Changes In Plasma Glucose Levels Research Articles

Fructose-induced FGF21 secretion does not activate brown adipose tissue in Japanese young men: randomized cross-over and randomized controlled trials

BackgroundHuman brown adipose tissue (BAT) activity is associated with lower body fatness and favorable glucose metabolism. Previous studies reported that oral fructose loading induces postprandial fibroblast growth factor 21 (FGF21) secretion. FGF21 is a known inducer of adipose tissue thermogenesis; however, the effects of diet-induced FGF21 secretion on BAT thermogenesis remain to be elucidated.MethodsThe effects of both single load and daily consumption of fructose on BAT activity were examined using a randomized cross-over trial and a 2-week randomized controlled trial (RCT), respectively. In the cross-over trial, 15 young men consumed a single dose of fructose solution or water and then consumed the other on a subsequent day. The RCT enrolled 22 young men, and the participants were allocated to a group that consumed fructose and a group that consumed water daily for 2 weeks. BAT activity was analyzed using thermography with cold exposure. Plasma FGF21 level was determined by enzyme-linked immunosorbent assay.ResultsIn the cross-over single-load trial, plasma FGF21 levels were significantly increased at 2 h after oral fructose load (p < 0.01); however, there was no significant difference in BAT activity between the fructose load and drinking water. The 2-week RCT revealed that both plasma FGF21 levels and BAT activity were not significantly increased by daily fructose consumption compared to water. Correlation analyses revealed that BAT activity at the baseline and the final measurements were strongly and positively associated with the RCT (r = 0.869, p < 0.001). Changes in BAT activity were significantly and negatively correlated with changes in plasma glucose levels during the 2-week intervention (r = − 0.497, p = 0.022).ConclusionsOral fructose load induces a temporary increase in circulating FGF21 levels; however, this does not activate BAT thermogenesis in healthy young men. Further studies are needed to elucidate the effect of endogenous FGF21 on physiological function.Trial registrationThis study is registered with the University Hospital Medical Information Network in Japan (number 000051761, registered 1 August 2023, retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000052680).

Insulin Secretion in Extended Mixed-Meal Tolerance Test in the Context of the Four Phases of Digestion

Background: A sequential response of insulin secretion is likely to follow the sequential pattern of digestion to optimize the effect of insulin and other counter regulatory peptides on the target tissues to maintain optimum insulin signaling pathway activation. Therefore, it is likely to relate insulin secretory response to the corresponding phase of digestion. Patients and methods: Plasma glucose, insulin and glucagon levels of three groups, each comprises of 10 persons. Group “N” for normal, group “P” for pre-diabetic and group “D” for type 2 diabetes individuals. Fluctuations in insulin secretion, in relation to changes of plasma glucose levels throughout the four phases of digestion will be traced, changes in glucagon levels will be also evaluated. Results: Early in the gastric-filling phase insulin was decreasing while glucose was rising, whereas, early in the gastric-emptying phase, insulin was rising while glucose was decreasing. Statistical significance of glucagon changes was higher than that of insulin between groups. Conclusion: Factors, which regulate insulin secretion during the gastric-filling phase, may differ than those during the gastric emptying-phase. Insulin/Glucagon ratio, is more contributed, than insulin alone, to the metabolic abnormalities associated with diabetes. It is more informative to consider insulin secretion in relation to the corresponding phase of digestion. Therefore, a four- phase cycle of insulin secretion may be suggested.

Associations between per- and polyfluoroalkyl substances (PFAS) and diabetes in two population-based cohort studies from Sweden

BackgroundPer- and polyfluoroalkyl substances (PFAS) have been suggested to contribute to the development of metabolic diseases such as obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). However, evidence from epidemiological studies remain divergent. The aim of the present study was to evaluate associations between PFAS exposure and prevalent diabetes in a cross-sectional analysis and fasting glucose in a longitudinal analysis.MethodsIn 2373 subjects aged 45–75 years from the EpiHealth study, three PFAS; perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were analyzed in plasma together with information on prevalent diabetes. Participants in the PIVUS study (n = 1016 at baseline, all aged 70 years) were followed over 10 years regarding changes in plasma levels of six PFAS; PFHxS, PFOA, PFOS, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), and changes in plasma levels of fasting glucose.ResultsIn the EpiHealth study, no overall associations could be observed between the levels of PFOA, PFOS or PFHxS and prevalent diabetes. However, there was a significant sex-interaction for PFOA (p = 0.02), and an inverse association could be seen between PFOA (on a SD-scale) and prevalent diabetes in women only (OR: 0.71, 95% CI: 0.52, 0.96, p-value: 0.02). This association showed a non-monotonic dose-response curve. In the PIVUS study, inverse relationships could be observed between the changes in levels (ln-transformed) of PFOA and PFUnDA vs the change in fasting glucose levels (ln-transformed) over 10 years (p = 0.04 and p = 0.02, respectively). As in EpiHealth, these inverse associations were significant only in women (PFOA: β: −0.03, p = 0.02, PFUnDA: β: −0.03, p = 0.03).ImpactExposure to per- and polyfluoroalkyl substances (PFAS) has been linked to unfavorable human health, including metabolic disorders such as obesity, diabetes and non-alcoholic fatty liver disease. However, results from in vivo, in vitro and epidemiological studies are incoherent. The aim of the present study was therefore to investigate associations between PFAS and diabetes in a cross-sectional study and glucose levels in a longitudinal study. Results show inverse associations in women only. Results also display non-monotonic dose response curves (i.e., that only low levels of PFOA are related to higher probability of prevalent diabetes). This suggests that sex differences and complex molecular mechanisms may underlie the observed findings. A better understanding of the factors and molecular mechanisms contributing to such differences is recognized as an important direction for future research.ConclusionsPFOA was found to be inversely related to both prevalent diabetes and changes in plasma glucose levels among women only. Thus, our findings suggest there are sex differences in the inverse relationship of PFOA and type 2 diabetes and glucose levels.

Reproducibility of plasma glucose responses to moderate-intensity exercise in individuals with type 1 diabetes.

To examine the within-person variability in plasma glucose responses to moderate-intensity morning exercise in young individuals with type 1 diabetes after overnight fasting and under basal insulin conditions. In this pilot study, eight participants completed 40 min of moderate-intensity exercise at 60% V̇O2 peak on three separate days. The within-person standard deviation (SDw) in plasma glucose response was analysed both during and 1 h after exercise using the two visits per participant most closely matched by pre-exercise plasma glucose level. When the two closest matched visits per individual were included for analysis, mean (±SD) change in plasma glucose level was -1.8± 1.1 mmoL/L during exercise and -0.6± 1.0 mmoL/L during recovery, with the SDw of these changes being 0.5 mmol (95% CI 0.2, 0.8) during exercise and 0.8 mmoL/L (95% CI 0.4, 1.3) during recovery. The median intra-individual difference in plasma glucose level change was 0.3 mmoL/L [IQR 0.1, 0.7] during exercise and 0.8 mmoL/L [IQR 0.4, 1.0] during recovery. Within-person plasma glucose responses to moderate-intensity exercise may be reproducible under fasting and basal insulin conditions and similar pre-exercise plasma glucose levels. This finding may assist the design of future studies investigating both the reproducibility of glycaemic responses to exercise and blood glucose management for individuals with type 1 diabetes.

Impact of healthy lifestyle on the risk of type 2 diabetes mellitus in southwest China: A prospective cohort study

To explore the influence of nine healthy lifestyle factors on the risk of type 2 diabetes mellitus in adults in Guizhou, China. Data were obtained from a large population-based prospective cohort study in Guizhou Province, China. A total of 7,319 participants aged ≥18 years without diabetes at baseline were included in this study and were followed up from 2016 to 2020. A healthy lifestyle score was calculated based on the number of healthy lifestyle factors. During an average of 7.1 person-years of follow-up, 764 participants were diagnosed with type 2 diabetes mellitus. Compared with those of participants who scored 0-3 for a healthy lifestyle, the hazard ratios (95% confidence intervals) of those who scored 4, 5, 6, and ≥7 were 0.676 (0.523-0.874), 0.599 (0.464-0.773), 0.512 (0.390-0.673), and 0.393 (0.282-0.550), respectively, showing a gradual downward trend (P for trend <0.01). More importantly, they had lower fasting and 2 h post-load plasma glucose levels and fewer changes in plasma glucose levels during follow-up. If ≥7 healthy lifestyle factors were maintained, 33.8% of incident diabetes cases could have been prevented. Never smoking was the strongest protective factor against type 2 diabetes mellitus. A healthy lifestyle can effectively decrease plasma glucose levels and reduce the incidence of type 2 diabetes mellitus in adults in Guizhou, China. In addition, not smoking may be an effective way to prevent type 2 diabetes mellitus.

Electroacupuncture at Bilateral ST36 Acupoints: Inducing the Hypoglycemic Effect through Enhancing Insulin Signal Proteins in a Streptozotocin-Induced Rat Model during Isoflurane Anesthesia.

In rats with 2-deoxy-2-(3-(methyl-3-nitrosoureido)-d-glucopyranose streptozotocin- (STZ-) induced insulin-dependent diabetes (IDDM), continuous 15 Hz electrical stimulation at bilateral ST36 acupoints for 30 and 60 minutes has been shown to prevent hyperglycemia. We hypothesized that the mechanism of action in STZ-induced IDDM rats is that electrical stimulation at bilateral ST36 acupoints is effective in improving insulin receptor substrate type 1 (IRS-1) and glucose transporter type 4 (GLUT4) protein expressions associated with counteracting both plasma glucose and free fatty acid (FFA) levels during isoflurane anesthesia. In this study, twenty-six healthy male Wistar rats, weighing 250–350 g and aged 8–10 weeks were tested. Rats in the experimental electroacupuncture (EA) group (n = 13) received 15 Hz electrical stimulation at bilateral ST 36 acupoints for 30 and 60 minutes. Rats in the control group (n = 13) were handled but not subjected to the stimulation treatment. In both IDDM and normal Wistar rats, we observed a negative change in plasma glucose levels when rats were given the EA treatment, but a positive change in plasma glucose without EA treatment relative to baseline. Within the IDDM group, a negative change in FFA levels was observed when rats were given the EA treatment, while a positive change in the FFA level was shown without the EA treatment. In the expressed protein signals, we found a significant elevation in both GLUT4 and IRS-1 proteins in the IDDM group treated by EA. Moreover, we found a significant mean difference between GLUT4 and IRS-1 protein expression levels relative to β-actin. Our findings suggested that EA at bilateral ST36 acupoints could serve as an effective strategy for lowering plasma glucose by decreasing free fatty acid levels and improving the expression of IRS-1 and GLUT4 proteins in a STZ-IDDM rat model during isoflurane anesthesia.

Dynamic alterations in the central glutamatergic status following food and glucose intake: in vivo multimodal assessments in humans and animal models

Fluctuations of neuronal activities in the brain may underlie relatively slow components of neurofunctional alterations, which can be modulated by food intake and related systemic metabolic statuses. Glutamatergic neurotransmission plays a major role in the regulation of excitatory tones in the central nervous system, although just how dietary elements contribute to the tuning of this system remains elusive. Here, we provide the first demonstration by bimodal positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) that metabotropic glutamate receptor subtype 5 (mGluR5) ligand binding and glutamate levels in human brains are dynamically altered in a manner dependent on food intake and consequent changes in plasma glucose levels. The brain-wide modulations of central mGluR5 ligand binding and glutamate levels and profound neuronal activations following systemic glucose administration were further proven by PET, MRS, and intravital two-photon microscopy, respectively, in living rodents. The present findings consistently support the notion that food-associated glucose intake is mechanistically linked to glutamatergic tones in the brain, which are translationally accessible in vivo by bimodal PET and MRS measurements in both clinical and non-clinical settings.

Role of central kisspeptin and RFRP-3 in energy metabolism in the male Wistar rat.

Kisspeptin (Kp) and (Arg)(Phe) related peptide 3 (RFRP‐3) are two RF‐amides acting in the hypothalamus to control reproduction. In the past 10 years, it has become clear that, apart from their role in reproductive physiology, both neuropeptides are also involved in the control of food intake, as well as glucose and energy metabolism. To investigate further the neural mechanisms responsible for these metabolic actions, we assessed the effect of acute i.c.v. administration of Kp or RFRP‐3 in ad lib. fed male Wistar rats on feeding behaviour, glucose and energy metabolism, circulating hormones (luteinising hormone, testosterone, insulin and corticosterone) and hypothalamic neuronal activity. Kp increased plasma testosterone levels, had an anorexigenic effect and increased lipid catabolism, as attested by a decreased respiratory exchange ratio (RER). RFRP‐3 also increased plasma testosterone levels but did not modify food intake or energy metabolism. Both RF‐amides increased endogenous glucose production, yet with no change in plasma glucose levels, suggesting that these peptides provoke not only a release of hepatic glucose, but also a change in glucose utilisation. Finally, plasma insulin and corticosterone levels did not change after the RF‐amide treatment. The Kp effects were associated with an increased c‐Fos expression in the median preoptic area and a reduction in pro‐opiomelanocortin immunostaining in the arcuate nucleus. No effects on neuronal activation were found for RFRP‐3. Our results provide further evidence that Kp is not only a very potent hypothalamic activator of reproduction, but also part of the hypothalamic circuit controlling energy metabolism.

A decrease in plasma glucose levels is required for increased endogenous glucose production with a single administration of a sodium-glucose co-transporter-2 inhibitor tofogliflozin.

To investigate whether changes in endogenous glucose production (EGP) and insulin and glucagon levels are elicited by the decrease in plasma glucose (PG) levels induced by the sodium-glucose co-transporter-2 (SGLT2) inhibitor tofogliflozin. We evaluated EGP in 12 Japanese patients with type 2 diabetes under the conditions of no drugs administered (CON), single administration of the SGLT2 inhibitor tofogliflozin (TOF), and single administration of TOF with adjustment of PG levels with exogenous glucose infusion to mimic changes in PG levels observed with CON (TOF + G). We evaluated changes in EGP and levels of C-peptide and glucagon from baseline to 180 minutes after drug administration. Endogenous glucose production decreased in the CON (-0.22 ± 0.11 mg/kg·min) and TOF + G experiments (-0.31 ± 0.24 mg/kg·min), but not in the TOF experiment (+0.08 ± 0.19 mg/kg·min). The decrease in C-peptide was significantly greater in the TOF experiment (-0.11 ± 0.06 nmol/L) than in the CON (-0.03 ± 0.06 nmol/L) and the TOF + G experiments (-0.01 ± 0.11 nmol/L), while the increase in glucagon was significantly greater in the TOF experiment (+11.1 ± 6.3 pmol/L), but not in the TOF + G experiment (+8.6 ± 7.6 pmol/L) compared to the CON experiment (+5.1 ± 4.3 pmol/L). These results indicate that the decrease in PG levels induced by SGLT2 inhibitor administration is required for the increase in EGP and decrease in insulin secretion.

���������Ҳ ���ղ̲���� �������� � ���² ��� ��������������Ͳ� ��Բ��̲ ������

Experimental studies are among the important and promising approaches in the studying of the pathogenesis of pulmonary emphysema (PE). They make it possible to trace and understand the sequence of metabolic disorders wich occur in this condition. The aim of the trial was to study the nature of biochemical changes in blood plasma during the course of experimental PE. Materials and methods. The study was carried out on 36 sexually mature, outbred, white rats of both sexes, weighing 180-200 g, which were kept on a standard vivarium diet. Experimental papain PE in white rats was induced by a single intratracheal administration of 0.5 ml of papain solution (Merck KGaA, Germany) at a dose of 100 mg / kg body weight under light ether anesthesia. The rats were withdrawn from the experiment by decapitation under light ether anesthesia 10, 20, 30, 50 and 60 days after the onset of the disease. Biochemical studies of blood plasma - the content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), protein, urea, creatinine, total bilirubin, glucose were carried out using automatic biochemical analyzer Selectra Pro-M (Netherlands). Results. It was found that 10 days after the onset of the disease, the levels of ALT and AST significantly decreased by 37%. The trend towards a decrease in ALT persisted after 20, 30 and 60 days; AST � after 20, 30, 50 and 60 days. It was found that the blood plasma protein significantly decreased 10 and 20 days after the onset of the disease by 33% and 38%, respectively. At the same time, the urea also decreased after 10 days by 36% and by 32% after 20 days. A similar trend of changes was found when studying the level of creatinine in blood plasma. After 10 and 20 days, creatinine decreased by 36% and 37%, respectively. As for total bilirubin, its blood plasma contentration increased by 68% after 10 days, and by 38% after 20 days. There were no changes in plasma glucose levels 10, 20, 30, 50 and 60 days after the onset of the disease. Conclusions. Experimental PE is characterized by the most pronounced changes in blood plasma biochemical parameters 10 and 20 days after the onset of the disease, which is manifested by a decrease of aminotransferases � ALT and AST, a decrease in total protein, urea, creatinine, and an increase of total bilirubin. Key words: experimental pulmonary emphysema, alanine aminotransferase, aspartate aminotransferase, protein, urea, creatinine, bilirubin, glucose. U

A "Western Diet" promotes symptoms of hepatic steatosis in spontaneously hypertensive rats.

Systemic hypertension, characterized by elevated blood pressure ≥140/90mmHg, is a major modifiable risk factor for cardiovascular disease. Hypertension also associates with non-alcoholic fatty liver disease (NAFLD), which is becoming common due to a modern diet and lifestyle. The aim of the present study was to examine whether a high-fat "Western" diet had effects on hypertension and associated NAFLD. Normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were placed on a normal chow or high-fat diet for 8weeks; blood pressure was measured fortnightly and body weight recorded weekly. As expected, SHR had elevated blood pressure compared to WKY. Diet did not influence blood pressure. Compared to SHR, WKY rats gained more weight, associating with increased white adipose tissue weight. Normotensive rats also had higher plasma cholesterol and triglycerides in response to a "Western" diet, with no changes in plasma glucose levels. Neither strain developed atherosclerosis. Interestingly, high-fat diet-fed SHR had increased liver weight, associating with a significant level of hepatic lipid accumulation not observed in WKY. Further, they exhibited hepatocellular ballooning and increased hepatic inflammation, indicative of steatohepatitis. These findings suggest that a high-fat "Western" diet promotes features of NAFLD in SHR, but not WKY rats. Importantly, the high-fat diet had no effect on blood pressure.

Dietary starch promotes hepatic lipogenesis in barramundi (Lates calcarifer).

Barramundi (Lates calcarifer) are a highly valued aquaculture species, and, as obligate carnivores, they have a demonstrated preference for dietary protein over lipid or starch to fuel energetic growth demands. In order to investigate how carnivorous fish regulate nutritional cues, we examined the metabolic effects of feeding two isoenergetic diets that contained different proportions of digestible protein or starch energy. Fish fed a high proportion of dietary starch energy had a higher proportion of liver SFA, but showed no change in plasma glucose levels, and few changes in the expression of genes regulating key hepatic metabolic pathways. Decreased activation of the mammalian target of rapamycin growth signalling cascade was consistent with decreased growth performance values. The fractional synthetic rate (lipogenesis), measured by TAG 2H-enrichment using 2H NMR, was significantly higher in barramundi fed with the starch diet compared with the protein diet (0·6 (se 0·1) v. 0·4 (se 0·1) % per d, respectively). Hepatic TAG-bound glycerol synthetic rates were much higher than other closely related fish such as sea bass, but were not significantly different (starch, 2·8 (se 0·3) v. protein, 3·4 (se 0·3) % per d), highlighting the role of glycerol as a metabolic intermediary and high TAG-FA cycling in barramundi. Overall, dietary starch significantly increased hepatic TAG through increased lipogenesis. Compared with other fish, barramundi possess a unique mechanism to metabolise dietary carbohydrates and this knowledge may define ways to improve performance of advanced formulated feeds.

Correlation between 12\u03b1-hydroxylated bile acids and insulin secretion during glucose tolerance tests in rats fed a high-fat and high-sucrose diet

BackgroundPreviously, we found a significant relationship in a rat study between energy intake and bile acid (BA) metabolism especially 12α-hydroxylated (12αOH) BAs. The present study was designed to reveal relationships among BA metabolism, glucose tolerance, and cecal organic acids in rats fed a high-fat and high-sucrose diet (HFS) by using multivariate and multiple regression analyses in two types of glucose tolerance tests (GTTs).MethodsMale WKAH/HkmSlc rats were fed with a control or a HFS for 13 weeks. Oral glucose tolerance test (OGTT) and intraperitoneal glucose tolerance test (IPGTT) were performed at week 9 and 11, respectively. BAs were analyzed by using ultra high-performance liquid chromatography-mass spectrometry. Organic acid concentrations in cecal contents were analyzed by using ultra high-performance liquid chromatography with post-column pH buffered electric conductivity method.ResultsA positive correlation of aortic 12αOH BA concentration was observed with energy intake and visceral adipose tissue weight. We found that an increase of 12αOH BAs in enterohepatic circulation, intestinal contents and feces in the HFS-fed rats compared to those in control rats regardless of no significant increase of total BA concentration in the feces in the test period. Fecal 12αOH BA concentration was positively correlated with maximal insulin level in OGTT and area under curve of insulin in IPGTT. There was a positive correlation between aortic 12αOH BAs concentration and changes in plasma glucose level in both OGTT and IPGTT. In contrast, a decrease in the concentration of organic acids was observed in the cecal contents of the HFS-fed rats. Multiple linear regression analysis in the IPGTT revealed that the concentrations of aortic 12αOH BA and cecal acetic acid were the predictors of insulin secretion. Moreover, there was a positive correlation between concentration of portal 12αOH BAs and change in insulin concentration of peripheral blood in the IPGTT.ConclusionThe distribution analysis of BA compositions accompanied by GTTs revealed a close relationship between 12αOH BA metabolism and insulin secretion in GTTs in rats.

Labile Hemoglobin - A Biochemical Entity

Diabetes mellitus is a major health disease and may vary in clinical presentation and progression. Although Glucose Fasting and Post prandial levels give a measure of the current plasma glucose level, Glycated haemoglobin is the key analyte used to assess the glycemic control and risk of complications of patients with diabetes. Labile hemoglobin A1c is also known as pre-HbA1c or LA1c or pre-glycohemoglobin. It is an unstable form, (a Schiff base) formed during non-enzymatic glycation of hemoglobin. The concentration of labile fraction varies with acute change in plasma glucose level. Labile hemoglobin may potentially interfere in the estimation of HbA1c and cause a falsely low value and may even hamper or delay the prompt treatment required in diabetics. This calls for a detailed and careful study of chromatograms generated for each sample.

VEGF-A and blood vessels: a beta cell perspective.

Reciprocal signalling between the endothelium and the pancreatic epithelium is crucial for coordinated differentiation of the embryonic endocrine and exocrine pancreas. In the adult pancreas, islets depend on their dense capillary network to adequately respond to changes in plasma glucose levels. Vascular changes contribute to the onset and progression of both type 1 and type 2 diabetes. Impaired revascularisation of islets transplanted in individuals with type 1 diabetes is linked to islet graft failure and graft loss. This review summarises our understanding of the role of vascular endothelial growth factor-A (VEGF-A) and endothelial cells in beta cell development, physiology and disease. In addition, the therapeutic potential of modulating VEGF-A levels in beta and beta-like cells for transplantation is discussed.

Protective Effects of Calcitriol Against Fructose‐induced Hyperglycaemia and Dyslipidaemia in Male Albino Wistar Rats

Hyperglycemia and lipidaemia have been found to produce adverse metabolic alterations in glucose and lipid metabolism. The study investigates the preventive role of calcitriol supplementation on fructose‐induced hyperglycaemia and dyslipidaemia in fructose‐drinking Albino Wistar rats. Twenty five male Albino rats were used. The rats were divided into 5 groups of 5 animals each. Group I: Control; received normal rat feed + distilled water, Group II: Received normal rat feed + 125 μg/kg of Calcitriol (CTR), Group III: Received normal rat feed + 10% fructose solution (FDR), Group IV: Received normal rat feed + 10% fructose solution (FDR) + 0.3 mg/kg of glibenclamide (GLIB). Group V: Received normal rat feed + 10% fructose solution (FDR) + 125 μg/kg of Calcitriol (CTR). For the induction of hyperglycaemia and lipidaemia rats were given 10% fructose solution as drinking water for eight weeks. The levels of fasting sugar and HbA1c were measured. Changes in body weights and lipid profile of rats were determined. CTR group exhibited no significant change in plasma glucose levels, HbA1c and body weights when compared to the control. In FDR group fasting sugar levels, glycated haemoglobin (HbA1c) and weights were found to be significantly increased compared group I. Glibenclamide administration in GLIB + FDR group effectively abolished the fructose‐induced hyperglycaemia and glycated haemoglobin in rats when compared to FDR group. In FDR + CTR group calcitriol supplementation successfully blocked and prevented the fructose‐induced increased in fasting sugar, HbA1c levels and weight in rats when compared with FDR group. CTR group exhibited no significant changes in lipid profile parameters compared control. FDR exhibited a significant increase in serum total cholesterol, when compared to control group. Similarly, fructose feeding resulted in a significant elevation in triglycerides levels in comparison to the control rats. FDR group rats had elevated levels of LDL‐C which was significant when compared with the control group. Although, high density lipoprotein cholesterol was increased in FDR group, the increased was not significant and the result was comparable to that of the control. In FDR + CTR group, oral calcitriol supplementation potentially prevented fructose in inducing alterations in serum lipid profiles when compared to FDR group. The result showed that calcitriol supplemention infructose‐drinking rats protects against hyperglycaemia and dyslipidaemia.Support or Funding InformationFunding is through the Tertiary Education Trust Fund, Nigeria. When an acceptance and invitation letter is forwarded to the Fund atleast 3 months before the conference timeThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract WP339: Modulation of Gut Microbiota Improves Outcomes After Ischemic Stroke by Reducing Lipopolysaccharide-Induced Inflammation in the Ischemic Brain of Diabetic Mice

Background and Aims: Gut dysbiosis, an imbalance of gut microbiota, is associated with host inflammation due to the translocation of Gram-negative bacteria-derived lipopolysaccharide (LPS), resulting from increased gut permeability. Inflammation plays a key role in the pathophysiology of ischemic stroke. Here, we investigated the effect of gut dysbiosis on acute ischemic brain injury. Methods: Fecal bacteria were analyzed via 16S and 23S rRNA-targeted quantitative reverse transcription-polymerase chain reaction and the outcome of focal cerebral ischemia was examined in lean littermates (db/+), type 2 diabetic mice (db/db), and db/db mice with oral administration of the non-absorbable antibiotic polymyxin B (db/db+PL-B) (n=5-9/group). Results: Mice from the db/db+PL-B group had selectively attenuated fecal bacterial count of the Gram-negative bacteria Enterobacteriaceae (p&lt;0.01), and reduced plasma LPS levels (p&lt;0.05) and gut permeability (p&lt;0.05) without a change in plasma glucose levels compared to those in db/db mice. Polymyxin B was not detected in the blood of db/db+PL-B mice. In addition, antibiotic pre-treatment significantly reduced infarct size (p&lt;0.05), blood-brain barrier leakage (p&lt;0.05), inflammatory reactions in the brain, such as IL-6 (p&lt;0.01), IL-1β (p&lt;0.01), and TNF-α (p&lt;0.05), improved neurological function (p&lt;0.05), and survival rates (p&lt;0.05) following cerebral ischemia. Furthermore, db/db + PL-B mice had significantly reduced LPS (p&lt;0.05) and expression of TLR4 (p&lt;0.01), the LPS receptor, and inflammatory cytokine levels, such as IL-6 (p&lt;0.01), IL-1β(p&lt;0.01), and TNF-α (p&lt;0.05), in the ischemic hemisphere. Conclusions: These findings suggest that LPS-induced inflammation may be a mechanism that links gut dysbiosis to ischemic cerebral injury, and that modulation of gut microbiota may be a potential therapeutic strategy to improve the stroke outcome.

Glycemic Variability and Brain Glucose Levels in Type 1 Diabetes.

The impact of glycemic variability on brain glucose transport kinetics among individuals with type 1 diabetes mellitus (T1DM) remains unclear. Fourteen individuals with T1DM (age 35 ± 4 years; BMI 26.0 ± 1.4 kg/m2; HbA1c 7.6 ± 0.3) and nine healthy control participants (age 32 ± 4; BMI 23.1 ± 0.8; HbA1c 5.0 ± 0.1) wore a continuous glucose monitor (Dexcom) to measure hypoglycemia, hyperglycemia, and glycemic variability for 5 days followed by 1H MRS scanning in the occipital lobe to measure the change in intracerebral glucose levels during a 2-h glucose clamp (target glucose concentration 220 mg/dL). Hyperglycemic clamps were also performed in a rat model of T1DM to assess regional differences in brain glucose transport and metabolism. Despite a similar change in plasma glucose levels during the hyperglycemic clamp, individuals with T1DM had significantly smaller increments in intracerebral glucose levels (P = 0.0002). Moreover, among individuals with T1DM, the change in brain glucose correlated positively with the lability index (r = 0.67, P = 0.006). Consistent with findings in humans, streptozotocin-treated rats had lower brain glucose levels in the cortex, hippocampus, and striatum compared with control rats. These findings that glycemic variability is associated with brain glucose levels highlight the need for future studies to investigate the impact of glycemic variability on brain glucose kinetics.

Physiological responses of anti-predation in prey fish to the threat of piscivorous fish in different underwater visibility conditions

ABSTRACT Considering that the anti-predation behaviour of prey fishes may vary with predator hunting strategy, we experimentally investigated the physiological responses of Astyanax bimaculatus (Linnaeus, 1758) shoals to the presence of two piscivorous fish species with different hunting modes: sit-and-wait and active pursuit. In addition, we evaluated the influence of underwater visibility conditions on the interaction between predator and prey. We tested the hypotheses that: (i) prey plasma cortisol and glucose levels vary according to piscivore hunting strategy, and (ii) no reduction in plasma glucose and cortisol levels takes place in turbid environments due to the inability of prey to accurately recognise predators by non-visual signals. The results revealed that the presence of piscivorous fish increased plasma cortisol levels in prey, with no significant difference recorded between the two hunting strategy treatments. We also observed no significant change in plasma glucose levels in different water transparency conditions. Thus, we conclude that physiological changes in the selected prey fish do not vary with predator hunting mode, and it is therefore necessary to consider the ability of the prey to recognise and evaluate danger, regardless of piscivore hunting strategy.

Change in Glucose Levels during Pregnancy and Parturition in Normoglycemic Women Indicated by Flash Glucose Monitoring System

Accurate knowledge of changes in plasma glucose levels during pregnancy and parturition in normoglycemic women is important for safe management of hyperglycemic disorders in pregnancy. However, there are few reports showing long-term changes in glucose levels over the entire pregnancy period. Flash glucose monitoring (FGM) is a new sensor technology that enables us to ascertain these glucose levels. This is the first study in Japan to monitor glucose levels during this period in normoglycemic, pregnant women by using FGM, which was performed once in non-pregnant women and up to 5 times (first trimester, second trimester, third trimester, parturition, and 3-month postpartum) in pregnant women. Twenty-one non-pregnant women and 9 pregnant women participated in the study. In non-pregnant women, the average age and BMI were 34.4±9.1 years and 20.4±1.5 kg/m2, respectively; the average glucose level was 101.9±20.8 mg/dL, with no difference in age groups. In pregnant women, the average age and BMI were 33.0±2.7 years and 19.0±1.4 kg/m2, respectively. The average glucose levels were 99.8±5.0 mg/dL at first trimester, 85.1±13.0 mg/dL at second trimester, 92.0±7.6 mg/dL at third trimester, 107.3±8.1 mg/dL during parturition, and 95.7±10.0 mg/dL at 3-month postpartum. Compared to glucose levels of non-pregnant women, those of pregnant women were significantly lower at second and third trimester, and returned to the same level at 3-month postpartum. The glucose level during parturition was significantly highest; the proportion of time to achieve optimal target glucose level of 80-110 mg/dL was 62.3±19.9% and the highest value was 244 mg/dL. Maternal and neonatal clinical courses were uneventful in all pregnant cases. It is thus necessary to evaluate to what extent peak value and duration of hyperglycemia affects birth outcome. Disclosure A. Nishimura: None. M. Furuta: None. Y. Chigusa: None. M. Maeno: None. M. Fukami: None. S. Harashima: Advisory Panel; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Sanofi K.K.. Research Support; Self; Sanofi K.K.. Speaker's Bureau; Self; Tanabe Mitsubishi KK. Advisory Panel; Self; Tanabe Mitsubishi KK. Speaker's Bureau; Self; Novartis Pharma K.K., Eli Lilly and Company, Ono Pharmaceutical Co., Ltd..