Reduced Plasma Glucose Levels Research Articles

Hibiscus sabdariffa (ROSELLE) POLYPHENOL-RICH EXTRACT PREVENTS THE AORTIC OXIDATIVE DAMAGE IN TYPE 1 DIABETIC RATS

Diabetes mellitus complications mainly occur due to the oxidative stress-related condition. Thus, this study aimed to investigate the protective effect of the polyphenol-rich extract of Hibiscus sabdariffa (roselle) (HPE) on the aorta of streptozotocin-induced diabetic rats. Twenty-four male Sprague-Dawley rats were divided into four groups (n=6/group); non-diabetes control (NDM), diabetes (DM), diabetes treated with HPE (DM+HPE) and metformin (DM+MET). HPE and metformin were given orally at the dose of 100mg/kg and 150mg/kg respectively for eight weeks duration. At the end of the experiment period, blood pressure was measured before the rats were sacrificed. Blood was taken for measurement of plasma glucose and lipid levels whilst aorta was excised for oxidative stress and histological evaluation. Results showed that HPE treatment reduced plasma glucose level, blood pressure and improved dyslipidemia significantly (p<0.05) in DM+HPE group compared to DM group. Malondialdehyde (MDA) and advanced oxidation protein product (AOPP) levels were significantly decreased (p<0.05) while GSH level was significantly increased (p<0.05) in DM+HPE group compared to DM group. No histological changes observed in the aorta of all diabetic groups compared to NDM group. In conclusion, HPE might have a potential in minimizing the risk of vascular damage in diabetic conditions.

In Vivo Hypoglycemic Effect of Kigelia africana (Lam): Studies With Alloxan-Induced Diabetic Mice.

The claims by the traditional herbal medicine practitioners that Kigelia africana has bioactivity against several diseases, including diabetes mellitus, were investigated in this study. Type I diabetes mellitus was induced in mice by intraperitoneal administration of alloxan monohydrate followed by treatment with the therapeutic doses of the aqueous and ethyl acetate leaf extract of K africana to the experimentally diabetic mice. The treatment effects were compared with the normal control, diabetic control, and diabetic control rats treated with a standard antidiabetic drugs (insulin administered intraperitoneally at 1 IU/kg body weight in 0.1 mL physiological saline or glibenclamide administered orally at 3 mg/kg body weight in 0.1 mL physiological saline). Phytochemical composition of the leaf extract was assessed using standard procedures and mineral elements assessed using atomic absorption spectrophotometry and total reflection X-ray fluorescence system. Oral and intraperitoneal administration of the aqueous and ethyl acetate leaf extract caused a statistically significant dose-independent reduction in plasma glucose level in alloxan-induced diabetic mice. The observed hypoglycemic activity of this plant extract could be attributed to the observed phytochemicals and trace elements, which have been associated with exhibiting antidiabetic properties. Therefore, the data appear to support the hypoglycemic effects of K africana validating its folkloric usage.

Protective Effects of Dietary Flavonoids in Diabetic Induced Retinal Neurodegeneration.

Diabetic retinopathy is one of the serious complications of diabetes and the leading cause of decreased vision and blindness worldwide. Neurodegeneration has been recognized as initiating factor in causing the retinal damage, which leads to micro-vascular damage in diabetic retinopathy. Diabetes-induced oxidative stress is believed to be the key factor that damages neurons in the diabetic retina. Various therapeutic approaches for effective attenuation of increased oxidative stress by antioxidants have emerged. One such approach is to utilize dietary flavonoids, which have been found to possess powerful antioxidant activity. Some of the naturally occurring flavones possess anti-diabetic effects by enhancing insulin sensitivity and reducing plasma glucose levels in diabetic animal models. Considering the importance of developing new antioxidant compounds and the relevance of their applications in the treatment of diabetes and its complications, in this review article, we discuss and highlight various neuroprotective mechanisms of flavonoids in the diabetic retina. Dietary supplementation of flavonoids to diabetics may reduce oxidative stress, which in turn might ameliorate apoptosis and the levels of neurotrophic factors in the diabetic retina. This approach will elucidate a novel strategy for preventing and treating diabetic retinoneuropathy the leading cause of low vision and blindness.

The anti-inflammatory and anti-glycative effects of rosmarinic acid in the livers of type 1 diabetic mice.

Background: Rosmarinic acid (RA) is a polyphenol present in members of the Lamiaceae family. In this study, yhe anti-inflammatory and anti-glycative effects of RA in the livers of type 1 diabetic mice were examined.Methods: The diabetic mice were divided into three groups: diabetic mice with 0, low dose RA (25 mg/ml), and high dose RA (50 mg/ml). One group of non-diabetic mice was used as a control for comparison. RA was supplied via daily 200 μL oral injections for 9 weeks. The level of interleukin (IL)-6, the tumor necrosis factor (TNF)-alpha, the prostaglandin E2 (PGE2), and the activity of cyclooxygenase (COX)-2 in the livers were measured. The hepatic receptor of advanced glycative endproduct (RAGE), the sorbitol levels, and the glyoxalase 1 (GLO-1) activity were also determined.Results: Compared with diabetic group that received no RA, the groups with RA supplements at both levels of dosages had increased body weight and had both decreased water intake and feed intake (p < 0.05). RA intake was found to reduce plasma glucose level and elevate plasma insulin level when compared with the diabetic group that received no RA (p < 0.05). RA treatments lowered the hepatic level of IL-6, TNF-alpha, and PGE2, as well as the activity of COX-2 (p < 0.05). RA administration also decreased hepatic RAGE and sorbitol levels, and GLO-1 activity when compared with the diabetic group that received no RA (P < 0.05).Conclusion: These findings support the conclusion that rosmarinic acid (RA) could be a potent protective agent for the liver against diabetic injury.

Pair Feeding, but Not Insulin, Phloridzin, or Rosiglitazone Treatment, Curtails Markers of β-Cell Dedifferentiation in db/db Mice.

β-Cell failure is a hallmark of type 2 diabetes. Among several cellular biological mechanisms of cellular dysfunction, we and others have recently proposed that dedifferentiation of β-cells can explain the slowly progressive onset and partial reversibility of β-cell failure. Accordingly, we provided evidence of such processes in humans and experimental animal models of insulin-resistant diabetes. In this study, we asked whether β-cell dedifferentiation can be prevented with diet or pharmacological treatment of diabetes. db/db mice, a widely used model of insulin-resistant diabetes and obesity, were either pair fed or treated with the Sglt inhibitor phloridzin, the insulin-sensitizer rosiglitazone, or insulin. All treatments were equally efficacious in reducing plasma glucose levels. Pair feeding and phloridzin also resulted in significant weight loss. However, pair feeding among the four treatments resulted in a reduction of β-cell dedifferentiation, as assessed by Foxo1 and Aldh1a3 immunohistochemistry. The effect of diet to partly restore β-cell function is consistent with data in human diabetes and provides another potential mechanism by which lifestyle changes act as an effective intervention against diabetes progression.

In vivo antidiabetic activity of aqueous and ethyl acetate leaf extract of Senna singuena (Delile) in alloxan induced diabetic mice

The folkloric claims that Senna singuena confers antidiabetic effect to prescribed patients has received long term clinical application accompanied by limited scientific data in support of such claims. This study aimed at bioscreening for hypoglycemic activity of the aqueous and organic fractions of S. singuena in alloxan induced diabetic mice. Type I diabetes mellitus was induced in mice by intraperitoneal administration of alloxan monohydrate followed by graded doses of the aqueous and ethyl acetate leaf extract administered to the experimentally diabetic mice following an overnight fast. The composition of the various phytochemicals of the plant extract was quantitatively assessed using standard procedures. Oral and intraperitoneal administration of the aqueous and ethyl acetate leaf extract caused a significant reduction in plasma glucose level in a dose independent manner in both fractions. The hypoglycemic activity could be attributed to phytoconstituents found in the plant extract. The generated data supports the folkloric claims associating S. singuena with hypoglycemic effects. However, there is need for further studies on this plant to investigate the mechanism of its activity and determine its safety profiles in order to explore possibilities of developing a new antidiabetic drug.

Leptin replacement therapy restores endothelial function in mouse models of congenital and acquired lipodystrophy by reducing NOX‐1 and NOX‐4‐derived reactive oxygen species

Lipodystrophy is a congenital disorder or a condition acquired later in life characterized by a total or partial absence of adipose tissue resulting in drastic reductions in leptin levels, metabolic disorders and cardiovascular disease (CVD). In 2014 the Food and Drug Administration approved the use of leptin as a therapy to minimize the metabolic dysfunction developed by lipodystrophic patients. However, whether leptin replacement therapy improves lipodystrophy‐associated CVD remains unknown. Here, we tested the hypothesis that exogenous leptin restores vascular function in lipodystrophic mice by regulating redox signaling. Studies were conducted in 10–12 week‐old male Berardinelli‐Seip gene (gBscl2−/−) deficient mice, a well‐characterized model of congenital lipodystrophy, as well as in inducible Bscl2 deficient mice (iBscl2−/−), a model of acquired lipodystrophy. Reduction of adipose tissue in gBscl2−/− and iBscl2−/− mice was confirmed by nuclear magnetic resonance spectroscopy: [wild‐type (WT): 8.1 ± 0.3 vs gBlsc2−/− 1.9 ± 0.5* and iBscl2−/−: 4.2 ± 0.7* (%)*P&lt;0.05 vs WT]. Both gBscl2−/− and iBscl2−/− exhibit reduced plasma leptin levels, hyperglycemia, hyperinsulinemia and hyperlipidemia, indicative of metabolic dysfunction. Radio‐telemetry measurements did not report increases in blood pressure in lipodystrophic mice. Analysis of the aortic vascular reactivity via wire‐myography revealed a severe endothelial dysfunction in both gBscl2−/− and iBscl2−/−, characterized by an impaired relaxation to acetylcholine but no alteration of the endothelium‐independent relaxation (relaxation to sodium nitroprusside). Acute reactive oxygen species scavenging with the superoxide dismutase mimetic tempol (100 μmol/l) or the NOX1‐NOX4 inhibitor GKT137831 (10 μmol/l) restored endothelial function in aortic rings from both gBscl2−/− and iBscl2−/− mice. In parallel, quantitative real‐time RT‐PCR, revealed increases in Nox1 and Nox4 gene expression, as well as in the expression of the NADPH oxidase regulatory subunit NOXA1, in aortic rings from both gBscl2−/− and iBscl2−/− mice. To determine the role of leptin in the vascular dysfunction, gBscl2−/− and iBscl2−/− mice were submitted to a chronic leptin treatment (osmotic mini‐pump 10ug/mouse per day for 7 days). Restoration of leptin levels normalized glucose levels and did not affect the BP. Leptin replacement restored endothelial function and reduced Nox1 and Nox4 ‐ enzymes expression in the vasculature of gBscl2−/− mice. Similarly leptin reduced plasma glucose levels and improved endothelial function in iBscl2−/− mice as it reduced Nox‐enzyme expression. Taken together, these data demonstrate that leptin replacement therapy restored endothelial function in mouse models of congenital and acquired lipodystrophy, via reducing the expression of the ROS‐generating enzymes. These data also emphasize the physiological role of leptin in the control of metabolic and vascular function and may present leptin replacement therapy as a potential therapeutic avenue for the treatment of other metabolic disease such as type 1 diabetes.Support or Funding InformationThis work was supported by Innovative Research Grant from the American Heart Association (16IRG27770047 to EJ.BdC) and a R01 from the NHLBI (1R01HL130301‐01 to EJ.BdC).

Effect of oral protein hydrolysate on glucose control in patients with gestational diabetes

In type 2 diabetic patients, a casein-based protein hydrolysate has been shown to increase plasma insulin and to lower plasma glucose. In the present study, we examined the acute and prolonged effects of protein hydrolysate on postprandial glucose, insulin and C-peptide responses after a standardised breakfast and the effect on daily glucose control in patients with gestational diabetes. In a single-centre randomised double blind placebo controlled design, patients with mild gestational diabetes (no use of insulin or oral antidiabetic agents; n=26/group) were allocated to receive a protein hydrolysate drink, 8.5g before breakfast and 8.5g before dinner or a placebo drink which was identical to the protein hydrolysate drink in appearance and taste, yet lacked carbohydrate, fat or protein, for 8 days. Baseline characteristics including fasting levels of glucose, insulin, C-peptide and insulin-glucose ratio were similar between the groups. Compared to the placebo drink, neither the first dose of the proteinhydrolysate drink nor the final dose had effects on 4-harea under the curve for plasma levels of insulin and C-peptide, or the insulin-to-glucose ratio; however, plasma glucose was moderately lower between t=45, 60 and 75min. In addition, mean daily capillary glucose levels were lower in the protein hydrolysate group. Two patients in the PH drink group had to be withdrawn because of vomiting after the first dose. In patients with gestational diabetes, a twice-daily dose of 8.5g of protein hydrolysate of casein had no insulinotropic effects, but did moderately reduce plasma glucose levels, suggesting an increase in insulin sensitivity.

The Effect of OSA Therapy on Glucose Metabolism: It's All about CPAP Adherence!

The Effect of OSA Therapy on Glucose Metabolism: It's All about CPAP Adherence!

5-aminolevulinic acid combined with ferrous ion reduces adiposity and improves glucose tolerance in diet-induced obese mice via enhancing mitochondrial function

BackgroundMitochondrial dysfunction is associated with obesity and various obesity-associated pathological conditions including glucose intolerance. 5-Aminolevulinic acid (ALA), a precursor of heme metabolites, is a natural amino acid synthesized in the mitochondria, and various types of cytochromes containing heme contribute to aerobic energy metabolism. Thus, ALA might have beneficial effects on the reduction of adiposity and improvement of glucose tolerance through its promotion of heme synthesis. In the present study, we investigated the effects of ALA combined with sodium ferrous citrate (SFC) on obesity and glucose intolerance in diet-induced obese mice.MethodsWe used 20-weeks-old male C57BL/6J diet-induced obesity (DIO) mice that had been fed high-fat diet from 4th week or wild-type C57BL/6J mice. The DIO mice were orally administered ALA combined with SFC (ALA/SFC) for 6 weeks. At the 4th and 5th week during ALA/SFC administration, mice were fasted for 5 h and overnight, respectively and used for oral glucose tolerance test. After the ALA/SFC administration, the plasma glucose levels, weight of white adipose tissue, and expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes were examined. Furthermore, the effects of ALA/SFC on lipid content and glucose uptake were examined in vitro.ResultsOral administration of ALA/SFC for 6 weeks reduced the body weight by about 10% and the weight of white adipose tissues in these animals. In vitro, ALA/SFC reduced lipid content in mouse 3T3-L1 adipocytes in a dose dependent manner, and enhanced glucose uptake in 3T3-L1 adipocytes by 70–90% and rat L6 myoblasts by 30% at 6 h. Additionally, oral administration of ALA/SFC reduced plasma glucose levels and improved glucose tolerance in DIO mice. Furthermore, ALA/SFC enhanced the expression of OXPHOS complexes III, IV, and V by 40–70% in white adipose tissues of DIO mice, improving mitochondrial function.ConclusionsOur findings indicate that ALA/SFC is effective in the reduction of adiposity and improvement of glucose tolerance, and that the induction of mitochondrial OXPHOS complex III, IV, and V by ALA/SFC might be an essential component of the molecular mechanisms underlying these effects. ALA/SFC might be a useful supplement for obesity and obesity-related metabolic disease such as type 2 diabetes mellitus.

Archachatina marginata Haemolymph Potentiates Hypoglycemic Effect by Mimicking Insulin in Streptozotocin-Induced Diabetic Rat

Aims: This study investigates the hypoglycemic potential of Archachatina marginata haemolymph and its mechanism in streptozotocin -induced diabetic rats. Study Design: One factor experimental design. Place and Duration of Study: Department of Chemical Sciences, Joseph Ayo Babalola University, Ikeji Arakeji, Osun State, Nigeria between January to June, 2015. Methodology: The rats were set into four groups (n=5). Group 1 - Non-diabetic control (NDC), Group 2 - Diabetic Control (DC), Group 3 - Diabetic rats with 1 mL administration of snail Original Research Article Adeboye et al.; JPRI, 18(1): 1-8, 2017; Article no.JPRI.33786 2 haemolymph (DSS1), Group 4 - Diabetic rats with 2 mL snail haemolymph administration (DSS2). The blood glucose concentration of each rat was taken and thereafter, they were weighed and then administered with 55 mg/kg STZ in citrate buffer (pH 4.5) peritoneally non-diabetic control group (NDC). Rats with blood glucose level of 200 mg/dL and above were considered diabetic. Haemolymph of 1 mL and 2 mL were administered to rats in DSS1 and DSS2 respectively while DC received 2 mL distilled water for 14 consecutive days. Physiological orangs and blood samples were harvested for various analysis. Results: The A. marginata haemolymph significantly improved the plasma concentration of insulin and reduced plasma glucose level in a dose dependent manner P=.05. Conclusion: The A. marginata haemolymph has potential to exact hypoglycemic effect and improve the insulin concentration in streptozotocin induced diabetic rat. Keywords: Archachatina marginata; haemolymph; streptozocin diabetes rats.

Improved systemic delivery of insulin by condensed drug loading in a dimpled suppository.

The development of peptide therapeutics owing to the advances in biotechnology has overcome some unmet medical needs; however, the route of administration is still limited to injections. Systemic delivery of insulin via an enteral route remains a great challenge due to its instability and low mucosal permeability. In this study, we investigated the effect of drug condensation in a suppository on the efficacy of insulin after rectal administration. Suppositories with dimples are prepared by a mold method using a hard fat (Suppocire® AM). Insulin or fluorescein isothiocyanate-dextran (molecular weight: 3,000-5,000) (FD4) as a model of a hydrophilic macromolecule was loaded in the dimples, and sealed with other lipids with different melting points. The in vitro release test showed that the time to 50% drug release depends on the melting point of the lipid for sealing but not on the number of dimples. The suppositories with one-, or three-dimple containing insulin and caprylocaproyl macrogol-8 glyceride (Labrasol®) were administered to rats at 0.5 U/head. The reduction in plasma glucose level was more significant for the one-dimple-type suppository than for the three-dimple-type although the one-dimple-type suppository contained less amount of Labrasol by one-third compared to the three-dimple-type. These results suggest that condensation of an insulin dose in a limited surface area of a suppository improves systemic availability via the rectal route with a reduced amount of an absorption enhancer.

Novel Non-carboxylate Benzoylsulfonamide-Based Protein Tyrosine Phosphatase 1B Inhibitors with Non-competitive Actions.

A novel series of benzoylsulfonamide derivatives were synthesized and biologically evaluated. Among them, 4-(biphenyl-4-ylmethylsulfanylmethyl)-N-(hexane-1-sulfonyl)benzamide (compound 18K) was identified as a protein tyrosine phosphatase 1B (PTP1B) inhibitor with potent and selective inhibitory activity against PTP1B (IC50=0.25 µM). Compound 18K functioned as a non-competitive inhibitor and bound to the allosteric site of PTP1B. It also showed high oral absorption in mice (the maximum drug concentration (Cmax)=45.5 µM at 30 mg/kg), rats (Cmax=53.6 µM at 30 mg/kg), and beagles (Cmax=37.8 µM at 10 mg/kg), and significantly reduced plasma glucose levels at 30 mg/kg/d (per os (p.o.)) for one week with no side effects in db/db mice. In conclusion, the substituted benzoylsulfonamide was shown to be a novel scaffold of a non-competitive and allosteric PTP1B inhibitor, and compound 18K has potential as an efficacious and safe anti-diabetic drug as well as a useful tool for investigations of the physiological and pathophysiological effects of allosteric PTP1B inhibition.

Dapagliflozin- Induced Severe Ketoacidosis Requiring Hemodialysis

The availability of novel classes of medication for the treatment of type 2 Diabetes mellitus (type 2 DM) provides doctors with options to choose individualized treatments based on patient and agent characteristics beyond metformin therapy, as per current guidelines. Independent of impaired beta-cell function and insulin resistance, sodium glucose cotransporter type 2 (SGLT2) inhibitors represent a different treatment strategy for reducing plasma glucose levels and glycosylated hemoglobin concentrations by increasing urinary glucose excretion through reduced renal glucose reabsorption. However, metabolic acidosis may arise with such novel drugs through a different mechanism, which can produce a life-threatening condition requiring hemodialysis.

Neuroprotective effects of potassium channel openers on cerebral ischemia–reperfusion injury in diabetic rats

ObjectivesThis study was done to estimate the potential neuroprotective role of potassium channel openers in cerebral ischemia–reperfusion (IR) injury in streptozotocin (STZ) induced type-I diabetic rats (T1DR). MethodsPotassium channel openers – cromakalim, cinnarizine and nicorandil; potassium channel blocker –glibenclamide, insulin (as an antidiabetic standard), telmisartan (as an anti-hypertensive standard agent) and vitamin E (as an antioxidant and antiapoptotic standard agent) were given for 3days in streptozotocin (45mg/kg i.v.) induced type I diabetic rats along with middle cerebral artery occlusion. After 24h of surgery, plasma glucose, neurobehavioral score, cerebral infarct volume, blood pressure and caspase-3 levels were measured to evaluate the mechanism of potassium channel openers (KCOs) for neuroprotection. ResultsFollowing STZ administration and ischemia–reperfusion, blood sugar, neurobehavioral score, cerebral infarct volume and caspase-3 levels were significantly high in diabetic-IR groups. Treatment with cromakalim, cinnarizine, nicorandil, insulin and vitamin E significantly reduce neurobehavioral score while nicorandil and vitamin E significantly reduced cerebral infarct volume. Caspase-3 levels were significantly reduced by cromakalim and nicorandil treated animals. Except insulin and glibenclamide, none of the agents significantly reduce plasma glucose levels. ConclusionTreatment of ischemic stroke with potassium channel openers in T1DR is neuroprotective. Inhibition of apoptosis may contribute to their neuroprotective effects after stroke in T1DR.

Antidiabetic activity of Chandraprabha vati – A classical Ayurvedic formulation

BackgroundChandraprabha vati is a classical Ayurvedic formulation, markedly used for mitigation of Prameha, which correlates in many ways with obesity, metabolic syndrome and diabetes mellitus. ObjectiveThe present study was aimed to investigate effect of Chandraprabha vati in experimentally-induced hyperglycemia and lipid profile alterations. Materials and methodsAntidiabetic effect of Chandraprabha vati was studied in fifty five Wistar rats. Graded doses of Chandraprabha vati (50, 100 and 200 mg/kg) were administered orally for 7 days to normal and alloxan-hyperglycemic rats (65 mg/kg, intravenously), and to glucose loaded normal rats for oral glucose tolerance test (OGTT). Fasting plasma glucose levels were assessed on different time intervals along with plasma cholesterol and triglycerides. Metformin (500 mg/kg, orally) was used as standard drug. ResultsChandraprabha vati did not cause any significant reduction in plasma glucose levels of normal rats (p > 0.05) but normalized the impaired glucose tolerance at 60 and 120 min (p < 0.05–p < 0.001) in OGTT when compared to vehicle control. In alloxan-hyperglycemic rats, administration of Chandraprabha vati (200 mg/kg) significantly reduced plasma glucose at 3 h, 12 h, 3rd day and 7th day (p < 0.01–p < 0.001) along with reduction in cholesterol and triglycerides levels (p < 0.01–p < 0.001) when compared to diabetic control group. The effects were comparable with metformin. ConclusionsChandraprabha vati exhibited anti-hyperglycemic effect and attenuated alterations in lipid profile. The results support the use of Chandraprabha vati for correction of Prameha in clinical practice.

Distinct clinical characteristics and therapeutic modalities for diabetic ketoacidosis in type 1 and type 2 diabetes mellitus

AimsPatients with type 1 diabetes often develop diabetic ketoacidosis (DKA). Reportedly, DKA in type 2 diabetes has higher mortality despite its limited occurrence. The exact clinical characteristics and therapeutic modalities yielding successful outcomes in DKA type 2 diabetes remain unknown. MethodsThis retrospective study compared the clinical features and detailed treatment of consecutive type 1 and type 2 diabetes patients hospitalized with DKA between January 2001 and December 2014. ResultsWe report on 127 patients with type 1 and 74 patients with type 2 diabetes whose DKA was successfully treated. The most frequent precipitating cause for DKA was infectious disease for patients with type 1 diabetes and consumption of sugar-containing beverages for those with type 2 diabetes. Type 2 diabetes patients showed higher mean plasma glucose levels than those with type 1 diabetes (48.4±21.6, vs. 37.1±16.4mmol/l, P<0.01) and higher serum creatinine, blood urea nitrogen, and hemoglobin levels, which normalized after DKA resolution. Compared with type 1 diabetes patients, those with type 2 diabetes required distinctly higher daily total insulin dosage (35.9±37.0U, vs. 20.2±23.3U, P<0.01), larger replacement fluid volumes (4.17±2.69L, vs. 2.29±1.57L, P<0.01) and greater potassium supplementation (23.9±36.5mEq, vs. 11.2±17.9mEq, P<0.01) to resolve DKA and reduce plasma glucose level to ≤16.7mmol/l. ConclusionsDKA patients with type 2 diabetes required management with a modified treatment protocol to resolve their profound hyperglycemia and dehydration compared with those with type 1 diabetes.

Oral treatment with a zinc complex of acetylsalicylic acid prevents diabetic cardiomyopathy in a rat model of type-2 diabetes: activation of the Akt pathway.

BackgroundType-2 diabetics have an increased risk of cardiomyopathy, and heart failure is a major cause of death among these patients. Growing evidence indicates that proinflammatory cytokines may induce the development of insulin resistance, and that anti-inflammatory medications may reverse this process. We investigated the effects of the oral administration of zinc and acetylsalicylic acid, in the form of bis(aspirinato)zinc(II)-complex Zn(ASA)2, on different aspects of cardiac damage in Zucker diabetic fatty (ZDF) rats, an experimental model of type-2 diabetic cardiomyopathy.MethodsNondiabetic control (ZL) and ZDF rats were treated orally with vehicle or Zn(ASA)2 for 24 days. At the age of 29–30 weeks, the electrical activities, left-ventricular functional parameters and left-ventricular wall thicknesses were assessed. Nitrotyrosine immunohistochemistry, TUNEL-assay, and hematoxylin-eosin staining were performed. The protein expression of the insulin-receptor and PI3K/AKT pathway were quantified by Western blot.ResultsZn(ASA)2-treatment significantly decreased plasma glucose concentration in ZDF rats (39.0 ± 3.6 vs 49.4 ± 2.8 mM, P < 0.05) while serum insulin-levels were similar among the groups. Data from cardiac catheterization showed that Zn(ASA)2 normalized the increased left-ventricular diastolic stiffness (end-diastolic pressure–volume relationship: 0.064 ± 0.008 vs 0.084 ± 0.014 mmHg/µl; end-diastolic pressure: 6.5 ± 0.6 vs 7.9 ± 0.7 mmHg, P < 0.05). Furthermore, ECG-recordings revealed a restoration of prolonged QT-intervals (63 ± 3 vs 83 ± 4 ms, P < 0.05) with Zn(ASA)2. Left-ventricular wall thickness, assessed by echocardiography, did not differ among the groups. However histological examination revealed an increase in the cardiomyocytes’ transverse cross-section area in ZDF compared to the ZL rats, which was significantly decreased after Zn(ASA)2-treatment. Additionally, a significant fibrotic remodeling was observed in the diabetic rats compared to ZL rats, and Zn(ASA)2-administered ZDF rats showed a similar collagen content as ZL animals. In diabetic hearts Zn(ASA)2 significantly decreased DNA-fragmentation, and nitro-oxidative stress, and up-regulated myocardial phosphorylated-AKT/AKT protein expression. Zn(ASA)2 reduced cardiomyocyte death in a cellular model of oxidative stress. Zn(ASA)2 had no effects on altered myocardial CD36, GLUT-4, and PI3K protein expression.ConclusionsWe demonstrated that treatment of type-2 diabetic rats with Zn(ASA)2 reduced plasma glucose-levels and prevented diabetic cardiomyopathy. The increased myocardial AKT activation could, in part, help to explain the cardioprotective effects of Zn(ASA)2. The oral administration of Zn(ASA)2 may have therapeutic potential, aiming to prevent/treat cardiac complications in type-2 diabetic patients.

Sitagliptin monotherapy has better effect on insulinogenic index than glimepiride monotherapy in Japanese patients with type 2 diabetes mellitus: a 52-week, multicenter, parallel-group randomized controlled trial

BackgroundThe 52-week monotherapy with the dipeptidyl peptidase-4 inhibitor sitagliptin and the sulphonylurea glimepiride on early-phase insulin secretion in Japanese patients with type 2 diabetes mellitus (T2DM) is not known.MethodsA randomized, parallel-group, open-label trial was conducted at 18 centers between February, 2011 and March, 2013. 171 outpatients with T2DM were recruited and randomly assigned to glimepiride or sitagliptin by minimization. Doses of glimepiride (0.25–1.0 mg/day) and sitagliptin (25–100 mg/day) were adjusted for hemoglobin A1c (HbA1c) > 6.9 %. Analyses were performed on full analysis set (FAS) of randomized subjects taking medications as allocated, and underwent 75 g oral glucose tolerance test (OGTTs) before and after treatment. The primary outcome was insulinogenic index to quantify early-phase insulin secretion after treatment, which was evaluated by analysis of covariance (ANCOVA).ResultsOf 171 enrolled subjects, 68 in the sitagliptin group and 65 in the glimepiride group were included in the FAS (mean age, 64 years; baseline (HbA1c), 7.4 %). The primary outcome revealed a significantly higher insulinogenic index in the sitagliptin group than that in the glimepiride group (p = 0.036). Sitagliptin also reduced plasma glucose levels at 60 and 120 min during OGTT compared with glimepiride, while achieving a similar improvement in HbA1c during treatment. Body weight did not change in either of the two groups, and one case of hypoglycemia was observed in the glimepiride group.ConclusionsSitagliptin shows better effects on insulinogenic index after 52-week treatment compared with glimepiride in Japanese patients with T2DM.Trial registration University hospital Medical Information Network (UMIN) Clinical Trials Registry, No.00004791.Electronic supplementary materialThe online version of this article (doi:10.1186/s13098-016-0131-y) contains supplementary material, which is available to authorized users.

Antidiabetic Effect of Sargassum wightii and Ulva fasciata in High fat diet and Multi Low Dose Streptozotocin Induced Type 2 Diabetic Mice

This study was undertaken to evaluate the antidiabetic effect of edible seaweeds Sargassum wightii and Ulva fasciata with an objective to establish these seaweeds as add-on therapy for controlling diabetes. The ethyl acetate extract of Sargassum wightii (EAS) and Ulva fasciata (EAU) at 100 and 200 mg/kg dose was examined for antidiabetic activity in the high fat diet and multi-low-dose streptozotocin induced type 2 diabetic mice. Plasma glucose, oral glucose tolerance test [OGTT], lipid profile, liver and skeletal muscle glycogen content, triglycerides, superoxide dismutase [SOD], body and organ weight was estimated at the end of the study. Consequently, histopathology of liver was also studied. Both EAS and EAU showed significant reduction in plasma glucose level and the area under curve [AUC] of OGTT was significantly (p&lt;0.001) attenuated. The extracts appreciably normalized lipid profile, body and organ weight. At higher doses of both EAS and EAU showed significant (p&lt;0.05) improvement in SOD level of skeletal muscle and reduction in liver as well as skeletal muscle triglycerides. Both the extracts considerably enhanced hepatic and muscle glycogen content. Remarkable improvements were found in the histopathological observations of liver of all the treated groups as compared against the diabetes induced group. The findings suggest that these seaweeds offer a great opportunity to satisfy the food and nutrition requirement for rectifying and controlling diabetes.