to posttranscriptional suppression of gluconeogenesis and adaptive responses to decreased glucose supply in the pancreas and adipose tissue.

Role of Melanocortin‐4 Receptor Activation in Hypertension Induced by Chronic Intermittent Hypoxia

Obesity is often associated with chronic intermittent hypoxia (CIH), increased sympathetic nervous system (SNS) activity and hypertension (HT). We previously demonstrated that melanocortin 4 receptors (MC4R) play a key role in regulating blood pressure (BP) in obesity and other conditions associated with increased SNS activity. In this study we examined if activation of CNS MC4R contributes to CIH‐induced HT. Wild‐type (WT, n=6), obese MC4R knockout (MC4R‐KO, n=5) and lean pair‐weighted (PW) MC4R‐KO (n=5) rats were instrumented with telemetry probes for measurement of mean arterial pressure (MAP) and heart rate (HR) 24‐hrs/day. The rats were exposed to CIH (8 hrs/day from 8:00–16:00 hours for 7 consecutive days). CIH significantly reduced food intake in obese MC4R‐KO rats by 50% leading to net cumulative reduction of −108±13 g compared to a −33±3 g cumulative food intake reduction in control WT rats. Food intake was kept at baseline values and was not altered by CIH in PW‐MC4RKO rats. Body weight was reduced by 7.5, 12.0 and 3.5 % in obese MC4R‐KO, WT and lean PW‐MC4R‐KO rats, respectively. CIH did not significantly alter plasma glucose concentration in MC4R‐KO or WT rats. However, CIH reduced plasma leptin concentration in obese MC4R‐KO rats (12±2 vs. 18±2 ng/mL during control period) while increasing leptin concentration in WT rats (1.8±0.5 vs. 0.9±0.1 ng/mL). CIH reduced fasting insulin concentration in WT rats (7±2 vs. 15±3 mU/mL) but did not alter insulin in MC4R‐KO rats (67±7 vs. 71±14 mU/mL). Baseline MAP was higher in obese and lean PW‐MC4R‐KO compared to WT rats (114±4, 112±2 and 107±2 mmHg), and CIH significantly increased MAP by approximately 11, 6 and 9 mmHg, respectively. Baseline HR was not different in obese MC4R‐KO and control rats (314±3 and 321±5 bpm), but lean PW‐MC4R‐KO had significantly lower HR (291±8 bpm). These results suggest that obesity and CNS melanocortin system may interact in complex ways to elevate BP during CIH. (NHLBI‐PO1HL51971, NIGMS P20GM104357)Support or Funding InformationDepartment of Physiology and Biophysics and Mississippi Center for Obesity Research. University of Mississippi Medical Center, Jackson, MS.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effects of Oleacein on High-Fat Diet-Dependent Steatosis, Weight Gain, and Insulin Resistance in Mice.

Many reports indicate that the protective action of nutraceuticals in the Mediterranean diet, against metabolic and cardiovascular diseases, can be attributed to the action of polyphenolic components of extra-virgin olive oil (EVOO). Here, we evaluated the protective effects of oleacein, one of the most abundant secoiridoids in EVOO, on the damages/metabolic alterations caused by high-fat diet (HFD) in male C57BL/6JolaHsd mice. After 5 weeks of treatment with 20 mg/kg of oleacein, body weight, glycemia, insulinemia, serum lipids, and histologic examination of liver tissue indicated a protective action of oleacein against abdominal fat accumulation, weight gain, and liver steatosis, with improvement of insulin-dependent glucose and lipid metabolism. Both serum parameters and hepatic histologic examination were altered in mice fed with HFD. By contrast, in the animals that received oleacein, plasma glucose, cholesterol and triglyceride serum levels, and liver histology were similar to controls fed with normocaloric diet. In addition, protein levels of FAS, SREBP-1, and phospho-ERK in liver were positively modulated by oleacein, indicating an improvement in liver insulin sensitivity. In a group of obese mice, treatment with oleacein determined a light, but still significant reduction of the increase in body weight, mainly due to lesser liver steatosis enlargement, associated with reduced levels of SREBP-1 and phospho-ERK and lower levels of total serum cholesterol; in these animals, altered plasma glucose and triglyceride serum levels were not reverted by oleacein. These results indicate that HFD-related hepatic insulin resistance may be partially prevented by oral administration of oleacein, suggesting a protective role of this nutraceutical against diet-dependent metabolic alterations. Additional studies are necessary to check whether oleacein can be used as an adjuvant to improve insulin sensitivity in humans.

Acute effect of Clitoria ternatea flower beverage on glycemic response and antioxidant capacity in healthy subjects: a randomized crossover trial

BackgroundClitoria ternatea L., a natural food-colorant containing anthocyanin, demonstrated antioxidant and antihyperglycemic activity. The aim of this study was to determine the effects of Clitoria ternatea flower extract (CTE) on postprandial plasma glycemia response and antioxidant status in healthy men.MethodsIn a randomized, crossover study, 15 healthy men (ages 22.53 ± 0.30 years; with body mass index of 21.57 ± 0.54 kg/m2) consumed five beverages: (1) 50 g sucrose in 400 mL water; (2) 1 g CTE in 400 mL of water; (3) 2 g CTE in 400 mL of water; (4) 50 g sucrose and 1 g CTE in 400 mL of water; and (5) 50 g sucrose and 2 g CTE in 400 mL of water. Incremental postprandial plasma glucose, insulin, uric acid, antioxidant capacities and lipid peroxidation were measured during 3 h of administration.ResultsAfter 30 min ingestion, the postprandial plasma glucose and insulin levels were suppressed when consuming sucrose plus 1 g and 2 g CTE. In addition, consumption of CTE alone did not alter plasma glucose and insulin concentration in the fasting state. The significant increase in plasma antioxidant capacity (ferric reducing ability of plasma (FRAP), oxygen radical absorbance capacity (ORAC), trolox equivalent antioxidant capacity (TEAC), and protein thiol) and the decrease in malondialdehyde (MDA) level were observed in the subjects who received 1 g and 2 g CTE. Furthermore, consumption of CTE protected sucrose-induced reduction in ORAC and TEAC and increase in plasma MDA.ConclusionsThese findings suggest that an acute ingestion of CTE increases plasma antioxidant capacity without hypoglycemia in the fasting state. It also improves postprandial glucose, insulin and antioxidant status when consumed with sucrose.Trial registrationThai Clinical Trials Registry: TCTR20170609003. Registered 09 September 2017.‘retrospectively registered’.

Influence of green tea consumption on cigarette smoking-induced biochemical changes in plasma and blood

Summary Cigarette smoking causes numerous adverse biochemical changes in plasma and blood leading to ill health effects for which therapeutic approaches are sought. The present study investigates the effect of green tea consumption on confirmed cigarette smokers. Blood samples were collected from 120 selected human male volunteers categorized in to four groups viz., controls, smokers, control volunteers consuming green tea with no habit of smoking and smokers consuming green tea were analysed. Results showed that altered plasma glucose, HbA1c, hemoglobin, hematocrit, total cholesterol, lipoprotein patterns (HDL, LDL, VLDL) and lipid peroxidation along with vitamins (vitamin-D, vitamin-B12, vitamin-C) and minerals (iron, total iron binding capacity, calcium, sodium, potassium, phosphorous, chloride) followed by the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (γGT) and alkaline phosphatase (ALP). Furthermore, phytochemical analysis of green tea confirmed the presence of phenols, flavonoids and tannins. Antioxidants and free radical scavenging effects of green tea were assessed using 2, 2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS+) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH+). Results of this study clearly demonstrated that the adverse changes observed in the above biochemical parameters in smokers were reversed upon green tea supplementation which can be attributed to the phytoconstituents present in green tea. In conclusion, both in vivo and in vitro studies revealed that phytocompounds present in green tea are able to scavenge free radicals and by there offers protection against smoking induced biochemical alterations.

Association of General and Abdominal Obesity With Hypertension, Dyslipidemia and Prediabetes in the PREDAPS Study

Introduction and objectivesSome anthropometric measurements show a greater capacity than others to identify the presence of cardiovascular risk factors. This study estimated the magnitude of the association of different anthropometric indicators of obesity with hypertension, dyslipidemia, and prediabetes (altered fasting plasma glucose and/or glycosylated hemoglobin). MethodsCross-sectional analysis of information collected from 2022 participants in the PREDAPS study (baseline phase). General obesity was defined as body mass index ≥ 30kg/m2 and abdominal obesity was defined with 2 criteria: a) waist circumference (WC) ≥ 102cm in men/WC ≥ 88cm in women, and b) waist-height ratio (WHtR) ≥ 0.55. The magnitude of the association was estimated by logistic regression. ResultsHypertension showed the strongest association with general obesity in women (OR, 3.01; 95%CI, 2.24-4.04) and with abdominal obesity based on the WHtR criterion in men (OR, 3.65; 95%CI, 2.66-5.01). Hypertriglyceridemia and low levels of high-density lipoprotein cholesterol showed the strongest association with abdominal obesity based on the WHtR criterion in women (OR, 2.49; 95%CI, 1.68-3.67 and OR, 2.70; 95%CI, 1.89-3.86) and with general obesity in men (OR, 2.06; 95%CI, 1.56-2.73 and OR, 1.68; 95%CI, 1.21-2.33). Prediabetes showed the strongest association with abdominal obesity based on the WHtR criterion in women (OR, 2.48; 95%CI, 1.85-3.33) and with abdominal obesity based on the WC criterion in men (OR, 2.33; 95%CI, 1.75-3.08). ConclusionsAbdominal obesity indicators showed the strongest association with the presence of prediabetes. The association of anthropometric indicators with hypertension and dyslipidemia showed heterogeneous results.