ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Opuntia ficus-indica (L.) Mill is frequently observed in the Moroccan traditional medicinal system, where these approaches are employed to mitigate the onset of diabetes and the subsequent complications it may entail. AIM OF THE STUDY: The aim of this research was to examine the effectiveness of Opuntia ficus-indica seed oil in preventing diabetic complications. Specifically, the study assessed its ability to counteract glycation at various stages, protected red blood cells from the harmful effects of glycated albumin, and inhibited pancreatic lipase digestive enzymes to understand its potential antihyperglycemic properties. Additionally, the study aimed to identify the chemical components responsible for these effects, evaluate antioxidant and anti-inflammatory properties, and conduct computational investigations such as molecular docking. MATERIALS AND METHODS: The assessement of Opuntia ficus-indica seed oil antiglycation properties involved co-incubating the extract oil with a bovine serum albumin-glucose glycation model. The study investigated various stages of glycation, incorporating fructosamine (inceptive stage), protein carbonyls (intermediate stage), and AGEs (late stage). Additionally, measurement of ß-amyloid aggregation of albumin was performed using Congo red, which is specific to amyloid structures. Additionally, the evaluation of oil's safeguarding effect on erythrocytes against toxicity induced by glycated albumin included the measurement of erythrocyte hemolysis, lipid peroxidation, reduced glutathione. The fatty acid of Opuntia ficus-indica seed oil were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS). The in vitro evaluation of antihyperglycemic activity involved the use of pancreatic lipase enzyme, while the assessement of antioxidant capability was carried out through the utilization of the ABTS and FRAP methods. The in vitro assessement of the denaturation of albumin activity was also conducted. In conjunction with the experimental outcomes, computational investigations were undertaken, specifically employing ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. Furthermore, molecular docking was utilized to predict antioxidant and antiglycation mechanisms based on protein targets. RESULTS: In vitro glycation assays, Opuntia ficus-indica seed oil displayed targeted inhibitory effects at multiple distinct stages. Within erythrocytes, in addition to mitigating hemolysis and lipid peroxidation induced by glycated albumin. GC-MS investigation revealed a richness of fatty acids and the most abundant compounds are Linoleic acid (36.59%), Palmitic acid (20.84%) and Oleic acid (19.33%) respectively. The findings of antioxidant ability showed a remarkable activity on FRAP and ABTS radicals. This oil showed a pronounced inhibitory impact (p < 0.001) on pancreatic lipase enzyme. It also exerted a notibale inhibition of albumin denaturation, in vitro. CONCLUSION: The identified results were supported by the abundant compounds of fatty acids unveiled through GC-MS analysis, along with the computational investigation and molecular docking.
Subject(s)
Antioxidants , Erythrocytes , Fatty Acids , Gas Chromatography-Mass Spectrometry , Molecular Docking Simulation , Opuntia , Oxidative Stress , Plant Oils , Seeds , Opuntia/chemistry , Erythrocytes/drug effects , Erythrocytes/metabolism , Oxidative Stress/drug effects , Seeds/chemistry , Fatty Acids/chemistry , Morocco , Antioxidants/pharmacology , Antioxidants/chemistry , Plant Oils/pharmacology , Plant Oils/chemistry , Gas Chromatography-Mass Spectrometry/methods , Glycation End Products, Advanced/metabolism , Animals , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Lipase/antagonists & inhibitors , Lipase/metabolism , Glycosylation/drug effects , Glycated Serum Albumin , Humans , Serum Albumin, Bovine , Serum Albumin/metabolismABSTRACT
The interaction of drugs with human serum albumin (HSA) is an important element of therapy. Albumin affects the distribution of the drug substance in the body, as well as its pharmacokinetic and pharmacodynamic properties. On the one hand, inflammation and protein glycation, directly associated with many pathological conditions and old age, can cause structural and functional modification of HSA, causing binding disorders. On the other hand, the widespread availability of various dietary supplements that affect the content of fatty acids in the body means that knowledge of the binding activity of transporting proteins, especially in people with chronic diseases, e.g., diabetes, will achieve satisfactory results of the selected therapy. Therefore, the aim of the present study was to evaluate the effect of a mixture of fatty acids (FA) with different saturated and unsaturated acids on the affinity of acetohexamide (AH), a drug with hypoglycaemic activity for glycated albumin, simulating the state of diabetes in the body. Based on fluorescence studies, we can conclude that the presence of both saturated and unsaturated FA disturbs the binding of AH to glycated albumin. Acetohexamide binds more strongly to defatted albumin than to albumin in the presence of fatty acids. The competitive binding of AH and FA to albumin may influence the concentration of free drug fraction and thus its therapeutic effect.
Subject(s)
Acetohexamide/chemistry , Fatty Acids/chemistry , Hypoglycemic Agents/chemistry , Serum Albumin, Human/chemistry , Serum Albumin/chemistry , Binding, Competitive , Glucose/chemistry , Glycation End Products, Advanced , Humans , Linoleic Acid/chemistry , Molecular Dynamics Simulation , Myristic Acid/chemistry , Oleic Acid/chemistry , Palmitic Acid/chemistry , Protein Binding , Protein Conformation , Solutions , Glycated Serum AlbuminABSTRACT
SCOPE: In this study, we investigated the effect of aged garlic extract (AGE) on the high level of blood glucose in Tsumura Suzuki Obese-Diabetes (TSOD) mice. METHODS AND RESULTS: TSOD mice were fed standard diet with or without 2% AGE for 19 weeks. AGE treatment lowered the blood glucose level and significantly reduced the plasma level of glycated albumin in TSOD mice as compared with those without AGE treatment. In addition, AGE treatment increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the adipose tissue, liver and muscle that played an important role in the maintenance of insulin sensitivity. Moreover, AGE treatment also suppressed the mRNA expression of fatty acid synthase, a known factor regulated by AMPK, and monocyte chemoattractant protein 1, one of the representative inflammatory chemokines, in the adipose tissue but not in the liver. CONCLUSION: AGE treatment suppresses the increase of plasma glycated albumin level in TSOD mice and this effect is accompanied by the activation of AMPK in adipose tissue, and suggests that AGE may play a potential role in the prevention and treatment of type 2 diabetes.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Adipose Tissue/drug effects , Garlic/chemistry , Plant Extracts/pharmacology , Serum Albumin/metabolism , AMP-Activated Protein Kinases/genetics , Adipose Tissue/metabolism , Animals , Blood Glucose/metabolism , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diet , Fatty Acid Synthases/genetics , Fatty Acid Synthases/metabolism , Food Handling , Glycation End Products, Advanced , Insulin Resistance , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Obese , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Glycated Serum AlbuminABSTRACT
Although extracts of the roots and stems of Salacia chinensis have been used in folk medicines for chronic diseases such as rheumatism, irregular menstruation, asthma and diabetes mellitus, little is known about the mechanism by which Salacia chinensis extract (SCE) ameliorates these diseases. To clarify whether SCE ameliorates the progression of lifestyle-related diseases, the inhibitory effect of SCE on the formation of advanced glycation end products (AGEs) was analyzed in a rat model of streptozotocin-induced diabetes. Although the oral administration of SCE did not ameliorate the diabetes-induced decrease in body weight, it ameliorated the increase in glycoalbumin levels in diabetic rats. An analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS) demonstrated that the levels of N(ε)-(carboxymethyl)lysine (CML) were highest in the femurs and that they increased by the induction of diabetes. The administration of SCE also ameliorated the decreased femur strength and the accumulation of CML. Furthermore, when all of the carbohydrates in the chow of diabetic rats were replaced with free glucose, the administration of SCE significantly ameliorated a diabetes-induced increase in glycoalbumin and decrease in serum creatinine level and body weight. This study provides evidence to support that SCE ameliorates diabetes-induced abnormalities by improving the uptake of glucose by various organs.
Subject(s)
Blood Glucose/metabolism , Bone and Bones/drug effects , Glycation End Products, Advanced/metabolism , Plant Extracts/pharmacology , Salacia/chemistry , Administration, Oral , Animals , Body Weight , Chromatography, Liquid , Creatinine/blood , Diabetes Mellitus, Experimental/physiopathology , Glycoside Hydrolase Inhibitors/analysis , Glycoside Hydrolase Inhibitors/pharmacology , Male , Rats , Rats, Wistar , Serum Albumin/metabolism , Tandem Mass Spectrometry , Glycated Serum AlbuminABSTRACT
In the pathophysiology of diabetic retinopathy (DR), advanced glycation end products (AGEs) and vascular endothelial growth factor (VEGF) are thought to have important roles. It is known that VEGF causes a breakdown of the bloodretinal barrier (BRB) and retinal neovascularization; however, how AGEs affect the retina has largely remained elusive. OSSC1EK19 is a novel phytochemical component of Osteomeles schwerinae. The objective of the present study was to evaluate the protective effects of OSSC1EK19 on retinal vascular injury in AGEmodified rat serum albumin (AGE-RSA)-induced retinopathy. AGE-RSA-injected rat eyes were used investigate the protective effects of OSSC1EK19 on BRB breakdown. Intravitreal injection of OSSC1E-K19 prevented AGE-RSA-induced BRB breakdown and decreased retinal VEGF expression in retinal vessels. In addition, OSSC1E-K19 inhibited the loss of occludin, a significant tight junction protein. These results supported the potential therapeutic utility of OSSC1E-K19 for retinal vascular permeability diseases.
Subject(s)
Biphenyl Compounds/pharmacology , Diabetic Retinopathy/drug therapy , Glucosides/pharmacology , Plant Extracts/pharmacology , Retinal Vessels/pathology , Rosaceae/chemistry , Serum Albumin/physiology , Animals , Biphenyl Compounds/therapeutic use , Collagen/chemistry , Drug Evaluation, Preclinical , Glucosides/therapeutic use , Glycation End Products, Advanced/physiology , Male , Plant Extracts/therapeutic use , Rats, Sprague-Dawley , Retinal Vessels/drug effects , Tight Junctions/metabolism , Vascular Endothelial Growth Factor A/metabolism , Glycated Serum AlbuminABSTRACT
BACKGROUND: Diabetes mellitus is a common endocrine disorder characterized by hyperglycemia eventually resulting in long-term complications. Increased glycation of proteins is implicated in the pathogenesis of complications. For treatment of diabetes, Syzygium jambolanum and Cephalandra indica are frequently prescribed in homeopathy. However their role in glycation is not well elucidated. The present study aimed to evaluate the role of these homeopathic preparations in glycation induced structural modifications and further to examine their cellular protection ability. METHODS: In human erythrocytes, in vitro mother tincture and dilutions of S. jambolanum (Sj Ñ, 30c, 200c), C. indica (Ci Ñ, 30c, 200c) and standard antiglycator (AG) were compared and their antiglycation potential assessed by the estimating different markers of glycation (frcutosamines, carbonyls, bound sugar), structural modifications (free amino and thiol group). Phytochemical characterization (total phenolic, flavonoids and glycosides contents) was performed. RESULTS: The homeopathic preparations have different mode of action on albumin glycation modifications. Sj Ñ preparation demonstrated effective inhibition of all glycation, structural modifications except amino group protection. When dilutions were compared, Sj preparations showed reduction of glycation, structural modifications. All preparations showed significant erythrocyte protection. Sj Ñ preparation exhibited noteworthy antiglycation and cell protection ability as compared to AG. CONCLUSION: These homeopathic preparations especially Sj Ñ prevented glycation induced albumin modifications and subsequent toxicity in human eryrthrocytre in vitro. Further investigation of their potential as antiglycators is justified.
Subject(s)
Dipsacaceae , Homeopathy/methods , Plant Extracts/pharmacology , Protective Agents/pharmacology , Serum Albumin/antagonists & inhibitors , Syzygium , Erythrocytes/drug effects , Glycation End Products, Advanced , Humans , In Vitro Techniques , Plant Extracts/therapeutic use , Protective Agents/therapeutic use , Glycated Serum AlbuminABSTRACT
Postprandial hyperglycemia is a risk factor for cardiovascular disease and mortality. Serum 1,5-anhydroglucitol (1,5-AG) level is an useful clinical marker of glucose metabolism which reflects postprandial hyperglycemia more robustly compared to hemoglobin A1c (HbA1c). Relationship between serum 1,5-AG level and cardiovascular disease has been reported; however, comparison between HbA1c and 1,5-AG as markers of cardiovascular disease was not performed. We included 227 consecutive patients who underwent coronary angiography meeting the following inclusion criteria: (1) patients who had no history of coronary artery disease (CAD); (2) patients without acute coronary syndrome; (3) patients without poorly controlled diabetes mellitus; (4) patients without anemia, liver dysfunction, acute, and chronic renal failure and malnutrition; and (5) patients without adhibition of acarbose or Chinese herbal medicine. We measured HbA1c, glycoalbumin, and 1,5-AG. Serum 1,5-AG was significantly lower in patients with CAD (16.6 ± 8.50 vs. 21.1 ± 7.97 µg/ml, P < 0.001). Multivariable logistic regression analysis showed decrease in serum 1,5-AG was independently associated with the presence of denovo CAD (0.93, 95% CI 0.88-0.98, P = 0.006). Serum 1,5-AG was also independently associated with the presence of denovo CAD in patients without diabetes mellitus (0.94, 95% CI 0.88-0.99, P = 0.046). In conclusion, lower serum 1,5-AG was associated with the presence of denovo CAD. Serum 1,5-AG may identify high cardiovascular risk patients for denovo CAD in both diabetic and non-diabetic patients.
Subject(s)
Blood Glucose/metabolism , Coronary Artery Disease/blood , Deoxyglucose/blood , Diabetes Mellitus/blood , Glycated Hemoglobin/analysis , Hyperglycemia/blood , Aged , Biomarkers/blood , Coronary Angiography , Female , Glycation End Products, Advanced , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Prospective Studies , ROC Curve , Risk Factors , Serum Albumin , Glycated Serum AlbuminABSTRACT
OBJECTIVE: Postprandial hyperglycemia and blood glucose fluctuations increase the risk of macroangiopathy in patients with type 2 diabetes mellitus (T2DM). However, few studies have examined the effects of oral hypoglycemic drugs on blood glucose fluctuations in daily life. METHODS: Twenty-nine T2DM patients treated with acarbose were randomized to receive either sitagliptin (14 patients) or mitiglinide (15 patients) together with acarbose for 4 weeks. Patients were then switched to a combination of 10 mg mitiglinide and 0.2 mg voglibose for 4 weeks. All patients wore a continuous glucose monitoring (CGM) device for 5 - 7 days in week 3 of each treatment period. RESULTS: The percentage of blood glucose levels in the hyperglycemic range, blood glucose indices derived from 24-h CGM profiles and the glycemic parameters (HbA1c, glycated albumin and fasting plasma glucose) were significantly improved by adding sitagliptin or mitiglinide to ongoing acarbose therapy. These parameters also tended to improve in the mitiglinide/voglibose combination period. CONCLUSION: Daily blood glucose fluctuations were significantly improved by adding sitagliptin or mitiglinide to acarbose, and improved after switching to the mitiglinide/voglibose combination. Larger controlled studies are needed to verify the effects of adding sitagliptin or mitiglinide to acarbose on glucose fluctuations.
Subject(s)
Acarbose/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Isoindoles/therapeutic use , Pyrazines/therapeutic use , Triazoles/therapeutic use , Aged , Asian People , Blood Glucose/analysis , Drug Substitution , Drug Therapy, Combination , Female , Glycation End Products, Advanced , Humans , Hyperglycemia/drug therapy , Inositol/analogs & derivatives , Inositol/therapeutic use , Male , Middle Aged , Prospective Studies , Serum Albumin/analysis , Sitagliptin Phosphate , Glycated Serum AlbuminABSTRACT
Cyanidin and delphinidin are the main phenolic antioxidants in the grape (Vitis vinifera). The aim of this study was to investigate the in vitro and in vivo inhibitory effects of delphinidin and cyanidin chloride in the free and liposomal forms on the albumin glycation reaction. Delphinidin and cyanidin chlorides were encapsulated in the liposomes using an extrusion method. The rate of albumin glycation was evaluated using the ELISA method. Finally, in vivo anti-glycation of delphinidin and cyanidin chloride in the free and liposomal forms in diabetic mice was investigated. The encapsulation efficacies of delphinidin and cyanidin chloride in the liposomes were 89.05â% ± 0.18 and 85.00â% ± 0.15, respectively. In vitro treatment with 100 mg/mL delphinidin and cyanidin chloride in free forms could reduce the rate of albumin glycation to 30.50 ± 3.46 and 46.00 ± 2.50â%, respectively. Under identical conditions, the delphinidin and cyanidin chloride-loaded liposomes could reduce the rate of albumin glycation to 8.50 ± 2.10 and 14.60 ± 3.60â%, respectively. In vivo testing showed that anti-glycation activity of delphinidin and cyanidin in loaded forms was higher than in free forms. The daily administration of 100 mg/kg delphinidin chloride-loaded liposomes to diabetic mice at eight weeks could decrease the rate of albumin and HbA1c glycation to 46.35 ± 1.20 and 3.60 ± 0.25â%, respectively. Moreover, under identical conditions, the loaded liposomes with cyanidin chloride could decrease the rate of albumin and HbA1c glycation to 55.56 ± 1.32 and 4.95 ± 0.20â%, respectively. The findings showed that delphinidin and cyanidin chloride, in particular in the liposomal forms, could be used for treatment of diabetes mellitus complications.
Subject(s)
Anthocyanins/therapeutic use , Antioxidants/therapeutic use , Diabetes Mellitus/drug therapy , Hypoglycemic Agents/therapeutic use , Phytotherapy , Plant Extracts/therapeutic use , Vitis/chemistry , Animals , Anthocyanins/administration & dosage , Anthocyanins/pharmacology , Antioxidants/administration & dosage , Antioxidants/pharmacology , Diabetes Mellitus/metabolism , Disease Models, Animal , Glycated Hemoglobin/metabolism , Glycation End Products, Advanced , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacology , Liposomes , Male , Mice , Mice, Inbred BALB C , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Serum Albumin/metabolism , Glycated Serum AlbuminABSTRACT
AIMS: HbA(1c) values are unreliable in patients with diabetes who have chronic kidney disease who receive iron and/or erythropoiesis stimulating agents. The study aimed to evaluate the utility of the complementary glycaemic markers glycated albumin, fructosamine and 1,5 anhydroglucitol in this group of patients. METHODS: A prospective study of patients with Type 2 diabetes and chronic kidney disease stage IIIB/IV undergoing intravenous iron or erythropoiesis-stimulating agent therapy. Glycaemic control was monitored using HbA(1c), seven-point daily glucose thrice weekly, continuous glucose monitoring, glycated albumin, fructosamine and 1,5 anhydroglucitol. RESULTS: Fifteen patients [9 men; median age 72 years (interquartile range 68-74), follow-up period (16.4 ± 3.7 weeks)] received parenteral iron; 15 patients [11 men; 70 years (interquartile range 62-75), (17.3 ± 3.3 weeks)] received erythropoiesis-stimulating agent. HbA(1c) fell following treatment with both iron [57 mmol/mol (7.4%) to 53 mmol/mol (7.0%), P < 0.001] and erythropoiesis-stimulating agent [56 mmol/mol (7.3%) to 49 mmol/mol (6.6%), P = 0.01] despite mean blood glucose remaining unchanged (iron: 9.55 to 9.71 mmol/l, P = 0.07; erythropoiesis-stimulating agent: 8.72 to 8.78 mmol/l, P = 0.89). Unlike HbA1c , the glycated albumin, fructosamine and 1,5 anhydroglucitol levels did not change following iron [glycated albumin (16.8 to 16.3%, P = 0.10); fructosamine (259.5 to 256 µmol/l, P = 0.89); 1,5 anhydroglucitol (54.2 to 50.9 µmol/l, P = 0.89)] or erythropoiesis-stimulating agent [glycated albumin (17.9 to 17.5%, P = 0.29), fructosamine (324.3 to 306.0 µmol/l, P = 0.52), 1,5 anhydroglucitol (58.2 to 46.7 µmol/l, P = 0.35)]. Despite this, HbA(1c) was consistently the marker most closely related to mean blood glucose before and after each treatment (R range 0.7-0.88). CONCLUSIONS: These data indicate that HbA(1c) was statistically most closely related to mean blood glucose, but clinical trends in glycaemia in patients undergoing iron or erythropoiesis-stimulating agent therapy are likely best assessed by including one of these additional glycaemic markers.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diabetic Nephropathies/drug therapy , Erythropoietin/therapeutic use , Glycated Hemoglobin/drug effects , Glycated Hemoglobin/metabolism , Hematinics/therapeutic use , Iron/therapeutic use , Renal Insufficiency, Chronic/drug therapy , Administration, Intravenous , Aged , Biomarkers/blood , Blood Glucose/metabolism , Delivery of Health Care , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/physiopathology , Diabetic Nephropathies/blood , Diabetic Nephropathies/physiopathology , Epoetin Alfa , Female , Follow-Up Studies , Fructosamine/blood , Glycation End Products, Advanced , Humans , Male , Monitoring, Physiologic , Prospective Studies , Recombinant Proteins/therapeutic use , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/physiopathology , Serum Albumin/metabolism , Severity of Illness Index , Time Factors , Treatment Outcome , Glycated Serum AlbuminABSTRACT
In this study, the in vivo effect of the crude extract and n-butanol and aqueous residual fractions of Baccharis articulata (Lam.) Pers. on serum glucose levels, insulin secretion and liver and muscle glycogen content, as well as in vitro action on serum intestinal disaccharidase activity and albumin glycation were investigated. Oral administration of the extract and fractions reduced glycemia in hyperglycemic rats. Additionally, the n-butanol fraction, which has high flavonoids content, stimulated insulin secretion, exhibiting an insulinogenic index similar to that of glipizide. Also, the n-butanol fraction treatment significantly increased glycogen content in both liver and muscle tissue. In vitro incubation with the crude extract and n-butanol and aqueous residual fractions inhibited maltase activity and the formation of advanced glycation end-products (AGEs). Thus, the results demonstrated that B. articulata exhibits a significant antihyperglycemic and insulin-secretagogue role. These effects on the regulation of glucose homeostasis observed for B. articulata indicate potential anti-diabetic properties.
Subject(s)
Baccharis/chemistry , Glucose/metabolism , Hypoglycemic Agents/pharmacology , Plant Extracts/pharmacology , 1-Butanol/chemistry , Animals , Blood Glucose/drug effects , Diabetes Mellitus, Experimental/metabolism , Flavonoids/chemistry , Glucose Tolerance Test , Glycation End Products, Advanced , Glycogen/metabolism , Glycoside Hydrolase Inhibitors , Glycosylation/drug effects , Homeostasis/drug effects , Hypoglycemic Agents/chemistry , Insulin/blood , Insulin/metabolism , Insulin Secretion , Male , Phenols/chemistry , Plant Extracts/chemistry , Rats , Rats, Wistar , Serum Albumin , Time , Time Factors , Glycated Serum AlbuminABSTRACT
To determine whether miglitol administration improves glycemic control and reduces the frequency of hypoglycemia in type 1 diabetes mellitus (T1DM) patients treated with intensive insulin therapy, we analyzed the effect of miglitol on daily insulin doses, body weight, hypoglycemia, and incretin hormone responses during meal tolerance tests (MTT). Eleven T1DM subjects (21-77 years) undergoing intensive insulin therapy, took 25 mg (weeks 0-4) and 50 mg miglitol (weeks 4-12) thrice daily, immediately before meals. At weeks 0 and 12, 9 of 11 subjects underwent MTT. In present study, mean HbA1c, glycoalbumin, and 1,5-anhydroglucitol levels were significantly improved. The blood glucose level 1 h after dinner was significantly lower at week 12 than at week 0 (p = 0.008). From week 0 to 12, there was a significant decrease in the body mass index (BMI; p = 0.0051), frequency of preprandial hypoglycemic events (p = 0.012), and daily bolus insulin dosage (p = 0.018). The change in active glucagon-like peptide-1 (GLP-1) at 120 min significantly increased at week 12 (p = 0.015). The change in total glucose-dependent insulinotropic peptide (GIP) significantly decreased in the MTT at week 12. These results demonstrate that addition of miglitol on intensive insulin therapy in T1DM patients has beneficial effects on reducing BMI, bolus and total insulin dosage, and frequency of preprandial hypoglycemic events. MTT findings suggest that this combination therapy improves blood glucose control by delaying carbohydrate absorption and modifying the responses of incretins, GIP, and GLP-1.
Subject(s)
1-Deoxynojirimycin/analogs & derivatives , Diabetes Mellitus, Type 1/drug therapy , Hyperglycemia/prevention & control , Hypoglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Incretins/blood , Insulin/administration & dosage , 1-Deoxynojirimycin/administration & dosage , 1-Deoxynojirimycin/adverse effects , 1-Deoxynojirimycin/therapeutic use , Adult , Aged , Deoxyglucose/blood , Diabetes Mellitus, Type 1/blood , Drug Therapy, Combination/adverse effects , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/adverse effects , Enzyme Inhibitors/therapeutic use , Gastric Inhibitory Polypeptide/blood , Glucagon-Like Peptide 1/blood , Glycated Hemoglobin/analysis , Glycation End Products, Advanced , Glycoside Hydrolase Inhibitors , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Insulin/adverse effects , Insulin/therapeutic use , Male , Middle Aged , Serum Albumin/analysis , Weight Loss/drug effects , Young Adult , Glycated Serum AlbuminABSTRACT
OBJECTIVE: Compared to vegetable oils in their unmodified state, partially-hydrogenated fat is associated with less favorable effects on cardiovascular disease (CVD) risk factors. Acceptable alternatives must be adjudicated. Our objective was to assess the effect of a recent commercial fat substitution, corn oil for partially-hydrogenated soybean oil. METHODS: Using a double-blind cross-over design, 30 postmenopausal women >or=50 years with LDL-cholesterol concentrations >or=120 mg/dL were randomly assigned to each of two 35-day phases; all food and beverage was provided to maintain body weight. Corn or partially-hydrogenated soybean oil was incorporated throughout the diet and contributed two-thirds of fat. Primary outcomes included fasting and non-fasting lipid, lipoprotein, apolipoprotein, and fasting high sensitivity C-reactive protein (hsCRP) concentrations; secondary outcomes included fasting small dense LDL (sdLDL)-cholesterol, remnant lipoprotein cholesterol (RemLC), glycated albumin, adiponectin and immunoreactive insulin concentrations, and endogenous cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) activities. RESULTS: Relative to the partially-hydrogenated soybean oil enriched diet, the corn oil enriched diet resulted in lower fasting total cholesterol (7%; P<0.0001), LDL-cholesterol (10%; P<0.0001), VLDL-cholesterol (7%; P=0.052), apo B (9%; P<0.0001), lipoprotein (a) [Lp(a)] (5%; P=0.024), sdLDL-cholesterol (17%; P=0.001), and RemLC (20%; P=0.007) concentrations, and no significant effect on the other outcomes. Changes in postprandial (4-h post-meal) lipid, lipoprotein and apolipoprotein concentrations were similar to the fasting state. CONCLUSION: The replacement of partially-hydrogenated soybean oil with corn oil favorably affects a range of CVD risk factors and is an appropriate option to decrease cardiovascular disease risk factors in moderately hypercholesterolemic individuals.
Subject(s)
Cardiovascular Diseases/prevention & control , Corn Oil/administration & dosage , Hypercholesterolemia/diet therapy , Postmenopause , Soybean Oil/administration & dosage , Adiponectin/blood , Aged , Apolipoprotein A-I/blood , Apolipoproteins B/blood , Biomarkers/blood , C-Reactive Protein/metabolism , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Cholesterol Ester Transfer Proteins/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cholesterol, VLDL/blood , Corn Oil/adverse effects , Cross-Over Studies , Double-Blind Method , Fasting/blood , Female , Glycation End Products, Advanced , Humans , Hydrogenation , Hypercholesterolemia/blood , Hypercholesterolemia/complications , Insulin/blood , Middle Aged , Serum Albumin/metabolism , Severity of Illness Index , Soybean Oil/adverse effects , Sterol O-Acyltransferase/blood , Time Factors , Treatment Outcome , Triglycerides/blood , Glycated Serum AlbuminABSTRACT
OBJECTIVE: A1C levels have been shown to be elevated in relation to glycemia in late pregnancy, although the precise mechanisms remain undetermined. We hypothesized that iron deficiency is involved in the A1C increase in late pregnancy. RESEARCH DESIGN AND METHODS: In study 1, A1C, serum glycated albumin, erythrocyte indexes, and iron metabolism indexes were determined in 47 nondiabetic pregnant women not receiving iron supplementation who were divided into four groups according to gestational period (group I, 21-24 weeks; group II, 25-28 weeks; group III, 29-32 weeks; and group IV, 33-36 weeks). In study 2, these determinants were obtained at two gestational periods (20-23 weeks and 32-33 weeks) in 17 nondiabetic pregnant women. RESULTS: In study 1, A1C levels were higher in groups III and IV than those in groups I and II, whereas serum glycated albumin levels were not different among these four groups. Hemoglobin, mean corpuscular hemoglobin (MCH), serum transferrin saturation, and serum ferritin were lower in groups III and IV. A1C levels were negatively correlated with MCH, serum transferrin saturation, and serum ferritin. In study 2, A1C levels were significantly increased at gestational weeks 32-33 from those at weeks 20-23, whereas serum glycated albumin levels did not differ between the two gestational periods. MCH, serum transferrin saturation, and serum ferritin were decreased at gestational weeks 32-33. A1C levels showed a negative correlation with MCH, serum transferrin saturation, and serum ferritin. CONCLUSIONS: A1C levels were elevated in late pregnancy owing to iron deficiency. Serum glycated albumin may offer a better index for monitoring glycemic control in pregnancy.
Subject(s)
Anemia, Iron-Deficiency/blood , Glycated Hemoglobin/metabolism , Pregnancy Complications/blood , Serum Albumin/metabolism , Adult , Diabetes, Gestational/blood , Erythrocytes/metabolism , Female , Glycation End Products, Advanced , Humans , Longitudinal Studies , Pregnancy , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Reference Values , Glycated Serum AlbuminABSTRACT
Despite the high levels of polyphenolic phytochemicals in grain sorghum and its position as a major food staple, there has been a lack of research on its effects on both animal and human health and disease prevention. These phenolic compounds, mainly located in the bran fraction, result in the plant having substantial antioxidant properties. This study examined the effect of ethanol extracts of several varieties of sorghum (S. bicolor) bran on albumin glycation, a non-enzymatic process thought to be important in the pathogenesis of many diabetic complications. Sorghum brans with a high phenolic content and high antioxidant properties inhibited protein glycation, whereas sorghum brans that are low in these properties did not inhibit this process. Ethanol extracts of wheat, rice or oat bran did not inhibit protein glycation. Although one high phenolic sorghum bran variety (sumac) inhibited protein glycation by approximately 60%, it produced only a 20% decrease in methylglyoxal mediated albumin glycation. These results suggest that certain varieties of sorghum bran may affect critical biological processes that are important in diabetes and insulin resistance. These results distinguish select sorghum brans from the common food brans and suggest a nutraceutical rationale for its human consumption.
Subject(s)
Dietary Supplements , Glycosylation , Plant Extracts/chemistry , Serum Albumin, Bovine/chemistry , Serum Albumin/chemistry , Sorghum/chemistry , Animals , Antioxidants/chemistry , Cattle , Dietary Fiber , Glycation End Products, Advanced , In Vitro Techniques , Phenols/chemistry , Glycated Serum AlbuminABSTRACT
Intensive insulin therapy composed of bolus and basal insulin has been believed as the most powerful recipe for glycemic control of both type 1 and type 2 diabetes. In this study, we investigated the effects of changes in basal/total daily insulin ratio (B/TD ratio) in type 2 diabetes patients on intensive insulin therapy including insulin glargine. The B/TD ratio used in our Japanese patients was about 0.35, and the ratio was increased up to about 0.46+/-0.12 without change of total insulin daily dose. After 24-week-treatment, mean glycated albumin of the patients whose B/TD ratio was increased was significantly lower than those of the patients whose B/TD ratio was not changed. Our results suggest that adequate supplementation of basal insulin may be important for maximum effect of bolus insulin even in Japanese who have serious defect in postprandial rapid insulin secretion.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Insulin/analogs & derivatives , Insulin/therapeutic use , Dose-Response Relationship, Drug , Glycation End Products, Advanced , Glycosylation , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Insulin/administration & dosage , Insulin Glargine , Insulin, Isophane/therapeutic use , Insulin, Long-Acting , Serum Albumin/metabolism , Glycated Serum AlbuminABSTRACT
We have shown previously that Japanese radish (Raphanus sativus) sprouts (JRS) improve blood glucose levels in diabetic rats. In this study, we investigated the components in JRS that caused this hypoglycemic effect, by examining the effects of water-soluble (WSE) and fat-soluble (FSE) extracts of JRS on diabetes markers in normal (NM) and streptozotocin (STZ)-induced diabetic (DM) rats. The NM and DM rats were divided into a control group and 2 test groups (WSE (2.2%) or FSE (0.2%)), with the rats (n = 6/group) then being maintained for 3 wk on either a control diet or one of the test diets; this was followed by the measurement of serum concentrations of glucose, insulin, glycoalbumin, fructosamine, ketone bodies, and lipids (cholesterol and triglyceride) and liver concentrations of lipids (total lipid, total cholesterol, and triglyceride). The FSE suppressed insulin secretion and improved lipid metabolism in the NM rats. The effect of WSE was different from that of the FSE as it decreased blood glucose levels without increasing insulin secretion and also lowered glycoalbumin and fructosamine levels in the DM rats. Therefore, the WSE have potential as functional food components with the hypoglycemic effect.
Subject(s)
Carbohydrate Metabolism/drug effects , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/pharmacology , Lipid Metabolism/drug effects , Plant Extracts/pharmacology , Raphanus , Animals , Biomarkers/blood , Biomarkers/metabolism , Blood Glucose/drug effects , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Diet/methods , Fructosamine/blood , Glycation End Products, Advanced , Insulin/blood , Ketone Bodies/blood , Lipids/blood , Liver/drug effects , Liver/metabolism , Male , Phytotherapy/methods , Raphanus/chemistry , Rats , Rats, Wistar , Seedlings , Serum Albumin/drug effects , Streptozocin , Time Factors , Glycated Serum AlbuminABSTRACT
Calcium binding to glycated, penicilloylated, acetylated, and normal defatted human serum albumin as well as to mercapt- and nonmercaptalbumin was studied by equilibrium dialysis of radioactive Ca2+. Binding was quantified by five Scatchard constants [ni = 1, (i = 1-4) and n5 = 10]. Glycation resulted in increased k1- and k2-values and unchanged k3-k5-values, whereas penicilloylation increased all five association constants. The increments were greater the more pronounced the modification, and the enhancements caused by penicilloylation were, for the same degree of modification, greater than those produced by glycation. In contrast, acetylation by acetylsalicylate did not affect calcium binding. Likewise, binding to mercapt- and nonmercaptalbumin was the same, a finding showing that the thiol group of cysteine 34 is not important for calcium binding. D-Glucose and penicillin G are known to react with lysine residues of albumin, and the enhancement of binding resulting from glycation or penicilloylation is probably brought about by unspecific electrostatic effects, possibly supplemented by conformational changes of the protein molecule. The relative importance of the three domains of human serum albumin for calcium binding is discussed.
Subject(s)
Calcium/metabolism , Serum Albumin/chemistry , Serum Albumin/metabolism , Acetylation , Binding Sites , Cations, Divalent , Dialysis , Glycation End Products, Advanced , Humans , Penicillin G/chemistry , Structure-Activity Relationship , Glycated Serum AlbuminABSTRACT
OBJECTIVE: To evaluate the effect of vitamin E supplementation on the susceptibility of low-density lipoprotein (LDL) and LDL subfractions to oxidation and on protein glycation in non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Twenty-one men with NIDDM (HbA1c = 6-10%), ages 50-70, were randomly assigned to either 1,600 IU/day of vitamin E or placebo for 10 weeks after a 4-week placebo period. LDL and LDL subfractions were isolated after 4 weeks of placebo and after 6 and 10 weeks of therapy. Susceptibility of LDL to copper-mediated oxidation was measured by conjugated diene formation (lag time) and formation of thiobarbituric acid-reactive substances (TBARS). Fasting serum glucose, mean weekly blood glucose, HbA1c, and glycated plasma protein concentrations were also determined at these time points. RESULTS: Vitamin E content in plasma and LDL increased 4.0- and 3.7-fold, respectively, in the vitamin E-treated group. Vitamin E decreased the susceptibility of LDL to oxidation in comparison with placebo (lag time, 243 +/- 46 vs. 151 +/- 22 min, P < 0.01; 3 h TBARS, 24 +/- 12 vs. 66 +/- 18 nmol malondialdehyde/mg LDL, P < 0.05). Vitamin E content also increased significantly in both buoyant and dense LDL subfractions, and their oxidation was dramatically reduced. The lag time of LDL oxidation correlated well with the content of vitamin E in both LDL and its subfractions (r = 0.69-0.92). Glycemic indexes did not change significantly in either group during the study. Protein glycation, including glycated hemoglobin, glycated albumin, glycated total plasma proteins, and glycated LDL were unchanged in the vitamin E group. CONCLUSIONS: Supplementation of vitamin E in NIDDM leads to enrichment of LDL and LDL subfractions and reduced susceptibility to oxidation. Despite a greater percentage increase in vitamin E content in small dense LDL, it remained substantially more susceptible to oxidation than was buoyant LDL. This suggests that dense, LDL may gain less protection against oxidation from antioxidant supplementation than does larger, more buoyant LDL. In contrast to previous reports, vitamin E supplementation did not reduce glycation of intracellular or plasma proteins.
Subject(s)
Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Glycoproteins , Lipoproteins, LDL/blood , Vitamin E/therapeutic use , Aged , Blood Glucose/metabolism , Blood Proteins/analysis , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Copper , Fructosamine , Glycated Hemoglobin/analysis , Glycation End Products, Advanced , Glycosylation , Hexosamines/analysis , Homeostasis , Humans , Insulin/blood , Lipoproteins, LDL/drug effects , Male , Middle Aged , Oxidation-Reduction , Serum Albumin/analysis , Thiobarbituric Acid Reactive Substances , Time Factors , Triglycerides/blood , Vitamin E/blood , Glycated Serum Proteins , Glycated Serum AlbuminABSTRACT
Oxidative stress and protein glycation are closely related processes that may contribute to the development of complications in diabetes mellitus. Treatment with antioxidants could protect against these processes at a biochemical level, and we have therefore investigated the effects of ascorbate and desferrioxamine treatment in the streptozotocin diabetic rat. Diabetic animals were given ascorbate 1 g/l in drinking water or desferrioxamine 6 mg/kg/day by subcutaneous injection and were killed after 6 weeks. In diabetic animals, oxidative stress was increased as shown by increased levels of conjugated dienes (CD) in plasma and malondialdehyde (MDA) in plasma, erythrocyte membranes, and urine. In addition, there was depletion of the nutritional antioxidants ascorbate, alpha-tocopherol, and retinol. Insulin treatment returned all of these parameters to normal. Ascorbate supplementation or desferrioxamine treatment alone failed to reduce oxidative stress, but a combination of both interventions restored MDA, CD, and antioxidant vitamins to control values. Both ascorbate and desferrioxamine also reduced HbA1c and glycated albumin levels. Treatment with antioxidants can reduce both oxidative stress and protein glycation and may help to reduce the risk of developing diabetic complications. However, ascorbate can have both prooxidant and antioxidant effects in vivo, and its use in pharmacological doses should be approached with caution.