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Fulltext Palmitic acid in the sn-2 position of dietary triacylglycerols does not affect insulin secretion or glucose homeostasis in healthy men and women

Filippou A, Teng KT, Berry SE, Sanders TA

Eur J Clin Nutr, 2014 Sep;68(9):1036-41.
PMID: 25052227 DOI: 10.1038/ejcn.2014.141

BACKGROUND/OBJECTIVES: Dietary triacylglycerols containing palmitic acid in the sn-2 position might impair insulin release and increase plasma glucose.
SUBJECTS/METHODS: We used a cross-over designed feeding trial in 53 healthy Asian men and women (20-50 years) to test this hypothesis by exchanging 20% energy of palm olein (PO; control) with randomly interesterified PO (IPO) or high oleic acid sunflower oil (HOS). After a 2-week run-in period on PO, participants were fed PO, IPO and HOS for 6 week consecutively in randomly allocated sequences. Fasting (midpoint and endpoint) and postprandial blood at the endpoint following a test meal (3.54 MJ, 14 g protein, 85 g carbohydrate and 50 g fat as PO) were collected for the measurement of C-peptide, insulin, glucose, plasma glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, lipids and apolipoproteins; pre-specified primary and secondary outcomes were postprandial changes in C-peptide and plasma glucose.
RESULTS: Low density lipoprotein cholesterol was 0.3 mmol/l (95% confidence interval (95% CI)) 0.1, 0.5; P<0.001) lower on HOS than on PO or IPO as predicted, indicating good compliance to the dietary intervention. There were no significant differences (P=0.58) between diets among the 10 male and 31 female completers in the incremental area under the curve (0-2 h) for C-peptide in nmol.120 min/l: GM (95% CI) were PO 220 (196, 245), IPO 212 (190, 235) and HOS 224 (204, 244). Plasma glucose was 8% lower at 2 h on IPO vs PO and HOS (both P<0.05).
CONCLUSION: Palmitic acid in the sn-2 position does not adversely impair insulin secretion and glucose homeostasis.

Matched MeSH terms: Blood Glucose/metabolism*
Fulltext Gastrointestinal metabolic surgery for the treatment of type 2 diabetes mellitus

Pok EH, Lee WJ

World J Gastroenterol, 2014 Oct 21;20(39):14315-28.
PMID: 25339819 DOI: 10.3748/wjg.v20.i39.14315

Medical therapy for type 2 diabetes mellitus is ineffective in the long term due to the progressive nature of the disease, which requires increasing medication doses and polypharmacy. Conversely, bariatric surgery has emerged as a cost-effective strategy for obese diabetic individuals; it has low complication rates and results in durable weight loss, glycemic control and improvements in the quality of life, obesity-related co-morbidity and overall survival. The finding that glucose homeostasis can be achieved with a weight loss-independent mechanism immediately after bariatric surgery, especially gastric bypass, has led to the paradigm of metabolic surgery. However, the primary focus of metabolic surgery is the alteration of the physio-anatomy of the gastrointestinal tract to achieve glycemic control, metabolic control and cardio-metabolic risk reduction. To date, metabolic surgery is still not well defined, as it is used most frequently for less obese patients with poorly controlled diabetes. The mechanism of glycemic control is still incompletely understood. Published research findings on metabolic surgery are promising, but many aspects still need to be defined. This paper examines the proposed mechanism of diabetes remission, the efficacy of different types of metabolic procedures, the durability of glucose control, and the risks and complications associated with this procedure. We propose a tailored approach for the selection of the ideal metabolic procedure for different groups of patients, considering the indications and prognostic factors for diabetes remission.

Matched MeSH terms: Blood Glucose/metabolism*
Role of nitric oxide in skeletal muscle glucose uptake during exercise

Hong YH, Betik AC, McConell GK

Exp Physiol, 2014 Dec 1;99(12):1569-73.
PMID: 25192731 DOI: 10.1113/expphysiol.2014.079202

Nitric oxide is produced within skeletal muscle fibres and has various functions in skeletal muscle. There is evidence that NO may be essential for normal increases in skeletal muscle glucose uptake during contraction/exercise. Although there have been some discrepant results, it has been consistently demonstrated that inhibition of NO synthase (NOS) attenuates the increase in skeletal muscle glucose uptake during contraction in mouse and rat muscle ex vivo, during in situ contraction in rats and during exercise in humans. The NO-mediated increase in skeletal muscle glucose uptake during contraction/exercise is probably due to the modulation of intramuscular signalling that ultimately increases glucose transporter 4 (GLUT4) translocation and is, surprisingly, independent of blood flow. In this review, we discuss the evidence for and against a role of NO in regulating skeletal muscle glucose uptake during contraction/exercise and outline the possible mechanism(s) involved. Emerging findings regarding the role of neuronal NOS mu (nNOSμ) in this process are also discussed.

Matched MeSH terms: Glucose/metabolism*
Fulltext Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-κB pathways

Bakar MH, Sarmidi MR, Kai CK, Huri HZ, Yaakob H

Int J Mol Sci, 2014 Dec 02;15(12):22227-57.
PMID: 25474091 DOI: 10.3390/ijms151222227

A growing body of evidence suggests that activation of nuclear factor kappa B (NF-κB) signaling pathways is among the inflammatory mechanism involved in the development of insulin resistance and chronic low-grade inflammation in adipose tissues derived from obese animal and human subjects. Nevertheless, little is known about the roles of NF-κB pathways in regulating mitochondrial function of the adipose tissues. In the present study, we sought to investigate the direct effects of celastrol (potent NF-κB inhibitor) upon mitochondrial dysfunction-induced insulin resistance in 3T3-L1 adipocytes. Celastrol ameliorates mitochondrial dysfunction by altering mitochondrial fusion and fission in adipocytes. The levels of oxidative DNA damage, protein carbonylation and lipid peroxidation were down-regulated. Further, the morphology and quantification of intracellular lipid droplets revealed the decrease of intracellular lipid accumulation with reduced lipolysis. Moreover, massive production of the pro-inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were markedly depleted. Insulin-stimulated glucose uptake activity was restored with the enhancement of insulin signaling pathways. This study signified that the treatments modulated towards knockdown of NF-κB transcription factor may counteract these metabolic insults exacerbated in our model of synergy between mitochondrial dysfunction and inflammation. These results demonstrate for the first time that NF-κB inhibition modulates mitochondrial dysfunction induced insulin resistance in 3T3-L1 adipocytes.

Matched MeSH terms: Glucose/metabolism
Fulltext Vernonia amygdalina simultaneously suppresses gluconeogenesis and potentiates glucose oxidation via the pentose phosphate pathway in streptozotocin-induced diabetic rats

Atangwho IJ, Yin KB, Umar MI, Ahmad M, Asmawi MZ

BMC Complement Altern Med, 2014;14:426.
PMID: 25358757 DOI: 10.1186/1472-6882-14-426

This study evaluated the impact of Vernonia amygdalina (VA) on the transcription of key enzymes involved in cellular modulation of glucose in streptozotocin-induced diabetic rats in a bid to understand the possible anti-diabetic mechanism of VA.

Matched MeSH terms: Blood Glucose/metabolism; Glucose/metabolism*
Fulltext Impact of ellagic acid in bone formation after tooth extraction: an experimental study on diabetic rats

Al-Obaidi MM, Al-Bayaty FH, Al Batran R, Hussaini J, Khor GH

ScientificWorldJournal, 2014;2014:908098.
PMID: 25485304 DOI: 10.1155/2014/908098

To estimate the impact of ellagic acid (EA) towards healing tooth socket in diabetic animals, after tooth extraction.

Matched MeSH terms: Blood Glucose/metabolism
Fulltext Chlorophytum borivilianum (Safed Musli) root extract prevents impairment in characteristics and elevation of oxidative stress in sperm of streptozotocin-induced adult male diabetic Wistar rats

Giribabu N, Kumar KE, Rekha SS, Muniandy S, Salleh N

BMC Complement Altern Med, 2014;14:291.
PMID: 25104050 DOI: 10.1186/1472-6882-14-291

We hypothesized that C. borivilianum root, known to improve male reproductive performance, prevents impairment in characteristics, morphology and elevation of oxidative stress in sperm of diabetics. We therefore investigated the effect of aqueous root extract of C. borivilianum on these parameters in diabetic rat model.

Matched MeSH terms: Blood Glucose/metabolism
Fulltext Leucaena leucocephala fruit aqueous extract stimulates adipogenesis, lipolysis, and glucose uptake in primary rat adipocytes

Kuppusamy UR, Arumugam B, Azaman N, Jen Wai C

ScientificWorldJournal, 2014;2014:737263.
PMID: 25180205 DOI: 10.1155/2014/737263

Leucaena leucocephala had been traditionally used to treat diabetes. The present study was designed to evaluate in vitro "insulin-like" activities of Leucaena leucocephala (Lam.) deWit. aqueous fruit extract on lipid and glucose metabolisms. The ability of the extract to stimulate adipogenesis, inhibit lipolysis, and activate radio-labeled glucose uptake was assessed using primary rat adipocytes. Quantitative Real-Time RT-PCR was performed to investigate effects of the extract on expression levels of genes (protein kinases B, AKT; glucose transporter 4, GLUT4; hormone sensitive lipase, HSL; phosphatidylinositol-3-kinases, PI3KA; sterol regulatory element binding factor 1, Srebp1) involved in insulin-induced signaling pathways. L. leucocephala aqueous fruit extract stimulated moderate adipogenesis and glucose uptake into adipocytes when compared to insulin. Generally, the extract exerted a considerable level of lipolytic effect at lower concentration but decreased gradually at higher concentration. The findings concurred with RT-PCR analysis. The expressions of GLUT4 and HSL genes were upregulated by twofold and onefold, respectively, whereas AKT, PI3KA, and Srebp1 genes were downregulated. The L. leucocephala aqueous fruit extract may be potentially used as an adjuvant in the treatment of Type 2 diabetes mellitus and weight management due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.

Matched MeSH terms: Glucose/metabolism
Fulltext Repeated batch fermentation biotechnology for the biosynthesis of lipid and gamma-linolenic acid by Cunninghamella bainieri 2A1

Ganjali Dashti M, Abdeshahian P, Wan Yusoff WM, Kalil MS, Abdul Hamid A

Biomed Res Int, 2014;2014:831783.
PMID: 25147817 DOI: 10.1155/2014/831783

The biosynthesis of biomedical products including lipid and gamma-linolenic acid (GLA) by Cunninghamella bainieri 2A1 was studied in repeated batch fermentation. Three key process variables, namely, glucose concentration, ammonium tartrate concentration, and harvesting time, were optimized using response surface methodology. Repeated batch fermentation was carried out by the cultivation of Cunninghamella bainieri 2A1 in nitrogen-limited medium with various nitrogen concentration (1-4 g/L) and glucose concentration (20-40 g/L) at three time intervals (12 h, 24 h, and 48 h). Experimental results showed that the highest lipid concentration of 6.2 g/L and the highest GLA concentration of 0.4 g/L were obtained in optimum conditions, where 20.2 g/L glucose, 2.12 g/L ammonium tartrate, and 48 h harvesting time were utilized. Statistical results showed that the interaction between glucose and ammonium tartrate concentration had highly significant effects on lipid and GLA biosynthesis (P < 0.01). Moreover, harvesting time had a significant interaction effect with glucose and ammonium tartrate concentration on lipid production (P < 0.05).

Matched MeSH terms: Glucose/metabolism
Fulltext Engineered silybin nanoparticles educe efficient control in experimental diabetes

Das S, Roy P, Pal R, Auddy RG, Chakraborti AS, Mukherjee A

PLoS One, 2014;9(7):e101818.
PMID: 24991800 DOI: 10.1371/journal.pone.0101818

Silybin, is one imminent therapeutic for drug induced hepatotoxicity, human prostate adenocarcinoma and other degenerative organ diseases. Recent evidences suggest that silybin influences gluconeogenesis pathways favorably and is beneficial in the treatment of type 1 and type 2 diabetes. The compound however is constrained due to solubility (0.4 mg/mL) and bioavailabilty limitations. Appropriate nanoparticle design for silybin in biocompatible polymers was thus proposed as a probable solution for therapeutic inadequacy. New surface engineered biopolymeric nanoparticles with high silybin encapsulation efficiency of 92.11% and zeta potential of +21 mV were designed. Both the pure compound and the nanoparticles were evaluated in vivo for the first time in experimental diabetic conditions. Animal health recovered substantially and the blood glucose levels came down to near normal values after 28 days treatment schedule with the engineered nanoparticles. Restoration from hyperglycemic damage condition was traced to serum insulin regeneration. Serum insulin recovered from the streptozotocin induced pancreatic damage levels of 0.17 ± 0.01 µg/lit to 0.57 ± 0.11 µg/lit after nanoparticle treatment. Significant reduction in glycated hemoglobin level, and restoration of liver glycogen content were some of the other interesting observations. Engineered silybin nanoparticle assisted recovery in diabetic conditions was reasoned due to improved silybin dissolution, passive transport in nanoscale, and restoration of antioxidant status.

Matched MeSH terms: Blood Glucose/metabolism*
Fulltext Particulate size of microalgal biomass affects hydrolysate properties and bioethanol concentration

Harun R, Danquah MK, Thiruvenkadam S

Biomed Res Int, 2014;2014:435631.
PMID: 24971327 DOI: 10.1155/2014/435631

Effective optimization of microalgae-to-bioethanol process systems hinges on an in-depth characterization of key process parameters relevant to the overall bioprocess engineering. One of the such important variables is the biomass particle size distribution and the effects on saccharification levels and bioethanol titres. This study examined the effects of three different microalgal biomass particle size ranges, 35 μm ≤ x ≤ 90 μm, 125 μm ≤ x ≤ 180 μm, and 295 μm ≤ x ≤ 425 μm, on the degree of enzymatic hydrolysis and bioethanol production. Two scenarios were investigated: single enzyme hydrolysis (cellulase) and double enzyme hydrolysis (cellulase and cellobiase). The glucose yield from biomass in the smallest particle size range (35 μm ≤ x ≤ 90 μm) was the highest, 134.73 mg glucose/g algae, while the yield from biomass in the larger particle size range (295 μm ≤ x ≤ 425 μm) was 75.45 mg glucose/g algae. A similar trend was observed for bioethanol yield, with the highest yield of 0.47 g EtOH/g glucose obtained from biomass in the smallest particle size range. The results have shown that the microalgal biomass particle size has a significant effect on enzymatic hydrolysis and bioethanol yield.

Matched MeSH terms: Glucose/metabolism
Fulltext Caprine pancreatic islet xenotransplantation into diabetic immunosuppressed BALB/c mice

Hani H, Allaudin ZN, Mohd-Lila MA, Ibrahim TA, Othman AM

Xenotransplantation, 2014 Mar-Apr;21(2):174-82.
PMID: 24645790 DOI: 10.1111/xen.12087

BACKGROUND: Type 1 diabetes mellitus is a devastating disease for which there is currently no cure, but only lifetime management. Islet xenotransplantation is a promising technique for the restoration of blood glucose control in patients with diabetes mellitus. The purpose of this study was to explore the potential use of caprine (goat) islet cells as xenogeneic grafts in the treatment for diabetes in a mouse model.
METHODS: Caprine pancreases were harvested and transported to the laboratory under conditions optimized to prevent ischemia. Islets were isolated, purified, and tested for functionality. Caprine islets (2000 islet equivalent) were transplanted beneath the kidney capsules of diabetic BALB/c mice under thalidomide-induced immunosuppression. Blood glucose and insulin levels of grafted mice were evaluated by glucometer and enzyme-linked immunosorbent assay kit, respectively. The functionality and quality of caprine pancreatic islet grafts were assessed by intraperitoneal glucose tolerance tests.
RESULTS: The viability of purified islet cells exceeded 90%. Recipient mice exhibited normoglycemia (<11 mM glucose) for 30 days. In addition, weight gain negatively correlated with blood glucose level. The findings verified diabetes reversal in caprine islet recipient mice. A significant drop in non-fasting blood glucose level (from 23.3 ± 5.4 to 8.04 ± 0.44 mM) and simultaneous increase in serum insulin level (from 0.01 ± 0.001 to 0.56 ± 0.17 μg/l) and body weights (from 23.64 ± 0.31 to 25.85 ± 0.34 g) were observed (P < 0.05). Immunohistochemical analysis verified insulin production in the transplanted islets.
CONCLUSIONS: Purified caprine islets were demonstrated to successfully sustain viability and functionality for controlling blood glucose levels in an immunosuppressed mouse model of diabetes. These results suggest the use of caprine islets as an addition to the supply of xenogeneic islets for diabetes research.
KEYWORDS: caprine islets; streptozotocin‐injected mice; type 1 diabetes; xenotransplantation

Matched MeSH terms: Blood Glucose/metabolism*
Fulltext Insulin resistance using HOMA model in obstructive sleep apnea: a cross sectional study

Azman M, Sani A, Kamaruddin NA

Ann Saudi Med, 2014;34(6):476-81.
PMID: 25971819 DOI: 10.5144/0256-4947.2014.476

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea (OSA) is a common disease affecting middle-aged patients and is associated with significant cardiovascular, cerebrovascular, and metabolic complications. Current evidences show inconclusive association between OSA and insulin resistance (IR). This study aims to examine the possible correlation between OSA parameters and IR.
DESIGN AND SETTINGS: This was a cross-sectional study to examine the association between OSA parameters and IR using homeostasis model assessment (HOMA) on patients who underwent polysomnogram (PSG) in a tertiary center between March 2011 and March 2012 (1 year).
PATIENTS AND METHODS: A total of 62 patients underwent PSG within the study period, of which 16 patients were excluded due to abnormal fasting blood sugar. Information on patients' medical illnesses, medications, and Epworth sleepiness scale (ESS) was obtained. Patients' body mass index (BMI), neck circumference, and waist circumference (WC) were measured. Blood samples were collected after 8 hours of fasting to measure HOMA-IR value. Overnight PSG was performed for all patients. Data was recorded and analyzed using SPSS, version 12.0 (SPSS Inc, Chicago, USA).
RESULTS: The prevalence of IR in OSA patients was 64.3%. There was significant correlation between OSA parameters (apnea-hypopnea index, ESS, BMI, and WC) and HOMA-IR with correlation coefficient of 0.529, 0.224, 0.261, and 0.354, respectively.
CONCLUSION: A linear correlation exists between OSA parameters and IR concluding a definite causal link between OSA and IR. IR screening is recommended in severe OSA patients.

Matched MeSH terms: Blood Glucose/metabolism*
Assessment of bioethanol yield by S. cerevisiae grown on oil palm residues: Monte Carlo simulation and sensitivity analysis

Samsudin MD, Mat Don M

Bioresour Technol, 2015 Jan;175:417-23.
PMID: 25459850 DOI: 10.1016/j.biortech.2014.10.116

Oil palm trunk (OPT) sap was utilized for growth and bioethanol production by Saccharomycescerevisiae with addition of palm oil mill effluent (POME) as nutrients supplier. Maximum yield (YP/S) was attained at 0.464g bioethanol/g glucose presence in the OPT sap-POME-based media. However, OPT sap and POME are heterogeneous in properties and fermentation performance might change if it is repeated. Contribution of parametric uncertainty analysis on bioethanol fermentation performance was then assessed using Monte Carlo simulation (stochastic variable) to determine probability distributions due to fluctuation and variation of kinetic model parameters. Results showed that based on 100,000 samples tested, the yield (YP/S) ranged 0.423-0.501g/g. Sensitivity analysis was also done to evaluate the impact of each kinetic parameter on the fermentation performance. It is found that bioethanol fermentation highly depend on growth of the tested yeast.

Matched MeSH terms: Glucose/metabolism
Increased risk of insulin resistance in rat offsprings exposed prenatally to white rice

Imam MU, Ismail M, Ooi DJ, Sarega N, Ishaka A

Mol Nutr Food Res, 2015 Jan;59(1):180-4.
PMID: 25329877 DOI: 10.1002/mnfr.201400396

White rice (WR) is a major staple food for people in developing countries and it may be responsible for the growing incidence of type 2 diabetes. Nonpregnant Female Sprague Dawley rats fed with WR or brown rice (BR) for 8 weeks were mated with age-matched male rats maintained on normal pellet over the same period. Offsprings were fed normal pellet after weaning until 8 weeks postdelivery. Rats fed with WR and their offsprings showed worsened oral glucose tolerance test, lower serum adiponectin levels, and higher weights, homeostatic model assessment of insulin resistance, serum retinol binding protein-4 levels, and leptin levels, compared with the normal and BR groups, suggesting an increased risk of insulin resistance. Furthermore, transcriptional levels of genes involved in insulin signaling showed different expression patterns in the liver, muscle, and adipose tissues of mothers and offsprings in both WR and BR groups. The results propose that the cycle of WR-induced insulin resistance in offsprings due to prenatal exposure, followed by their consumption of WR later in life may contribute to diabetes incidents. These findings are worth studying further.

Matched MeSH terms: Blood Glucose/metabolism
Quality of diabetes care in low- and middle-income Asian and Middle Eastern countries (1993-2012): 20-year systematic review

Shivashankar R, Kirk K, Kim WC, Rouse C, Tandon N, Narayan KM, et al.

Diabetes Res Clin Pract, 2015 Feb;107(2):203-23.
PMID: 25529849 DOI: 10.1016/j.diabres.2014.11.004

To assess the extent to which people with diabetes in low- and middle-income countries (LMIC) of Asia and the Middle East met evidence-based care recommendations through a systematic review of published literature.

Matched MeSH terms: Blood Glucose/metabolism
Cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and by stimulating insulin secretion in vitro

Hafizur RM, Hameed A, Shukrana M, Raza SA, Chishti S, Kabir N, et al.

Phytomedicine, 2015 Feb 15;22(2):297-300.
PMID: 25765836 DOI: 10.1016/j.phymed.2015.01.003

Although the anti-diabetic activity of cinnamic acid, a pure compound from cinnamon, has been reported but its mechanism(s) is not yet clear. The present study was designed to explore the possible mechanism(s) of anti-diabetic activity of cinnamic acid in in vitro and in vivo non-obese type 2 diabetic rats. Non-obese type 2 diabetes was developed by injecting 90 mg/kg streptozotocin in 2-day-old Wistar pups. Cinnamic acid and cinnamaldehyde were administered orally to diabetic rats for assessing acute blood glucose lowering effect and improvement of glucose tolerance. Additionally, insulin secretory activity of cinnamic acid and cinnamaldehyde was evaluated in isolated mice islets. Cinnamic acid, but not cinnamaldehyde, decreased blood glucose levels in diabetic rats in a time- and dose-dependent manner. Oral administration of cinnamic acid with 5 and 10 mg/kg doses to diabetic rats improved glucose tolerance in a dose-dependent manner. The improvement by 10 mg/kg cinnamic acid was comparable to that of standard drug glibenclamide (5 mg/kg). Further in vitro studies showed that cinnamaldehyde has little or no effect on glucose-stimulated insulin secretion; however, cinnamic acid significantly enhanced glucose-stimulated insulin secretion in isolated islets. In conclusion, it can be said that cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and stimulating insulin secretion in vitro.

Matched MeSH terms: Blood Glucose/metabolism
Vindogentianine, a hypoglycemic alkaloid from Catharanthus roseus (L.) G. Don (Apocynaceae)

Tiong SH, Looi CY, Arya A, Wong WF, Hazni H, Mustafa MR, et al.

Fitoterapia, 2015 Apr;102:182-8.
PMID: 25665941 DOI: 10.1016/j.fitote.2015.01.019

Vindogentianine, a new indole alkaloid together with six known alkaloids, vindoline, vindolidine, vindolicine, vindolinine, perivine and serpentine were isolated from leaf extract (DA) of Catharanthus roseus (L.) G. Don. Their structures were elucidated by spectroscopic methods; NMR, MS, UV and IR. Vindogentianine is a dimer containing a vindoline moiety coupled to a gentianine moiety. After 24h incubation, vindogentianine exhibited no cytotoxic effect in C2C12 mouse myoblast and β-TC6 mouse pancreatic cells (IC50>50μg/mL). Real-time cell proliferation monitoring also indicated vindogentianine had little or no effect on C2C12 mouse myoblast cell growth at the highest dose tested (200μg/mL), without inducing cell death. Vindogentianine exhibited potential hypoglycemic activity in β-TC6 and C2C12 cells by inducing higher glucose uptake and significant in vitro PTP-1B inhibition. However, in vitro α-amylase and α-glucosidase inhibition assay showed low inhibition under treatment of vindogentianine. This suggests that hypoglycemic activity of vindogentianine may be due to the enhancement of glucose uptake and PTP-1B inhibition, implying its therapeutic potential against type 2 diabetes.

Matched MeSH terms: Glucose/metabolism
Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function

Parker LM, Damanhuri HA, Fletcher SP, Goodchild AK

Brain Res, 2015 Apr 16;1604:25-34.
PMID: 25662772 DOI: 10.1016/j.brainres.2015.01.049

Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate.

Matched MeSH terms: Blood Glucose/metabolism; Glucose/metabolism*
Fulltext Glucose uptake during contraction in isolated skeletal muscles from neuronal nitric oxide synthase μ knockout mice

Hong YH, Frugier T, Zhang X, Murphy RM, Lynch GS, Betik AC, et al.

J Appl Physiol (1985), 2015 May 1;118(9):1113-21.
PMID: 25749441 DOI: 10.1152/japplphysiol.00056.2015

Inhibition of nitric oxide synthase (NOS) significantly attenuates the increase in skeletal muscle glucose uptake during contraction/exercise, and a greater attenuation is observed in individuals with Type 2 diabetes compared with healthy individuals. Therefore, NO appears to play an important role in mediating muscle glucose uptake during contraction. In this study, we investigated the involvement of neuronal NOSμ (nNOSμ), the main NOS isoform activated during contraction, on skeletal muscle glucose uptake during ex vivo contraction. Extensor digitorum longus muscles were isolated from nNOSμ(-/-) and nNOSμ(+/+) mice. Muscles were contracted ex vivo in a temperature-controlled (30°C) organ bath with or without the presence of the NOS inhibitor N(G)-monomethyl-l-arginine (L-NMMA) and the NOS substrate L-arginine. Glucose uptake was determined by radioactive tracers. Skeletal muscle glucose uptake increased approximately fourfold during contraction in muscles from both nNOSμ(-/-) and nNOSμ(+/+) mice. L-NMMA significantly attenuated the increase in muscle glucose uptake during contraction in both genotypes. This attenuation was reversed by L-arginine, suggesting that L-NMMA attenuated the increase in muscle glucose uptake during contraction by inhibiting NOS and not via a nonspecific effect of the inhibitor. Low levels of NOS activity (~4%) were detected in muscles from nNOSμ(-/-) mice, and there was no evidence of compensation from other NOS isoform or AMP-activated protein kinase which is also involved in mediating muscle glucose uptake during contraction. These results indicate that NO regulates skeletal muscle glucose uptake during ex vivo contraction independently of nNOSμ.

Matched MeSH terms: Glucose/metabolism*

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