Decline In Glucose Research Articles

Traditional Chinese Patent Medicine for Treating Impaired Glucose Tolerance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

To assess the effectiveness and safety of Traditional Chinese patent medicines (TCPMs) for managing impaired glucose tolerance (IGT). Seven databases were searched to identify eligible trials published from incepting to May 1, 2016. Randomized controlled trials (RCTs) involving TCPM for IGT with a minimum follow-up duration of 6 months were included for analysis. Data extraction and quality assessment were performed by two reviewers independently. Data synthesis was analyzed using Review Manager 5.3 software. Subgroup analysis was carried out to assess the robustness of results of meta-analysis. Eighteen trials with a total of 3172 participants met the inclusion criteria. The methodological quality of the RCTs was variable. Comparing with receiving lifestyle modification (LM) alone, TCPM plus LM was significantly better at reducing the incidence of diabetes (risk ratio [RR] 0.45; 95% confidence interval [CI] 0.36-0.57, p < 0.00001) and normalizing the blood glucose (RR 0.72; 95% CI 0.64-0.82, p < 0.00001). TCPM plus LM was superior in decreasing the levels of 2hPG, body mass index (BMI), fasting insulin, and 2 h insulin compared with LM alone (2hPG: mean difference [MD] -1.13; 95% CI -1.68 to -0.58, p < 0.0001; BMI: MD -0.42; 95% CI -0.71 to -0.14, p = 0.004; fasting insulin: MD -2.44; 95% CI -3.79 to -1.09, p = 0.0004; and 2 h insulin: MD -8.26; 95% CI -8.47 to -8.05, p < 0.00001). Compared with placebo plus LM, TCPM plus LM was superior in reducing diabetes (RR 0.54; 95% CI 0.42-0.69, p < 0.00001) and normalizing blood glucose (RR 0.55; 95% CI 0.41-0.73, p < 0.00001; the interventions were also associated with a decline in the two-hour postprandial blood glucose (2hPG) levels (MD -1.45; 95% CI -2.11 to -0.79, p < 0.0001) and BMI levels (MD -1.12; 95% CI -2.00 to -0.24, p < 0.0001). There were no significant differences in adverse events between two groups. Subgroup analysis found no significant difference in overall effects among all study characteristics, indicating that the overall effects were stable. The study indicated that TCPM combined with moderate lifestyle modification had significant effect on IGT. Further studies are needed to provide more reliable evidence. The PROSPERO registration is No. CRD42016039312.

Exploring the potential of black tea based flavonoids against hyperlipidemia related disorders

BackgroundIn recent decade, Hyperlipidemia related disorders like obesity, hypercholesterolemia and diabetes are considered as the leading killers for mankind. Fundamental nexus between nutrition and health diverting the consumers focus towards plant based natural products as a remedy against various metabolic syndrome. Considering this, present study was conducted to explicate the role of black tea polyphenols such as Theaflavins and thearubigins therapeutic potential to tackle targeted maladies especially oxidative stress related disorders like hypercholesterolemia and diabetes.MethodsThe mandate of current investigation was to explore the hypoglycemic and hypocholestrolemic perspective of isolated theaflavin and thearubigins through a model feeding trial. For the purpose, theaflavin & thearubigins were isolated from black tea through solvent partition method and utilize to form three types of nutraceutical drinks (theaflavin, thearubigins & theaflavin + thearubigins based) alongside control to be further utilized in bioefficacy trial. In bioefficacy trial, three types of independent studies were design on the bases of diet by involving 20 male wistar rats in each study (5 for each group). In study I, normal diet was administrated while, in study II & III high cholesterol and high sucrose diet was given, respectively along with prepared nutraceutical drinks to synchronize their therapeutic effect for a period of 56 days. At the termination of trial, Feed & drink intakes, body weight, total cholesterol, LDL, HDL, triglycerides, glucose and insulin levels were measured.ResultsThe results indicated reduction in cholesterol, LDL and triglycerides levels of experimental rats in all studies with significant increase in HDL. In this context, theaflavin based drink imparted maximum reduction in cholesterol (3.75, 11.03 & 10.39%), LDL (3.84, 14.25& 10.84%) & triglycerides (2.99, 8.54 & 6.65%) in respective studies compared to thearubigins and theaflavin + thearubigins based drinks. However, theaflavin+ thearubigins based drink caused highest glucose decline and maximum insulin increase in all studies as compared to other nutraceutical drinks. The reported value for the insulin increase were 13.02 ± 1.02 & 14.55 ± 1.13, 10.09 ± 0.15 & 11.59 ± 0.86 for Hyperglycemic and Hypocholestrolemic rats respectively compared to control (7.84 ± 0.45 & 9.10 ± 0.41) for study I and II.ConclusionsIn the nutshell, theaflavin and thearubigins based dietary interventions are helpful to alleviate the hypercholestrolemia and hyperglycemia and should be promoted as parallel therapy to combat these disorders.

Implications of pancreatic cancer with diabetes mellitus on patient outcomes and care: A matched case-control study.

239 Background: The aim of this case-control study was to determine the impact of DM on survival in pancreatic cancer patients, and to examine the impact of pancreatic cancer on glycemic control in DM. Methods: Ninety-two patients with newly diagnosed pancreatic cancer from 2007 to 2015 with DM were identified from the institutional Cancer Registry and matched to ninety-two pancreatic cancer patients without DM according to age, gender, and year of pancreatic cancer diagnosis. The file was linked to the electronic medical record to obtain information on DM and pancreatic cancer therapies, and laboratory results. Overall survival (OS) was estimated with the Kaplan-Meier method and compared by Cox regression analysis. Mixed models were used to compare hemoglobin A1c (HbA1c) and glucose over time. Results: Mean age of the entire pancreatic cancer cohort was 70 years, most (92%) were white, most common (88%) histology was adenocarcinoma, and majority (41%) were stage IV. No differences in age, race/ethnicity, histology, or tumor stage were detected between patients with and without DM, although DM patients had higher body mass index (P = 0.014). Mean ca 19-9 (U/ml) was 804 for diabetics, and 395 for non-diabetics. Among those with DM the mean HbA1c during the year following cancer diagnosis was 7.3%. Time (days since diagnosis) was significant in DM patients (p = 0.014) as HbA1c decreased over time. Mean glucose during the year following diagnosis among DM patients was significantly higher compared to non-DM patients [160.6 (SD = 38.0) versus 117.2 (SD = 19.0); p &lt; 0.001]. Both groups had a decline in glucose over time (p = 0.008). In Kaplan-Meier survival analysis (median follow-up time of 11.9 months), 2 year overall survival was estimated at 15% [95% CI: 8-24%] for DM patients versus 26% [95% CI: 17-36%] in non-DM patients. Hazard ratio (for matched pairs) was 1.15 (95% CI: 0.75-1.77; p = 0.51). Conclusions: DM did not adversely impact survival in patients with pancreatic cancer. Pancreatic cancer did not affect glycemic control. Elevated ca 19-9 in diabetic patients may be an unreliable marker for gauging disease progression.

Timing of Exercise Affects Glycemic Control in Type 2 Diabetes Patients Treated with Metformin.

Objective The purpose of the study was to examine the acute effects of the timing of exercise on the glycemic control during and after exercise in T2D. Methods This study included 26 T2D patients (14 women and 12 men) who were treated with metformin. All patients were tested on four occasions: metformin administration alone (Metf), high-intensity interval training (HIIT) performed at 30 minutes (EX30), 60 minutes (EX60), and 90 minutes (EX90) postbreakfast, respectively. Glucose, insulin, and superoxide dismutase (SOD) activity were examined. Results Glucose decreased significantly after the exercise in EX30, EX60, and EX90. Compared with Metf, the decline in glucose immediately after the exercise was larger in EX30 (−2.58 mmol/L; 95% CI, −3.36 to −1.79 mmol/L; p < 0.001), EX60 (−2.13 mmol/L; 95% CI, −2.91 to −1.34 mmol/L; p < 0.001), and EX90 (−1.87 mmol/L; 95% CI, −2.65 to −1.08 mmol/L; p < 0.001), respectively. Compared with Metf, the decrease in insulin was larger in EX30 and EX60 (both p < 0.001). Conclusions Timing of exercise is a factor to consider when prescribing exercise for T2D patients treated with metformin. This trial is registered with ChiCTR-IOR-16008469 on 13 May 2016.

Colon Ascendens Stent Peritonitis (CASP) Induces Excessive Inflammation and Systemic Metabolic Dysfunction in a Septic Rat Model.

The colon ascendens stent peritonitis (CASP) surgery induces a leakage of gut contents, causing polymicrobial sepsis related to post-operative multiple organ failure and death in surgical patient. To evaluate the effects of CASP on multiple organs, we analyzed the systemic metabolic consequences in liver, kidney, lung, and heart of rats after CASP by employing a combination of metabolomics, clinical chemistry, and biological assays. We found that CASP surgery after 18 h resulted in striking elevations of lipid, amino acids, acetate, choline, PC, and GPC in rat liver together with significant depletion of glucose and glycogen. Marked elevations of organic acids including lactate, acetate, and creatine and amino acids accompanied by decline of glucose, betaine, TMAO, choline metabolites (PC and GPC) nucleotides, and a range of organic osmolytes such as myo-inositol are observed in the kidney of 18 h post-operative rat. Furthermore, 18 h post-operative rats exhibited accumulations of lipid, amino acids, and depletions of taurine, myo-inositol, choline, PC, and GPC and some nucleotides including uridine, inosine, and adenosine in the lung. In addition, significant elevations of some amino acids, uracil, betaine, and choline metabolites, together with depletion of inosine-5'-monophosphate, were only observed in the heart of 18 h post-operative rats. These results provide new insights into pathological consequences of CASP surgery, which are important for timely prognosis of sepsis.

Antihyperglycemic effect of hesperetin, a citrus flavonoid, extenuates hyperglycemia and exploring the potential role in antioxidant and antihyperlipidemic in streptozotocin-induced diabetic rats

Diabetes is the major health problem in modern civilization which occurs due to inadequate metabolism of carbohydrate and lipid could cause tremendous changes in the metabolic activities of liver. In this study, we investigated the antihyperglycemic, antioxidant and antihyperlipidemic effects of hesperetin, a citrus flavonoid against streptozotocin (STZ)-induced experimental rats. To stimulate diabetes mellitus, rats were injected with STZ intraperitoneally at a single dose of 45mg/kg. STZ induced rats showed marked increase in the level of plasma glucose and significant reduction in the level of plasma insulin. The activities of carbohydrate metabolic enzymes, hepatic glycogen, lipid profiles, enzymic antioxidants in circulatory system and pancreas, hepatic and renal functional markers were explored. Supplementation with hesperetin (40mg/kg b.w) to STZ-induced experimental rats for 45days established a significant decline in plasma glucose and a marked improvement in plasma insulin and glycogen levels in STZ-induced rats. The altered activities of hepatic glucose metabolic enzymes, lipid profiles, enzymic antioxidants and serum biomarkers of liver and kidney toxicity were restored to almost normal. The acquired outcome were compared with glibenclamide (1mg/kg b.w), a standard oral hypoglycemic drug. Hesperetin treatment was found to be efficient in protecting the normal histological manifestation of hepatic, renal and insulin positive β-cells in STZ induced rats. On the basis of current experimental findings, we concluded that administration of hesperetin attenuates the hyperglycemia and dyslipidemia through ameliorating antioxidant competence in STZ-induced experimental rats.

Improvement of glycemic state among responders to Sofosbuvir-based treatment regimens: Single center experience.

Chronic HCV infection has emerged as a complex multifaceted disease with manifestations extending beyond the liver. HCV plays a direct role in glucose metabolism leading to both insulin resistance and type 2 diabetes. To evaluate the changes in the glycemic state following Sofosbuvir-based treatment regimens in diabetic HCV patients. Four hundred chronic hepatitis C patients who underwent Sofosbuvir-based treatment regimens were retrospectively screened. Sixty-five diabetic HCV patients only enrolled in our analysis. Baseline demographic and laboratory data were recorded. Pretreatment Transient elastography was performed. At 24-week post EOT (SVR24), Fasting Plasma glucose, and Hemoglobin A1c were re-evaluated and compared with baseline. All enrolled diabetic patients were responders. They showed statistically significant decline in Fasting Plasma glucose and Hemoglobin A1c values at SVR24. Whatever the degree of hepatic fibrosis, the level of Fasting Plasma glucose and Hemoglobin A1c decreased at SVR24 in comparison to baseline level. Fifty-one patients showed improvement in their Hemoglobin A1c values at SVR24 and this improvement was more likely to occur among patients with low Body mass index. The reduction in Fasting Plasma glucose >20 mg/dL (>1.1 mmol/L) and Hemoglobin A1c ≥0.5% was not associated with age, gender or hepatic fibrosis stage. Sofosbuvir-based regimens are a highly efficient antiviral therapy for diabetic chronic HCV patients resulted in improvement in Fasting Plasma glucose and Hemoglobin A1c.

Atypical blood glucose response to continuous and interval exercise in a person with type 1 diabetes: a case report

BackgroundTherapy must be adapted for people with type 1 diabetes to avoid exercise-induced hypoglycemia caused by increased exercise-related glucose uptake into muscles. Therefore, to avoid hypoglycemia, the preexercise short-acting insulin dose must be reduced for safety reasons. We report a case of a man with long-lasting type 1 diabetes in whom no blood glucose decrease during different types of exercise with varying exercise intensities and modes was found, despite physiological hormone responses.Case presentationA Caucasian man diagnosed with type 1 diabetes for 24 years performed three different continuous high-intensity interval cycle ergometer exercises as part of a clinical trial (ClinicalTrials.gov identifier NCT02075567). Intensities for both modes of exercises were set at 5% below and 5% above the first lactate turn point and 5% below the second lactate turn point. Short-acting insulin doses were reduced by 25%, 50%, and 75%, respectively. Measurements taken included blood glucose, blood lactate, gas exchange, heart rate, adrenaline, noradrenaline, cortisol, glucagon, and insulin-like growth factor-1. Unexpectedly, no significant blood glucose decreases were observed during all exercise sessions (start versus end, 12.97 ± 2.12 versus 12.61 ± 2.66 mmol L−1, p = 0.259). All hormones showed the expected response, dependent on the different intensities and modes of exercises.ConclusionsPeople with type 1 diabetes typically experience a decrease in blood glucose levels, particularly during low- and moderate-intensity exercises. In our patient, we clearly found no decline in blood glucose, despite a normal hormone response and no history of any insulin insensitivity. This report indicates that there might be patients for whom the recommended preexercise therapy adaptation to avoid exercise-induced hypoglycemia needs to be questioned because this could increase the risk of severe hyperglycemia and ketosis.

Antihyperglycaemic activity of the methanol extract from leaves of Eremophila maculata (Scrophulariaceae) in streptozotocin-induced diabetic rats

This study was designed to evaluate the antihyperglycaemic activity of the methanol leaf extract of Eremophila maculata (EMM) both in vitro and in vivo. The antihyperglycaemic activity was assessed in vitro using differentiated 3T3-L1 adipocytes, whereas in-vivo effect was evaluated in streptozotocin-induced diabetic rats. Chemical profiling of EMM was done using LC-ESI-MS techniques. Molecular modelling experiments of the identified compounds were performed using C-Docker protocol. Eremophila maculata slightly enhanced cellular glucose uptake and utilization in vitro by 3.92% relative to the untreated control. A stronger in-vivo effect was observed for EMM and its dichloromethane fraction. A pronounced elevation in serum insulin by 88.89 and 66.67%, respectively, accompanied by an apparent decline in fasting blood glucose (FBG) level by 65.60 and 70.37% comparable to streptozotocin-induced diabetic rats was observed. This effect was stronger than that of the reference drug glibenclamide (GLB). Chemical profiling of EMM revealed that leucoseptoside A, verbascoside, syringaresinol-4-O-β-D-glucopyranoside, pinoresinol-4-O-β-D-glucopyranoside and pinoresinol-4-O-[6″-O-(E)-feruloyl]-β-D-glucopyranoside are the major compounds. Molecular modelling showed that martynoside, verbascoside and phillygenin exhibited the highest inhibition to human pancreatic α-amylase (HPA), maltase glucoamylase (MGAM) and aldose reductase (AR), respectively. Eremophila maculata offers an interesting relatively safer antihyperglycaemic candidate comparable to synthetic analogues.

CL 316, 243 mediated reductions in blood glucose are enhanced in RIP140−/− mice independent of alterations in lipolysis

The β-3 adrenergic agonist CL 316, 243 acutely lowers blood glucose through a mechanism thought to involve fatty-acid induced insulin release. The purpose of this study was to determine if ablation of the nuclear receptor, receptor-inactivating protein 140 (RIP140), altered this response. Here, we used a single injection of CL 316, 243 (1 mg/kg) and found that whole body RIP140−/− mice had a greater decline in blood glucose over 2 h. This occurred alongside increased hexokinase II (HKII) protein content in adipose tissue and skeletal muscle, but independent of changes in circulating insulin or indices of lipolysis. These data indicate that RIP140 has a unique role in the acute effect of β-3 adrenergic receptor activation using CL 316, 243.

A Randomized controlled trial of the effect of yoga and peer support on glycaemic outcomes in women with type 2 diabetes mellitus: a feasibility study

BackgroundType two diabetes is a complex and demanding chronic disease and its impact in a state (Kerala) which leads India in terms of the number of people with Diabetes is profound. Though the male to female ratio among the people with diabetes is roughly equal, women are uniquely and more severely affected. Management of type two Diabetes requires considerable dexterity on the part of the patient to manage drugs, diet and exercise. Therefore, in a low middle-income country like India it is necessary to look at low cost interventions that can empower the patient and build on available resources to help manage diabetes. Hence, we studied the feasibility and effect of two low cost interventions; yoga and peer support on glycaemic and other outcomes among women with type two diabetes.MethodsAn open label parallel three armed randomized control trial was conducted among 124 recruited women with Diabetes for three months. Block randomization with a block length of six was carried out with each group having at least 41 women. In the Yoga arm, sessions by an instructor, consisting of a group of postures coordinated with breathing were conducted for an hour, two days a week. In the peer support arm each peer mentor after training visited 13–14 women with diabetes every week followed by a phone call. The meeting was about applying disease management or prevention plans in daily life.ResultsThere was a trend in decline of fasting plasma glucose in the peer and yoga group and of glycosylated haemoglobin (HbA1c) in the yoga group only, though not significant. A significant decrease was observed in diastolic blood pressure and hip circumference in the yoga group. The process indicated that most (80%) of the women in the yoga group attended classes regularly and 90% of the women in the peer group reported that peer mentoring was useful.ConclusionThe effect of yoga and peer support on glycaemic outcomes was incremental. Longer term studies are necessary to ascertain the benefits shown by this feasibility study.Trial registrationCTRI/2011/12/002227 dated 14/12/2011.

Knocking down amygdalar PTP1B in diet-induced obese rats improves insulin signaling/action, decreases adiposity and may alter anxiety behavior

ObjectiveProtein tyrosine phosphatase 1B (PTP1B) has been extensively implicated in the regulation of body weight, food intake, and energy expenditure. The role of PTP1B appears to be cell and brain region dependent. ResultsHerein, we demonstrated that chronic high-fat feeding enhanced PTP1B expression in the central nucleus of the amygdala (CeA) of rats compared to rats on chow. Knocking down PTP1B with oligonucleotide antisense (ASO) decreased its expression and was sufficient to improve the anorexigenic effect of insulin through IR/Akt signaling in the CeA. ASO treatment reduces body weight, fat mass, serum leptin levels, and food intake and also increases energy expenditure, without altering ambulatory activity. These changes were explained, at least in part, by the improvement of insulin sensitivity in the CeA, decreasing NPY and enhancing oxytocin expression. There was a slight decline in fasting blood glucose and serum insulin levels possibly due to leanness in rats treated with ASO. Surprisingly, the elevated plus maze test revealed an anxiolytic behavior after reduction of PTP1B in the CeA. ConclusionsThus, the present study highlights the deleterious role that the amygdalar PTP1B has on energy homeostasis in obesity states. The reduction of PTP1B in the CeA may be a strategy for the treatment of obesity, insulin resistance and anxiety disorders.

Drought stress affects bioactive compounds in potatoes (Solanum tuberosum L.) relevant to non-communicable diseases

Background: Potatoes react very sensitive to drought during growth, and appropriate plant stress responses may affect metabolites associated with the health quality of tubers.Objective: The aim of this study is to determine the effects of drought stress (DS) on soluble sugars, starch, crude protein, minerals, free amino acids (AAs) and fatty acids (FAs).Design: The experiment was carried out on three potato genotypes during two years with four replications. The plants were grown in pots, in a glasshouse with optimal water supply and under drought stress conditions. After harvest, the tubers of these two variants were analyzed for bioactive compounds relevant to non-communicable diseases (NCDs). Results: Apart from genotypic differences in most parameters, the results revealed that the DS caused a decline in glucose and fructose (P &lt; 0.05, all) in both years, whereas sucrose was increased, especially in the second year with severe stress (P &lt; 0.01). Starch was significantly reduced by moderate stress in the first year (P &lt; 0.01), but less affected in the second year. Crude proteins and total amounts of free amino acids (AAs) were clearly enhanced by the stress in both years (P &lt; 0.05, all), similarly as the minerals magnesium (Mg), potassium (K) and phosphorus (P) (P &lt; 0.05, all), whereas calcium (Ca) declined (P &lt; 0.05). The portion of α-linolenic acid (ALA) on total lipids was elevated in the stress variants (P &lt; 0.01), while oleic acid (OLA), its precursor decreased significantly (P &lt; 0.05), but only in the first year. In the second year, ALA was in general higher and not further induced by the stress. Also OLA was less affected in that year, similarly as all other FAs in both years. Interestingly, Myo-inositol (MI) and lipid acyl hydrolases (LAH) associated with modulation in cell membrane lipids raised by the drought stress in each year (P &lt; 0.01, all). In the second year, MI and LAH data of the drought stressed tubers correlated significantly (r = 0.90, P &lt; 0.01) indicating their joined action within plant stress responses.Conclusions: The biochemical changes induced by DS are not alarming with regard to NCDs. Decline in glucose, fructose and starch, and increase in crude proteins, free AAs, ALA, MI and minerals like Mg, K and P, on the other side, is profitable for the health benefits of tubers. However, a better quality is associated with a decrease in tuber yield.Keywords: potato, drought stress, bioactive compounds, chronic diseases

Metabolic Dysregulation in Hepacivirus Infection of Common Marmosets (Callithrix jacchus).

Chronic hepatitis C has been associated with metabolic syndrome that includes insulin resistance, hepatic steatosis and obesity. These metabolic aberrations are risk factors for disease severity and treatment outcome in infected patients. Experimental infection of marmosets with GBV-B serves as a tangible, small animal model for human HCV infection, and while virology and pathology are well described, a full investigation of clinical disease and the metabolic milieu is lacking. In this study six marmosets were infected intravenously with GBV-B and changes in hematologic, serum biochemical and plasma metabolic measures were investigated over the duration of infection. Infected animals exhibited signs of lymphocytopenia, but platelet and RBC counts were generally stable or even increased. Although most animals showed a transient decline in blood glucose, infection resulted in several fold increases in plasma insulin, glucagon and glucagon-like peptide 1 (GLP-1). All infected animals experienced transient weight loss within the first 28 days of infection, but also became hypertriglyceridemic and had up to 10-fold increases in adipocytokines such as resistin and plasminogen activator inhibitor 1 (PAI-1). In liver, moderate to severe cytoplasmic changes associated with steatotic changes was observed microscopically at 168 days post infection. Collectively, these results suggest that GBV-B infection is accompanied by hematologic, biochemical and metabolic abnormalities that could lead to obesity, diabetes, thrombosis and atherosclerosis, even after virus has been cleared. Our findings mirror those found in HCV patients, suggesting that metabolic syndrome could be conserved among hepaciviruses, and both mechanistic and interventional studies for treating HCV-induced metabolic complications could be evaluated in this animal model.

Establishment of An Alloxan-induced Diabetes Model in Daphnia Pulex.

Objective To establish a Daphnia model of alloxan-induced diabetes. Methods Daphnia were exposed to three different concentrations of alloxan (3, 5, and 10 mmol/L) for 30 minutes. Blood glucose and survival rate were recorded for 72 hours after alloxan insult. Sequence analysis and phylogenetic inference for glucose transporters (GLUT) were clustered with the maximum-likelihood method. Using reverse transcription and quantitative polymerase chain reaction techniques, we investigated the transcriptional changes of GLUT at 12 hours after alloxan (5 mmol/L) exposure. Results Compared with control, 3 mmol/L, and 5 mmol/L as well as 10 mmol/L alloxan initially induced transient blood glucose decline by 15% for 2 hours and 12 hours respectively. In Daphnia with 5 and 10 mmol/L alloxan, their blood glucose was persistently raised by about 150% since after 24-hour insult. Survival rate of Daphnia exposure to alloxan with concentrations of 3, 5, and 10 mmol/L were 90%, 75%, and 25% respectively. We predicted seven GLUT genes in the Daphnia genome and successfully amplified them using real-time polymerase chain reaction. Two of seven GLUT transcripts were down-regulated in Daphnia with 5 mmol/L alloxan-induced diabetes. Conclusion Alloxan-induced diabetes model was successfully established in the Daphnia pulex, suggesting diabetes-relevant experiments can be conducted using Daphnia.

Critical role for GLP-1 in symptomatic post-bariatric hypoglycaemia.

Post-bariatric hypoglycaemia (PBH) is a rare, but severe, metabolic disorder arising months to years after bariatric surgery. It is characterised by symptomatic postprandial hypoglycaemia, with inappropriately elevated insulin concentrations. The relative contribution of exaggerated incretin hormone signalling to dysregulated insulin secretion and symptomatic hypoglycaemia is a subject of ongoing inquiry. This study was designed to test the hypothesis that PBH and associated symptoms are primarily mediated by glucagon-like peptide-1 (GLP-1). We conducted a double-blinded crossover study wherein eight participants with confirmed PBH were assigned in random order to intravenous infusion of the GLP-1 receptor (GLP-1r) antagonist. Exendin (9-39) (Ex-9), or placebo during an OGTT on two separate days at the Stanford University Clinical and Translational Research Unit. Metabolic, symptomatic and pharmacokinetic variables were evaluated. Results were compared with a cohort of BMI- and glucose-matched non-surgical controls (NSCs). Infusion of Ex-9 decreased the time to peak glucose and rate of glucose decline during OGTT, and raised the postprandial nadir by over 70%, normalising it relative to NSCs and preventing hypoglycaemia in all PBH participants. Insulin AUC and secretion rate decreased by 57% and 71% respectively, and peak postprandial insulin was normalised relative to NSCs. Autonomic and neuroglycopenic symptoms were significantly reduced during Ex-9 infusion. GLP-1r blockade prevented hypoglycaemia in 100% of individuals, normalised beta cell function and reversed neuroglycopenic symptoms, supporting the conclusion that GLP-1 plays a primary role in mediating hyperinsulinaemic hypoglycaemia in PBH. Competitive antagonism at the GLP-1r merits consideration as a therapeutic strategy. ClinicalTrials.gov NCT02550145.

Abstract PR429

Background & Objectives: To establish a Daphnia model of alloxan-induced diabetes contributing to conduct diabetes-relevant experiments in daphnid. Materials & Methods: Daphnid were exposure to 30-min 3 concentrations of alloxan (3 mM, 5 mM and 10 mM). Blood glucose and survival rate were recorded for 72 hrs after alloxan insult. Sequence analysis and phylogenetic inference for glucose transporters (GLUTs) were clustered with the maximum-likelihood method. Using reverse transcription and quantitative PCR techniques, we investigated the transcriptional changes of GLUTs at 12 hrs after alloxan (5 mM) exposure. Results: Compared with control, 3 mM, and 5 mM as well as 10 mM alloxan initially induced transient blood glucose decline by 15% for 2 hrs and 12 hrs respectively. In daphnid with 5 and 10 mM alloxan, their blood glucose was persistently raised about 250% since after 24-hr insult. Survival rate of daphnid with 3 mM, 5mM and 10 mM were 90%, 75% and 25%. We predicted seven GLUTs genes in the Daphnia genome and successfully amplified them using RT-PCR. Two of 7 GLUTs transcripts were downregulated in Daphnia with 5 mM alloxan-induced diabetes. Conclusion: This study provides the first evidence that alloxan can induce diabetes in Daphnia pulex possibly by downregulation of glucose transporters (GLUT1 and GLUT2), a new invertebrate model for diabetes.

Averrhoa bilimbi fruits attenuate hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats

Hyperglycemia-mediated oxidative stress plays a major role in the development of diabetic complications. Averrhoa bilimbi Linn. (Oxalidaceae) is a medicinal plant with fruits reported to possess antidiabetic activity. This study evaluated the beneficial effects of the ethyl acetate fraction of A. bilimbi fruit (ABAEE) on the antioxidant/oxidant status in diabetes mellitus. Diabetic rats were treated orally with the ethyl acetate fraction of A. bilimbi fruits at a dose of 25 mg/kg body weight for 60 days. Serum glucose, glycated hemoglobin, plasma insulin, hepatic toxicity markers, antioxidant enzymes, lipid peroxidation products, and liver histopathology were assayed checked after 60 days of extract treatment. Diabetic rats administered ABAEE showed a significant decline in serum glucose, glycated hemoglobin, and also significantly increases the level of plasma insulin, as well as a notable attenuation in thiobarbituric acid-reactive substances, conjugated dienes, and hydroperoxides. ABAEE also modulated hepatic antioxidant potential by significantly increasing the activities of catalase, glutathione peroxidase, glutathione reductase, superoxide dismutase, and reducing glutathione content. The results associated with ABAEE were more significant than those observed following treatment with the standard drug metformin. Histopathological observations showed that ABAEE effectively rescued hepatocytes from oxidative damage without affecting cellular function and structural integrity. High-performance liquid chromatography analysis of ABAEE indicated the presence of phenolic compound, quercetin, indicating that the antidiabetic effect of the extract might be related to quercetin. These results demonstrated the potential beneficial effect of ABAEE on streptozotocin-induced diabetes in rats.

DECLINE IN GLUCOSE LEVELS PRECEDES DEMENTIA IN ELDERLY AFRICAN AMERICANS WITH DIABETES

DECLINE IN GLUCOSE LEVELS PRECEDES DEMENTIA IN ELDERLY AFRICAN AMERICANS WITH DIABETES

Abstract 606: Impaired Glucose Metabolism in the Triggering Receptor Expressed in Myeloid Cells Like Transcript- 1 Null Mice A Link to Obesity

Fat rich foods have been shown to produce increased body weight and diabetes in various strains of mice. When fed ad libitum with a high fat diet (HFD), apolipoprotein E deficient ( apoe -/- ) mice develop hypercholesterolemia, but are not known to be obese. Our laboratory demonstrated that the triggering receptor expressed in myeloid cells (TREM) like transcript-1 (TLT-1), as a potential target for intervention during atherosclerosis, diabetes, and obesity. Crossing the treml1 -/- mouse onto an apoe -/- background (DKO), we found DKO mice had smaller lesions than apoe -/- mice, yet had significantly higher triglycerides and weight gain over a 20-week period of HFD. Further investigation demonstrated treml1 -/- mice to have higher cholesterol than wild type mice (wt), suggesting the treml1 mutation contributes to the phenotype observed in DKO mice. Glucose evaluation of treml1 -/- , treml1 +/- and wt mice, showed a significant difference in basal glucose, and in plasma glucose clearance, as revealed by intraperitoneal (IP) glucose tolerance test. Analysis of serum insulin by ELISA showed no differences, while IP insulin tolerance test revealed treml1 -/- and treml1 +/- mice present apparent insulin hypersensitivity, as represented by the steady glucose decline 15 min post injection, with no recovery after two hours. Western blot performed in various tissues, demonstrated the presence of a TLT-1 splice variant that lacks the extracellular domain (TLT-1s), in the adipose tissue of treml1 -/- but not wt mice. Analysis of insulin response, in vivo by insulin sensitivity assay and in vitro using TSA 201 cells transfected with TLT-1s to determine the effect on AKT activation, revealed enhanced phosphorylation in the presence of TLT-1, with a similar response observed in vitro. This data support a model where TLT-1s modulation of AKT phosphorylation, increases adipocyte glucose uptake, leading to: low blood glucose levels, increased fatty acid production and storage, and the obese phenotype we observed in our mice.