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At least 685 records · Page 38Linked to original sources
PubMed2001

A new hypoglycemic agent, JTT-608, evokes protein kinase A-mediated Ca(2+) signaling in rat islet beta-cells: strict regulation by glucose, link to insulin release, and cooperation with glucagon-like peptide-1(7-36)amide and pituitary adenylate cyclase-activating polypeptide.

A new nonsulfonylurea oral hypoglycemic agent, JTT-608, has been reported to stimulate insulin release at elevated, but not low, glucose concentrations and consequently not to induce hypoglycemia in rats. Accordingly, this drug is potentially a safer antidiabetic agent than sulfonylureas. To explore the mechanisms underlying this glucose-dependent insulinotropism, the present study investigated the effects of JTT-608 on cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and protein kinase A (PKA) activity in rat islet beta-cells by microfluorometry using, respectively, fura-2 and a fluorescence PKA substrate, DR II. In the presence of glucose at normal and elevated concentrations (5.0-16.7 mM) JTT-608 (30-1000 microM) concentration dependently increased [Ca(2+)](i) in up to 88% of single beta-cells, whereas at lower glucose concentrations (2.8 and 4.2 mM) it had little effect. The [Ca(2+)](i) responses were inhibited under Ca(2+)-free conditions and by nitrendipine, an L-type Ca(2+) channel blocker. JTT-608 rapidly activated PKA and a PKA inhibitor, H89, inhibited [Ca(2+)](i) responses to JTT-608. JTT-608 also stimulated insulin release from rat islets in a glucose- and Ca(2+)-dependent manner. The glucose-unresponsive beta-cells, which failed to respond to 8.3 mM glucose with increases in [Ca(2+)](i), were frequently recruited to [Ca(2+)](i) increases by JTT-608. JTT-608 also induced oscillations of [Ca(2+)](i). Glucagon-like peptide-1(7-36)amide (GLP-1), pituitary adenylate cyclase-activating polypeptide (PACAP), and acetylcholine (ACh) enhanced the action of JTT-608 on [Ca(2+)](i). In conclusion, JTT-608 evokes PKA-mediated Ca(2+) influx and Ca(2+) signaling in rat islet beta-cells in a glucose-regulated manner, which may account for its glucose-dependent insulinotropism. JTT-608 and neurohormones may cooperatively activate islet beta-cells under physiological conditions.

Acetylcholine↗
PubMedDate not supplied

[Hypoglycemic effect of sodium salt of monoketocholic acid in diabetic rats].

INTRODUCTION: In recent years experiments have showed that synthetic derivatives of bile acid affect blood glucose level. The aim of this work was to study the influence of sodium salt of monoketcholanate (MKH) on blood glucose level in rats with induced diabetes. MATERIAL AND METHODS: Diabetes was induced with streptozotocin applied intraperitoneally in a dose of 70 mg/kg body weight. The experiments were carried out in white laboratory rats. They were divided in two groups: group A--rats with induced diabetes (n = 10) and group B--rats with normal blood glucose level (control group, n = 10). Both groups of animals were anesthetized with urethan applied intraperitoneally in a dose of 0.75 g/kg body weight and were divided in two subgroups. The subgroups, one of each group of animals, were treated intranasally with 2% solution of MHK, in dose of 0.2 ml/kg body weight. The other two subgroups (control subgroups) received saline solution intranasally in a dose of 0.2 ml/kg body weight. Blood was taken periodically from the tail vein and blood glucose level was determined at 0, 15, 30, 45, 60, 90, 120 and 180-th minutes after treatment. RESULTS: In the group of rats with normal blood glucose level (group B) MKH did not show any statistically important changes in blood glucose level. In group of rats with induced diabetes (group A). MKH significantly decreased blood glucose level at 30, 45, 60 and 90-th minute in comparison to the diabetic rats treated with saline solution. CONCLUSION: The results of the study show that intranasally applied 2% solution of MKH has a hypoglycemic effect, but only in rats with diabetes. The same substance has no influence on blood glucose level in normoglycemic rats.

Animals↗
PubMed2001

Hypoglycemic effect of Hibiscus rosa sinensis L. leaf extract in glucose and streptozotocin induced hyperglycemic rats.

Investigations were carried out to evaluate the effect of aqueous extract of H. rosa sinensis leaves on blood glucose level and glucose tolerance using Wistar rats. Repeated administration of the extract (once a day for seven consecutive days), at an oral dose equivalent to 250 mg kg(-1), significantly improved glucose tolerance in rats. The peak blood glucose level was obtained at 30 min of glucose load (2 g kg(-1)), thereafter a decreasing trend was recorded up to 120 min. The data exhibit that repeated ingestion of the reference drug tolbutamide, a sulphonylurea and the extract brings about 2-3 fold decrease in blood glucose concentration as compared to single oral treatment. The results clearly indicate that tolbutamide improves the glucose tolerance by 91% and extract does so only by 47%. At 250 mg kg(-1), the efficacy of the extract was 51.5% of tolbutamide (100mg kg(-1)). In streptozotocin diabetic rats, no significant effect was observed with the extract, while glibenclamide significantly lowered the glucose level up to 7 hr. These data suggest that hypoglycemic activity of H. rosa sinensis leaf extract is comparable to tolbutamide and not to glibenclamide treatment.

Animals↗
PubMed2001

[Hypoglycemic effect of chitosan-microcapsulated insulin on the blood glucose level of streptozotocin-diabetic Wistar rats].

This study was conducted to observe the hypoglycemic effect of chitosan-microcapsulated insulin (insulin-microspheres) on blood glucose (BG), in diabetic rats by gavage. Using the scanning electron microscope, we observed the shape and distribution of insulin-microspheres in the tissues of liver, spleen, and small intestine of normal rats after gavage. The following groups of rats were studied: normal control rats (NC, n = 5); streptozotocin (STZ)-inducing diabetic control rats(DC, n = 6); STZ-diabetic rats treated with insulin-microsphere [120 u/kg] by gavage (DF, n = 6); STZ-diabetic rats treated with subcutaneous insulin injection [24 u NPH/kg] (DT, n = 6). Blood glucose was measured at 0-7 days after the treatments. The insulin-microspheres was found in small intestine, liver and spleen at 1, 2, 3 and 7 days. In DF group, the average blood glucose level decreased significantly from 24.7 +/- 3.2 mmol/L to 16.9 +/- 5.5 mmol/L during the first day of treatment and reached the lowest level (12.1 +/- 5.7 mmol/L) on the second day. From the third day on, the BG gradually elevated to the level before treatment; the maximum decrease of blood glucose level was 50.2%. In DT group, the average blood glucose level decreased from 25.2 +/- 3.8 mmol/L to 10.4 +/- 5.2 mmol/L during the first day of treatment and then went up gradually from the 2nd day on; the maximum decrease of glucose level was 58.7%. No significant difference was seen in maximum decrease between the two groups. These data demonstrate that oral chitosan-microcapsulated insulin has the antihyperglycemic effect on the blood glucose level of streptozotocin-diabetic rats.

Animals↗
PubMedDate not supplied

Preliminary evaluation of the hypoglycemic effect of some Brazilian medicinal plants.

The hypoglycemic effect of five Brazilian medicinal plants (Epidendrum monsenii, Marrubium vulgare, Rheedia gardneriana, Rubus imperialis and Wedelia paludosa) was studied on alloxan-induced diabetic rats. The extract of these plants was intragastrically administered to diabetic rats. The results showed that all plants studied (except R. gardneriana) significantly lowered the blood glucose. These results suggest that these four medicinal plants could be an adjuvant agent in the treatment of diabetes mellitus.

Alloxan↗
PubMed2001

Biochemical studies on hypoglycemic effect of Aavirai kudineer: a herbal formulation in alloxan diabetic rats.

Aavirai Kudineer (AK) is an herbal decoction of seven botanical drugs, cited in the Gunapadam; a Tamil Siddha medical text. The anti-diabetic efficacy of this formulation was evaluated using alloxan-induced diabetic and normal rats. Glucose tolerance was observed within 1 hr in AK-treated rats (10 ml/kg body ) as compared to control. A significant decrease in the severe hyperglycemia characteristic of alloxan diabetes was noted after 15 days of AK treatment. Further AK treatment reversed the elevated urea, creatinine, cholesterol and decreased protein values to near normal levels. Assay of glycogen content and chief carbohydrate-metabolizing enzymes, viz. hexokinase, glucose-6-phosphatase and fructose 1,6 diphosphatase in the liver of diabetic and AK-treated diabetic rats clearly ascertains the hypoglycemic efficacy of this formulation. The mode of action of this herbal formulation remains to be elucidated.

Animals↗
PubMed2002

Hypoglycemic efficacy of pulmonary delivered insulin dry powder aerosol in rats.

AIM: To observe the hypoglycemic efficacy of pulmonary delivery of insulin in dry powder aerosol form. METHODS: Insulin dry powder, made of insulin and other proper materials, was insufflated in rat lung from an incision in the throat. Meanwhile, insulin injection was administered to other rats. Glucose concentration in blood was determined in the following 7 h. The areas above the curve (AAC) of glucose concentration in blood were used to evaluate the efficacy. RESULTS: The percent minimum blood glucose levels, compared with the glucose levels before the administration, for pulmonary deliver ed insulin at the doses of 20, 10, 5, and 2.5 U/kg were 6.5 %, 16.6 %, 24.6 %, and 57.0 %, respectively. The AAC of insulin 5 U/kg by pulmonary delivery was very close to that of subcutaneous administration at the same dose. There was a linear relationship between AAC and the logarithmic dose of pulmonary delivered insulin. CONCLUSION: The pulmonary delivery of insulin acts effectively and rapidly.

Administration, Inhalation↗
PubMed2003

Pharmacodynamics, insulinotropic action and hypoglycemic effect of nateglinide and glibenclamide in normal and diabetic rats.

Control and streptozotocin-induced diabetic rats, as well as GK rats, received a single oral administration of either nateglinide (50 microg/g body wt.) or glibenclamide (1.0 microg/g body wt.). The plasma D-glucose and insulin concentrations, as well as the content of plasma, liver and pancreas in either nateglinide or glibenclamide were measured 60 min or 24 hours after the administration of these antidiabetic agents. At the 60th min, the plasma, hepatic and pancreatic content of nateglinide largely exceeded that of glibenclamide. At the 24th hour, however, the plasma concentration, as well as liver and pancreas content, of nateglinide became negligible, whilst that of glibenclamide exceeded the values recorded at the 60th min. A comparable pattern characterized the insulinotropic action and hypoglycemic effect of these two antidiabetic agents. This study thus emphasizes the vastly different pharmacodynamics of nateglinide and glibenclamide in both control and diabetic rats.

Animals↗
PubMed2000

Hypoglycemic effect of aqueous extract of Enicostemma littorale Blume (chhota chirayata) on alloxan induced diabetes mellitus in rats.

The whole plant aqueous extract of E. littorale was tested for its hypoglycemic activity on normoglycemic, hyperglycemic and alloxan induced diabetic rats. Blood sugar lowering activity was not observed in normoglycemic and glucose loaded hyperglycemic rats in the short time experiment. But in case of diabetic rats, the fall of blood sugar after 30 days treatment with the aqueous extract was found to be significant (P < 0.001). The decrease in the plasma glucose level was accompanied with decrease in the level of glycosylated haemoglobin and glucose-6-phosphatase activity in liver. The potent anti-diabetic properties of E. littorale has been reported for the first time.

Alloxan↗
PubMed1997

[Studies on hypoglycemic action of Rheum emodi].

The hypoglycemic action has been studied with the 95% ethyl alcohol extract and stilbene glycoside E (exists in a large amount), which are obtained from Rheum emodi. The experimental result shows us the utilization value of R. emodi. In the meanwhile, as tell us how to use the sect Rheum resources.

Animals↗
PubMed2002

[Hypoglycemic effect of saponin from Tribulus terrestris].

OBJECTIVE: To study the hypoglycemic effect of saponin from Tribulus terrestris L. METHOD: Alloxan was used to establish the diabetic model in mice. Phenformin Hydrochlride Tables was used as the positive control. The level of glucose, triglyceride, cholesterol and SOD in serum were determined. RESULTS: The level of serum glucose could be significantly reduced by saponin from Tribulus terrestris, which was the rate of 26.25% and 40.67% in normal mice and diabetic mice in respectively. The level of serum triglyceride could be reduced 23.35%. The saporin could also decrease the content of serum cholesterol. Serum SOD activity of the mice was increased by the saponin. CONCLUSION: Saponin from Tribulue terrestris could significantly reduce the level of serum glucose.

Animals↗
PubMed1990

[Derivatives of 2-mercaptobenzenesulphonylamide. IV. Synthesis and properties of some hypoglycemic agents derived from N-(4-chloro-2-mercapto-5-methylbenzenesulphonyl)urea].

Some new S- and N'-substituted derivatives of N-(4-chloro-2-mercapto-5-methylbenzenesulphonyl)urea were obtained. Their structures were confirmed by elemental analysis, and by IR and NMR spectra. Schemes of the reactions, their yields and some physico-chemical and pharmacological properties of the compounds are also given. N-(4-chloro-5-methyl-2-methylthiobenzenesulphonyl)-N'-R-ureas (I, II, IV) were screened for hypoglycemic activity in rats, and the results are compared to effect of tolbutamide.

Administration, Oral↗
PubMedDate not supplied

[Hypoglycemic activity of bicyclic diterpenoids of the clerodane series as compared to adebit and maninil].

Biocyclic diterpenoids--salvin, salvicin and salvifolin, administered per os to rats at a dose of 50 mg/kg show marked hypoglycemic activity in intact animals as well as in animals with experimental hyperglycemia developing against a background of GTT (3000 mg/kg intraperitoneally) or alloxan (150 mg/kg subcutaneously). They are superior to adebit but inferior to maninil. Prophylactic and therapeutic administration of these compounds ensure the preservation of islet beta-cells in animals with alloxan diabetes.

Abietanes↗
PubMed1992

Hypoglycemic effect of plants used in Mexico as antidiabetics.

The objective of this work is to investigate the hypoglycemic effect of 12 "antidiabetic" plants used in Mexico. The studies were performed using 27 healthy rabbits with the gastric administration of water, tolbutamide or decoction of the "antidiabetic" plant before the induction of temporary hyperglycemia by subcutaneous injection of 50% dextrose solution (4 ml/kg of weight) at the beginning of the experiment and after 60 min. Blood glucose was determined every 60 min for a period of 5 h. Tolbutamide and eight of the studied plants decreased significantly the hyperglycemia as compared with control test (water) (p < 0.05). The strongest effect was yielded by Guaiacum coulteri, followed by Marrubium vulgare, Crataegus pubescens, Cynodon dactylon, Calea zacatechichi, Buddleia americana, Bauhinia divaricata and Coix lachryma. The decrease of hyperglycemia caused by Physalis phyladelphyca, Pavonia schiedeana and Eucaliptus globulus was not significant (p > 0.05). Urtica dioica increased glycemia slightly.

Animals↗
PubMed1992

Hypoglycemic effects of Coccinia indica: inhibition of key gluconeogenic enzyme, glucose-6-phosphatase.

Coccinia indica (Family: Cucurbitaceae, locally known as telakucha) leaves were extracted with 95% ethanol. Following evaporation of the solvents, the residue was suspended in distilled water. When this suspension was fed orally to male normal-fed and 48-hr starved rats, the blood glucose was lowered 21% (P less than 0.01) in normal-fed and 24% (P less than 0.001) in 48-hr starved animals respectively. Starvation had induced a 3-fold increase in the activity of glucose-6-phosphatase and this activity was depressed 19% (P less than 0.05) by extract feeding while basal activity of the enzyme in normal-fed rats remained unaffected. Consistent with the depression of glucose-6-phosphatase, urea cycle enzyme arginase was also depressed 21% (P less than 0.001) and 12% (P less than 0.01) in the liver of 48 hr-starved and normal-fed animals respectively. Unlike glucose-6-phosphatase, starvation induced levels of gluconeogenic enzymes alanine aminotransferase and aspartate aminotransferase were not affected by Coccinia extract. These results suggest that the hypoglycemic effect of C. indica is partly due to the repression of the key gluconeogenic enzyme glucose-6-phosphatase.

Animals↗
PubMed1992

[Insulin secretion and sensitivity in patients with secondary failure to oral hypoglycemic drugs].

Secretion and peripheral sensitivity to insulin was investigated in diabetic patients with secondary failure to oral hypoglycemic drugs. 8 patients with secondary failure (non responders), 7 non insulin dependent diabetic patients with good response to oral drugs (responders) and 8 control subjects were studied. Insulin secretion was determined with peptide C in urine obtained 4h after a 500 Cal breakfast; in vivo insulin sensitivity was studied by the euglycemic hyperinsulinemic clamp technique. All groups were comparable in age, nutritional status and duration of diabetes. Non responders had higher fasting blood sugar levels compared to responders (228 +/- 70 vs 136 +/- 21 mg/dl, p < 0.05). Controls had lower blood sugar levels than the other 2 groups (93 +/- 8, p < 0.05). Insulin levels were similar in non responders and responders (24 +/- 12 and 16 +/- 9 uU/ml, respectively) and higher than in controls (10 +/- 3, p < 0.05). Peptide C was lower in non responders than in responders (3.8 +/- 1 vs 5.3 +/- 1.4 nm/4h, respectively, p < 0.04), but similar to controls (4.4 +/- 1.2). No difference in secretion of insulin was noted between non responders and responders. Insulin sensitivity index was 3.67 +/- 1.41 ((mg/kg.min)/(uU/ml)). 100 in non responders and 4.20 +/- 1.14 in responders; the index for controls was 7.92 +/- 1.70 (p < 0.05). These results show that non responders have normal insulin levels, although inappropriate for the level of hyperglycemia. Insulin sensitivity in non responders is similar to responders but lower than controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Oral hypoglycemic agents? Negative.

I am convinced that oral hypoglycemic therapy is associated with increased cardiovascular mortality. But the more important issue is whether the benefits of these agents are worth the risk.

Attitude of Health Personnel↗
PubMed2003

The safety of oral hypoglycemic agents in the first trimester of pregnancy: a meta-analysis.

OBJECTIVE: To examine the relationship between first-trimester exposure to oral hypoglycemic agents (OHAs), congenital anomalies and neonatal mortality, accounting for the potential confounding effect of maternal glycemic control. METHOD: A meta-analysis was conducted by searching the literature for studies reporting on women with type II diabetes mellitus, first-trimester exposure to OHAs and either major malformations and/or neonatal mortality. Glycemic control monitoring was noted. Studies were reviewed by two reviewers and disagreement was resolved by consensus. Odds ratios and risk differences were calculated to determine the risk of major malformations and neonatal mortality between those exposed and those not exposed to OHAs. RESULTS: Ten studies met the inclusion criteria. There was no significant difference in the rates of major malformations between those exposed and those not exposed to OHAs; the odds ratio was 1.05 (95% CI 0.65 to 1.70) and the risk difference was 0.00 (95% CI -0.03 to 0.03). For studies reporting glycemic control, the odds ratio for major malformations between those exposed and those not exposed to OHAs was 1.06 (95% CI 0.62 to 1.81). For neonatal death, the odds ratio was 1.16 (95% CI 0.67 to 2.00) and the risk difference was -0.03 (95% CI -0.17 to 0.12). The studies did not provide sufficient detail to determine which OHA(s) were associated with adverse neonatal outcomes. CONCLUSIONS: First-trimester exposure to OHAs did not significantly increase rates of major malformations or neonatal death. However, the studies were heterogeneous and care must be taken in interpreting the results. Further studies are needed to address the safety of OHAs in the first trimester with concomitant good glycemic control.

Abnormalities, Drug-Induced↗