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PubMed2004

Hypoglycemic activity of inorganic constituents in Eugenia jambolana seed on streptozotocin-induced diabetes in rats.

Medicinal herbs used in indigenous medicines for the management of diabetes mellitus contain both organic and inorganic constituents. Some of these inorganic trace elements possess antidiabetic properties, which accounts for the activity of medicinal herbs. The aim of this study was to analyze the inorganic trace elements present in Eugenia jambolana seeds and to evaluate the hypoglycemic activity of the inorganic part of E. jambolana seeds on streptozotocin-induced diabetes. The seeds of E. jambolana seeds were reduced to ash and the inorganic elements present were assayed. The hypoglycemic efficacy of the inorganic part was tested by the glucose tolerance test on streptozotocin-induced diabetes. Elements such as zinc, chromium, vanadium, potassium, and sodium, possessing hypoglycemic activity, were present in the seed. The E. jambolana seed ash-treated diabetic rats exhibited normoglycemia and better glucose tolerance. The conclusion that the inorganic constituents might play a important role in the antidiabetic nature E. jambolana seeds was reached.

Animals↗
PubMed2005

Hypoglycemic activity of polysaccharide fractions containing beta-glucans from extracts of Rhynchelytrum repens (Willd.) C.E. Hubb., Poaceae.

Beta-glucans are soluble fibers with physiological functions, such as interference with absorption of sugars and reduction of serum lipid levels. The objective of the present study was to analyze the distribution of beta-glucans in different tissues of the African grass species Rhynchelytrum repens and also to evaluate their hypoglycemic activity. Leaf blades, sheaths, stems, and young leaves of R. repens were submitted to extraction with 4 M KOH. Analysis of the fractions revealed the presence of arabinose, glucose, xylose, and traces of rhamnose and galactose. The presence of beta-glucan in these fractions was confirmed by hydrolyzing the polymers with endo-beta-glucanase from Bacillus subtilis, followed by HPLC analysis of the characteristic oligosaccharides produced. The 4 M KOH fractions from different tissues were subjected to gel permeation chromatography on Sepharose 4B, with separation of polysaccharides with different degrees of polymerization, the highest molecular mass (above 2000 kDa) being found in young leaves. The molecular mass of the leaf blade polymers was similar (250 kDa) to that of maize coleoptile beta-glucan used for comparison. The 4 M KOH fraction injected into rats with streptozotocin-induced diabetes showed hypoglycemic activity, reducing blood sugar to normal levels for approximately 24 h. This performance was better than that obtained with pure beta-glucan from barley, which decreased blood sugar levels for about 4 h. These results suggest that the activity of beta-glucans from R. repens is responsible for the use of this plant extract as a hypoglycemic drug in folk medicine.

Animals↗
PubMed1983

Ciglitazone, a new hypoglycemic agent. I. Studies in ob/ob and db/db mice, diabetic Chinese hamsters, and normal and streptozotocin-diabetic rats.

Ciglitazone, 5-[4-(1-methylcyclohexylmethoxy) benzyl]-thiazolidine-2,4-dione, is a new hypoglycemic agent orally active in the obese-hyperglycemic animal models. In C57BL/6J-ob/ob mice, treatment with 100 mg/kg ciglitazone for 2 days elicited a drastic fall in blood glucose. It also decreased plasma insulin, triglycerides, and free fatty acids and food intake without affecting the body weight. Its hypoglycemic activity was independent of its effect on food intake. Regranulation of islet beta-cells and increased pancreatic insulin content were observed in ob/ob mice treated for 41-44 days with 100 mg/kg/day ciglitazone. Ciglitazone showed no effect on food intake, blood glucose, or pancreatic islet beta-cells in a group of lean C57BL/6J-+/? mice concomitantly treated at a dose of 150 mg/kg/day. In C57BL/KsJ-db/db mice, ciglitazone decreased blood glucose and food intake. The untreated db/db mice lost weight despite hyperphagia, whereas the ciglitazone-treated db/db mice gained weight. In the spontaneously diabetic Chinese hamsters, ciglitazone showed no significant effect on food intake, body weight, blood glucose, or insulin content in either plasma or pancreas, but it lowered plasma lipids. In normal rats, ciglitazone failed to affect fasting blood glucose but improved glucose tolerance without increasing insulin secretory response to glucose. In streptozotocin-diabetic rats, it showed no effect on blood glucose or glycemic response to exogenous insulin. The hypoglycemic activity of ciglitazone was specific for obese-hyperglycemic and insulin-resistant animals.

Animals↗
PubMed1987

Studies of midaglizole (DG-5128). A new type of oral hypoglycemic drug in healthy subjects.

Midaglizole (DG-5128), 2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenylethyl]pyridine dihydrochloride sesquihydrate, is a novel alpha 2-adrenoceptor antagonist. Its effects on plasma glucose, immunoreactive insulin (IRI), and immunoreactive glucagon (IRG) in healthy male volunteers were investigated. Volunteers received single oral administrations of midaglizole (150-500 mg), multiple increasing oral administration on 3 separate days (150-300 mg 3 times daily), or successive daily oral administration for 1 wk (200 mg 3 times daily). The hypoglycemic action of midaglizole was observed within 0.5-1.0 h after its administration and thereafter for 5 h. The maximum hypoglycemic effect was found 1.0-1.5 h after administration. Midaglizole decreased postprandial hyperglycemia in a dose-dependent manner. In the fasting state, midaglizole significantly increased IRI secretion and suppressed IRG secretion. Midaglizole inhibited epinephrine-induced platelet aggregation after successive administration for 1 wk (200 mg 3 times daily). The plasma half-life of midaglizole was only 3 h, and the drug was rapidly excreted into the urine and feces, with greater than 80% in its unchanged form, within 24 h. Midaglizole did not affect the results of any clinical or laboratory tests performed. Our data indicate that midaglizole is a possible hypoglycemic agent. Further clinical investigations are required to confirm its effects on diabetes mellitus.

Administration, Oral↗
PubMed1997

Glipizide-GITS does not increase the hypoglycemic effect of mild exercise during fasting in NIDDM.

OBJECTIVE: This study compared the effect of mild exercise while fasting on plasma glucose concentrations in subjects with NIDDM treated with extended-release glipizide and subjects not taking an oral hypoglycemic agent. RESEARCH DESIGN AND METHODS: Twenty-five moderately obese subjects with NIDDM were randomized to treatment with extended-release glipizide or placebo. After 9 weeks of treatment, they fasted overnight, took their study drug, omitted breakfast, and exercised on a treadmill for 90 min. Glucose, insulin, and C-peptide concentrations were measured before, during, and after exercise. RESULTS: On the fasting-exercise day, fasting glucose concentrations were lower (153 vs. 241 mg/dl, P < 0.01) and insulin and C-peptide concentrations higher in the extended-release glipizide group. The decrement of glucose from the fasting baseline was modest and equivalent in the two groups: 17 vs. 21 mg/dl at the end of exercise and 28 vs. 27 mg/dl after 2 h of recovery. No subject had hypoglycemic symptoms. CONCLUSIONS: Chronic use of extended-release glipizide does not enhance the hypoglycemic effect of fasting plus mild exercise for people with NIDDM. Routine lifestyle treatments for NIDDM may be continued during ongoing use of this agent.

Adult↗
PubMed1976

Species-specific hypoglycemic activity of triphenylphosphoranylideneacetophenones.

The species-specific hypoglycemic activity of two 2-triphenylphosphoranylideneacetophenones is described. 2-Triphenylphosphoranylideneacetophenone (SK&F 45359) and 2-triphenylphosphoranylidene-m-trifluoromethyl-acetophenone (SK&F 62775) were hypoglycemic in various rat models, but failed to exhibit hypoglycemic activity in other species.

Acetophenones↗
PubMed2006

Hypoglycemic effects of vanadium on alloxan monohydrate induced diabetic dogs.

The hypoglycemic effects after oral administration of vanadium have been studied previously in many species such as rats, mice and even humans. However, there has been no prior report on the glucose lowering effect of vanadium on diabetic dogs. Therefore, the purpose of this study was to evaluate the hypoglycemic effects of oral vanadium on diabetic dogs. Diabetes mellitus in the dogs studied was induced by alloxan monohydrate intravenous injection. The dogs were divided into two groups, one was the diabetic control (DC) group (n = 4) and the other was the vanadium treated (DV) group (n = 6). Fresh water was supplied to the dogs in the DC group, but sodium metavanadate solution (0.1approximately 0.2 mg/ml) was given to the dogs in DV group from one week after the alloxan injection. The fasting glucose levels, fructosamine and serum chemistry profiles were compared between the two groups weekly for three weeks. The fasting blood glucose levels in DV group were significantly lower than those in the DC group (p < 0.01). Fructosamine levels in the DV group were also lower than those in the DC group (p < 0.05). The serum chemistry profiles were not significantly different in comparisons between the two groups. However, the cholesterol levels were significantly lower in the DV group compared to the DC group (p < 0.05). Our findings showed that oral vanadium administration had a hypoglycemic effect on chemically induced diabetic dogs.

Alanine Transaminase↗
PubMed1991

A new generation of oral hypoglycemics. Their use, measurement, and effects on insurance risk assessment.

The increased use of oral hypoglycemics among the more than 14 million diabetics in the United States and the development of new pharmaceutical formulations requires the continued surveillance of their use in the insurance applicant population. Routine monitoring of urine glucose or even blood glucose or fructosamine measurements often fail to detect the diabetic using oral hypoglycemics. Urine analysis for the use of first generation sulfonylureas has shown a declining prevalence of their use due to the increased number of prescriptions written for newer and more effective drugs. In order to monitor the use of these second-generation oral hypoglycemics, an immunoassay was developed to detect the use of glyburide, 1-[4-[2-(5 chloro-2-methoxybenzamido) ethyl]-phenyl] sulfonyl]-3-cyclohexylurea. After testing in a defined population of known users of this class of sulfonylureas, the assay was applied to a random population of 12,000 applicants applying for life insurance. Results demonstrate the predictive value of this assay in determining the prevalence of use of this drug in the insurance-buying population and its assistance in risk assessment.

Diabetes Mellitus↗
PubMed2000

Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root.

Hypoglycemic, diuretic and hypocholesterolemic effects of roots of W. somnifera (ashvagandha) were assessed on human subjects. Six mild NIDDM subjects and six mild hypercholesterolemic subjects were treated with the powder of roots of W. somnifera for 30 days. Suitable parameters were studied in the blood and urine samples of the subjects along with dietary pattern before and at the end of treatment period. Decrease in blood glucose was comparable to that of an oral hypoglycemic drug. Significant increase in urine sodium, urine volume, significant decrease in serum cholesterol, triglycerides, LDL (low density lipoproteins) and VLDL (very low density lipoproteins) cholesterol were observed indicating that root of W. somnifera is a potential source of hypoglycemic, diuretic and hypocholesterolemic agents. Clinical observations revealed no adverse effects.

Adult↗
PubMed2003

Hypoglycemic mechanism of ginseng glycopeptide.

AIM: To study the hypoglycemic mechanism of ginseng glycopeptide (GGP). METHODS: After administration of GGP, the levels of insulin, lactate dehydrogenase (LDH), lactic acid (LC), and oxygen consumption, as well as blood glucose (BG) and liver glycogen (LG) were measured. Based on these measurement results, the effects of GGP on insulin secretion and anaerobic/aerobic glycolysis were evaluated. Adenylate cyclase (AC) activity and cAMP level were measured to study the effects of GGP on BG and LG metabolism and to determine whether the effects were through second transmitting message system. Propranolol (beta-receptor antagonist) and phentolamine (alpha-receptor antagonist) were used to investigate whether hypoglycemic activity of GGP was through beta- or alpha-adrenoceptor. [3H]DHA (antagonist of beta-adrenoceptor) was used to determine GGP binding affinity to beta-adrenoceptor. Citrate synthetase (CTS), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and cytochrome oxidase (CCO) activities were measured to explore GGP effects on aerobic glycolysis in liver mitochondria. Phosphorylase (PP) activity was measured to study GGP effects on liver glycogen metabolism. RESULTS: cAMP content and AC activity were increased when BG and LG contents in liver of mice decreased. The decrease in liver glycogen induced by GGP was inhibited by pretreatment with propranolol. Radioligand receptor assay showed that GGP was competing in vitro with [3H]DHA to bind to beta-adrenoceptor of duck erythrocyte membrane, and IC50 of GGP was 63 nmol/L. GGP inhibited LDH activity at an appropriate dosage, at which contents of BG and LG could be effectively lowered. GGP also stimulated activities of SDH, MDH, CCO, CTS, and PP. CONCLUSION: The hypoglycemic activity of GGP may be attributed to the enhancement of aerobic glycolysis through stimulation of beta-adrenoceptor and increase of various rate-limiting enzyme activities related to tricarboxylic acid cycle.

Adrenergic beta-Agonists↗
PubMed2002

Mechanism of action of a hypoglycemic principle isolated from fenugreek seeds.

Mechanism of action of an orally active hypoglycemic principle isolated from water extract of seeds of Trigonella foenum graecum (fenugreek) was investigated in alloxan induced subdiabetic and overtly diabetic rabbits of different severities. The active principle was orally administered to the subdiabetic and mild diabetic rabbits (five in each group) at a dose of 50 mg/kg body weight for 15 days. The treatment produced significant attenuation of the glucose tolerance curve and improvement in the glucose induced insulin response, suggesting that the hypoglycemic effect may be mediated through stimulating insulin synthesis and/or secretion from the beta pancreatic cells of Langerhans. Prolonged administration of the same dose of the active principle for 30 days to the severely diabetic rabbits (n = 5) lowered fasting blood glucose significantly, but could elevate the fasting serum insulin level to a much lower extent, which suggests an extra-pancreatic mode of action for the active principle. The effect may also be by increasing the sensitivity of tissues to available insulin. The hypoglycemic effect was observed to be slow but sustained, without any risk of developing severe hypoglycemia.

Animals↗
PubMed2003

[Hypoglycemic effect of polysaccharide-coated insulin liposomes after oral administration in mice].

AIM: To evaluate the hypoglycemic effect of chitosan-coated and sodium alginate-coated insulin liposomes after oral administration in mice. METHODS: Insulin-liposomes were prepared by reverse-phase evaporation. Chitosan and alginate coating was carried out by mixing liposomal suspension with chitosan and sodium alginate solutions, followed by incubation. The particle size and morphology of insulin-liposomes were determined using laser light scattering instrument and transmission electron microscopy (TEM). The entrapment efficiency was analyzed using HPLC and ultracentrifuge. The protection of insulin from peptic and tryptic digestion was studied with HPLC. The hypoglycemic effects of polysaccharide-coated insulin liposomes were investigated using the glucose oxidase method after oral administration in mice. RESULTS: The particle size of uncoated, chitosan-coated and alginate-coated insulin-liposomes was (138 +/- 31) nm, (230 +/- 20) nm and (266 +/- 19) nm, respectively. All insulin-liposomes were of spherical or ellipsoidal shape. The entrapment efficiencies were 81.6%, 73.5% and 68.7%, respectively. Insulin was protected from tryptic digestion by chitosan-coated liposomes and protected from peptic digestion by alginate-coated liposomes. The hypoglycemic effects of insulin-liposomes, coated with 0.1% chitosan and 0.1% sodium alginate, were observed. CONCLUSION: Chitosan-coated and sodium alginate-coated liposomes were shown to reduce peptic or tryptic digestion on insulin, and enhance enteral absorption of insulin.

Administration, Oral↗
PubMed2003

[Hypoglycemic effects of sodium metavanadate in diabetic mice and its effect on glucose phosphorylation].

OBJECTIVE: To investigate the effects of sodium metavanadate (SMV) on blood sugar and glucose phosphorylation in mice, and to discuss the possible mechanism of its hypoglycemic effects. METHODS: Diabetic mice (D) and control mice (V) were randomly allocated to drink SMV (0.2 mg/ml) (CV and DV groups) or NaCl (80 mmol/L) (C and V groups) respectively. The study lasted for 5 weeks. Liver glucokinase, muscle hexokinase, blood glucose and insulin were assayed at the end of each week. RESULTS: Blood glucose was higher in the diabetic groups before the administration of SMV, and the blood glucose level of group DV decreased from (18.77 +/- 1.28) to (8.94 +/- 0.94) mmol/L (P < 0.01) after oral administration of SMV for one week. While liver glucokinase increased from (1.29 +/- 0.64) to (15.36 +/- 1.57) mIU/min/mg protein and muscle hexokinase increased from (1.93 +/- 0.50) to (18.62 +/- 1.71) mIU/min/mg protein (P < 0.01) respectively. There was no continuous change of these parameters during the later weeks. No significant change of serum insulin was observed in the diabetic mice. There was a remarkable negative correlation of blood glucose level with liver glucokinase and muscle hexokinase levels. CONCLUSION: The hypoglycemic effects of SMV was independent of insulin level. In consideration of the close relations of the activities of liver glucokinase and muscle hexokinase with diabetes, and the improving of impaired glucose phosphorylation in diabetic mice by oral sodium metavanadate, which might be the mechanism of hypoglycemic effects of SMV.

Animals↗
PubMed1992

Hypoglycemic activity of some antidiabetic plants.

To assess the hypoglycemic activity mechanism of some plants used empirically by the Mexican population as antidiabetics, traditional preparations of Cucurbita ficifolia, Guaiacum coulteri, Lepechinia caulescens, and Psacalium peltatum, water, tolbutamide, and Regular Insulin were administered to three groups of rabbits each: 1. Healthy rabbits with temporary hyperglycemia induced by the subcutaneous administration of glucose. 2. Rabbits with moderate diabetes (fasting glycemia 150-300 mg/dl), induced with alloxan. 3. Rabbits with severe diabetes (fasting glycemia higher than 400 mg/dl), induced with alloxan. The plant preparations had a hypoglycemic effect similar to tolbutamide in healthy and mild diabetic rabbits and had no effect in severely diabetic rabbits. These results suggest that some pancreatic function or the presence of insulin is required for the hypoglycemic activity of these plants.

Animals↗
PubMedDate not supplied

Analgesic, antiinflammatory and hypoglycemic effects of Sutherlandia frutescens R. BR. (variety Incana E. MEY.) [Fabaceae] shoot aqueous extract.

Previous studies on the pharmacology of South African medicinal plants in our laboratories and elsewhere have shown that some plants possess therapeutic attributes. One such ethnomedically useful plant is Sutherlandia frutescens R. BR. (family: Fabaceae). S. frutescens is widely used in South African traditional medicine for the management and/or control of a plethora of human ailments. In order to scientifically appraise some of the ethnomedical uses of S. frutescens, the present study was undertaken to investigate the analgesic, antiinflammatory and antidiabetic properties of the plant's shoot aqueous extract in experimental animal models. The analgesic effect of the herb's shoot extract was evaluated using the hot-plate and acetic acid test models of pain in mice, while the antiinflammatory and hypoglycemic effects of the plant's shoot aqueous extract were investigated in rats, using fresh egg albumin-induced pedal (paw) edema, and streptozotocin (STZ)-induced diabetes mellitus. Diclofenac (100 mg/kg) and chlorpropamide (250 mg/kg) were used, respectively, as reference drugs for comparison. S. frutescens shoot aqueous extract (50-800 mg/kg i.p.) produced significant (p < 0.05-0.001) analgesic effects against thermally- and chemically-induced nociceptive pain stimuli in mice. The plant extract (50-800 mg/kg p.o. or i.p.) also significantly (p < 0.05-0.001) inhibited fresh egg albumin-induced acute inflammation and caused significant (p < 0.05-0.001) hypoglycemia in rats. The various chemical constituents and secondary metabolites of the herb are speculated to account for the observed analgesic, antiinflammatory and hypoglycemic effects of the plant. The results of this experimental animal study suggest that S. frutescens shoot aqueous extract possesses analgesic, antiinflammatory, and hypoglycemic properties, and thus lend pharmacological credence to the suggested folkloric uses of the herb in the management and/or control of painful, arthritic and other inflammatory conditions, as well as for adult-onset, type-2 diabetes mellitus in some communities of South Africa.

Analgesics↗
PubMed1975

Indolizines II: search for potential oral hypoglycemic agents.

A few 1,2-bis(N-alkylaminomethyl)indolizines, simple indolizinecarboxylic acids, and several 6-alkoxyindolizine-2-carboxylic acids were synthesized and screened as possible oral hypoglycemic agents. The absence of any significant hypoglycemic activity excludes these compounds from the predicted structural lead provided by some hypoglycemic Vinca alkaloids, such as vincamine, vindoline, and vindolinine, having the indolizine ring as one structural component. But an extension of the rationale that indolizines are also the structural components of some carcinolytic Vinca alkaloids, such as vincristine and vinblastine, used in cancer chemotherapy provided encouraging results. One indolizine derivative showed significant antineoplastic activity in Ehrlich ascites carcinoma.

Administration, Oral↗
PubMed1985

Suppression by 2-ketoisocaproate of the insulinotropic action of hypoglycemic sulfonylureas.

Tolbutamide (370 microM), gliclazide (62 microM) and glibenclamide (1 microM) failed to enhance insulin release evoked by 2-ketoisocaproate (10 mM) in rat pancreatic islets. Gliclazide also little affected insulin release evoked by 2-ketoisocaproate, whereas the hypoglycemic sulfonylurea stimulated insulin release from islets incubated in the absence of exogenous nutrient or presence of either L-glutamine, D-glucose, D-mannose, D-glyceraldehyde, L-leucine or the combination of D-glucose and pyruvate. In the presence of 2-ketoisocaproate, a modest secretory response to gliclazide was observed when the concentration of the 2-keto acid was decreased to 5 mM, or in perifused islets in which case gliclazide caused a transient increase in both 45Ca outflow and insulin output from prelabelled islets exposed to 10 mM 2-ketoisocaproate. Gliclazide and other hypoglycemic sulfonylureas failed to affect the oxidation of 2-[U-14 c]-ketoisocaproate and the latter 2-keto acid failed to affect the ionophoretic action of gliclazide in an artificial membrane model. Gliclazide increased 45Ca net uptake by islets exposed to 2-ketoisocaproate, but this effect of the sulfonylurea was much less marked than that seen in the presence of D-glucose used at a concentration of equal insulinotropic efficiency. These findings indicate that 2-ketoisocaproate impairs the cationic and secretory responses of islets to hypoglycemic sulfonylureas. It is proposed that such an impairment is compatible with the view that a remodelling of ionic fluxes in the islet cells represents a primary event in the process of sulfonylurea-stimulated insulin release.

Animals↗
PubMedDate not supplied

Binding of sulfonylurea derivatives to bovine serum albumin: part II. The relationship of binding to albumin, chemical structure, and hypoglycemic activity of sulfonamide derivatives of 2-pyrazoline-1-carboxamide.

The relationship of binding to protein and hypoglycemic activity of 11 sulfonamide derivatives of 2-pyrazoline-1-carboxamide was tested. It has been shown that the hypoglycemic effect of the most potent compound of the series, SPC-703, is related to the unbound, but not to the total concentration of the drug in the rat serum. Binding to albumin increased with the increase of hydrophobic properties of the compounds investigated. The increased affinity to albumin may be responsible for low hypoglycemic activity of some of the compounds tested.

Animals↗