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PubMedDate not supplied

Cytotoxic, hypoglycemic activity and phytochemical analysis of Rubus imperialis (Rosaceae).

Rubus imperialis, Artemia salina, 3-O-methylellagic-4'-O-alpha-rhamnose Acid Screening of different extracts, fractions and compounds from Rubus imperialis Chum. Schl. (Rosaceae) has been conduced using the brine shrimp microwell cytotoxicity assay. Three parts of the plant (methanolic extract from leaves, roots and stems), three fractions from roots (hexane, ethyl acetate and butanol) and three isolated compounds (niga-ichigoside F1, 23-hydroxytormentic acid, ellagic acid derivative) were tested. The most promising material (LC50 <1000 microg/ml) were the methanolic extract and ethyl acetate fraction from roots. However, there was little correlation observed in the degree of toxicities observed between the isolated compounds. On the other hand, the cytotoxicity and in vivo assays confirmed the hypoglycemic activity of methanolic extract and validated the Brazilian popular use of R. imperialis as an antidiabetic agent.

Animals↗
PubMedDate not supplied

Seasonal variation of kaurenoic acid, a hypoglycemic diterpene present in Wedelia paludosa (Acmela brasiliensis) (Asteraceae).

We evaluated the variation of the concentration of kaurenoic acid (1), which is a bioactive diterpene, in leaves, flowers, stems and roots from Wedelia paludosa (Acmela brasiliensis) for different seasons using the HRGC/FID method. The results indicated that the concentration of 1 is higher in the roots and stems during the autumn. The pharmacological results suggested that kaurenoic acid is responsible, at least in part, for the hypoglycemic potential detected in this plant.

Animals↗
PubMed2004

Effects of irradiance on non-structural carbohydrates, growth, and hypoglycemic activity of Rhynchelytrum repens (Willd.) C.E. Hubb. (Poaceae).

Irradiance is a crucial factor in plant development. Different radiant energy levels cause different responses related to plant growth and the production and distribution of dry matter. Considering the relationship between light availability and metabolism of carbohydrates and derived compounds, the aim of this work was to assess the effects of irradiance on non-structural carbohydrate contents and composition, as well as on the hypoglycemiant activity of Rhynchelytrum repens, a pantropical grass species popularly used for diabetes treatment. Plants of R. repens growing under natural irradiance (NI) showed increased content of total soluble carbohydrate (TSC), higher fluctuations in starch content (SC) and higher number of tillers. The flowering process of these plants was preceded by an increase in sucrose. However, their water content was low when compared to that of plants cultivated under low irradiance (LI). The ratio root/aerial organs and SC showed no significant differences in plants grown under LI, although TSC increased and a lower number of tillers were observed during the experimental period. In both conditions, sucrose was the ubiquitous sugar and seemed to be involved in the flowering process. A reduction in the blood sugar level was observed through the intra-peritoneal (IP) administration of the precipitate of aqueous extracts obtained from plants growing in both conditions of light; the supernatant fraction showed no hypoglycemic effect.

Animals↗
PubMed1983

Lipoprotein metabolism in diabetics treated with diet, oral hypoglycemic drug and insulin.

In view of the high incidence of hyperlipidemia and the low sialic acid content in the membranes of diabetics, we analyzed the percentage composition of apolipoprotein CII, known as an activator of lipoprotein lipase, and a subspecies of apolipoprotein CIII, an inhibitor of lipoprotein lipase, in triglyceride-rich lipoproteins. CIII can be sub-divided into three groups, CIII0, CIII1 and CIII2, according to sialic acid content by isoelectric focusing gel. In 82 diabetics, serum lipids and lipids in various lipoprotein fractions differed according to treatment, (diet, oral hypoglycemic drug or insulin). CIIIo/CII showed a positive correlation to plasma triglyceride and cholesterol. In the group receiving oral medication (N = 20), CIIIo/CII vs HDL-cholesterol showed a positive correlation, whereas CIII2/CII vs plasma triglyceride showed an inverse correlation. In the insulin group (N = 25), the percentage of CIIIo in VLDL apo C subspecies was inversely correlated with plasma cholesterol. In 38 diabetics whose HbA1 was also examined, CIIIo/CII increased with elevation of HbA1. CIIIo/CII in diabetics with HbA1 higher than 10% was significantly high compared with the index in other diabetics. The percentage of CIII1 in VLDL apo C subspecies was correlated to HbA1 level positively in the diet group but inversely in the insulin group. These results suggest that lipoprotein metabolism in diabetics may vary according to treatment and the sialylation of apolipoprotein may play an important role in determining the severity of this disease.

Aged↗
PubMed1977

Potentiation of hypoglycemic effect of chlorpropamide and phenfromin by halofenate.

The potentiation of oral hypoglycemic drugs by the antilipemic agent halofenate is reported. Forty-seven diabetic patients were treated for 48 weeks with halofenate, clofibrate, or placebo. Five patients in the halofenate group were taking phenformin plus either chlorpropamide or tolbutamide. Their average initial fasting plasma glucose was 160 mg./dl. All five patients experienced a slow but but substantial fall in fasting plasma glucose. The mean fasting plasma glucose for the five patients after 80 days of halofenate treatment was 63 mg./dl. As oral treatment for diabetes was reduced, the fasting plasma glucose returned to prehalofenate levels. In this study, we did ont detect an effect of halofenate on the fasting plasma glucose of diabetic patients treated with insulin or on the fasting plasma glucose levels of patients treated with diet alone.

Blood Glucose↗
PubMed1977

The effects of long-term therapy with oral hypoglycemic agents on the oral glucose tolerance test dynamics in male chemical diabetics.

The effect of fixed doses of oral hypoglycemic agents and placebo (diet alone) on the blood glucose, serum insulin, triglyceride, and cholesterol responses during oral glucose tolerance tests done annually for up to four years' follow-up was studied, in a double-blind manner, in five groups of mild male chemical diabetics. The drugs used were chlorpropamide (100 mg. O.D.), tolbutamide (500 mg. b.i.d.), phenformin (50 mg. O.D.), acetohexamide (250 mg. O.D.), and placebo. Each subject was given an individualized diet aimed at attaining and maintaining ideal weight. Comparison by chi-square analysis between the placebo group and each of the drug groups showed (a) no significant differences with regard to the number of subjects with normal glucose tolerance in each of the tests and (b) no change in the insulin secretion dynamics. Comparison between the initial test and each of the subsequent tests within each group showed (a) a greater number of subjects with normal glucose tolerance in the first follow-up test in the chlorpropamide group only, (b) no change in the insulin secretion dynamics except in the chlorpropamide group, where there was an increased insulin/glucose ratio in the first follow-up test, and (c) no change in the fasting serum triglyceride and cholesterol levels.

Acetohexamide↗
PubMed1986

Effects of oral hypoglycemic agent methylpalmoxirate on exercise capacity of streptozocin diabetic rats.

The effect of the oral hypoglycemic agent methylpalmoxirate (methyl-2-tetradecylglycidate), a selective inhibitor of long-chain fatty acid oxidation, on the exercise capacity of diabetic rats was evaluated. Rats were made diabetic by injection of streptozocin (75 mg/kg i.p.), which was confirmed by 4+ glucosuria. Daily oral administration of 2.5 mg/kg for 5 days, or a single dose of 10 mg/kg, of methylpalmoxirate produced a slight, nonsignificant decrease in the ability of diabetic rats to perform strenuous exercise of an intensity that caused exhaustion in less than 30 min. The ability of diabetic rats to perform prolonged, moderately strenuous exercise of an intensity that could be maintained for more than 60 min was not affected by methylpalmoxirate treatment. Methylpalmoxirate normalized plasma glucose concentrations, with resting glucose levels reduced 71% compared with nontreated controls, and did not cause hypoglycemia during prolonged exercise to exhaustion. Hepatic glycogen content was significantly reduced in methylpalmoxirate-treated rats in the fed, resting state, and during exercise, suggesting that liver was forced to oxidize carbohydrate at the expense of carbohydrate storage. Blood ketone levels of methylpalmoxirate-treated rats were reduced by 82% at rest, and exercise-induced ketosis was prevented by drug treatment. Muscle glycogen concentration and the rate of muscle glycogen depletion during exercise were not altered by methylpalmoxirate. It appears that the liver is the major site of action of methylpalmoxirate in diabetic rats when given in low doses.

3-Hydroxybutyric Acid↗
PubMedDate not supplied

Trends in use of oral hypoglycemic agents 1964-1986.

Oral hypoglycemic (OH) agents have been available in the United States for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) for almost 30 yr. During this time they have been subject to considerable controversy. In this article, we present pharmaceutical marketing research data that provide a review of several facets of OH use. The number of OH prescriptions dispensed peaked in 1973, decreased through 1980, and has been increasing since that year. In 1986, OH agents accounted for 21.5 million prescriptions: 1% of all prescriptions dispensed that year. Chlorpropamide is currently the most frequently ingested OH agent; it is used by 33% of the market. The two OH agents introduced in 1984, glyburide and glipizide, had acquired 41% of the OH market by the end of 1986. The rate of OH use per 1000 diabetes mellitus visits increases with patient's age. Patients aged 60 yr and older received OH prescriptions at a rate of 478 per 1000 diabetes mellitus visits in 1986. Data estimating both the number of patients diagnosed with diabetes and the number of diabetic patients taking OH agents indicate that the percentage receiving OH treatment has increased over the past 5 yr, with approximately 35% of all diabetic patients taking OH agents in 1986.

Diabetes Mellitus, Type 2↗
PubMed1996

Does a high-carbohydrate diet have different effects in NIDDM patients treated with diet alone or hypoglycemic drugs?

OBJECTIVE: To compare the effects of a nigh-carbohydrate diet on blood glucose and plasma lipids in NIDDM patients with either mild or severe glucose intolerance. RESEARCH DESIGN AND METHODS: A crossover design with a 15-day intervention diet was used. Eighteen patients were separated into two groups on the basis of hypoglycemic treatment (diet, n = 9, or diet plus glibenclamide, n = 9) and were assigned to a 15-day treatment with a high-carbohydrate/low-fiber diet containing 60% energy from carbohydrate and 20% from fat or a low-carbohydrate/low-fiber diet with 40% energy from carbohydrate and 40% from fat and then crossed over to the other diet for 15 more days. RESULTS: The high-carbohydrate diet produced a significant increase in postprandial blood glucose in patients on glibenclamide (13.6 +/- 1.4 vs. 11.0 +/- 1.8 mmol/l, P < 0.002, while no difference was recorded in the group on diet alone (9.7 +/- vs. 8.9 +/- 0.6 mmol/l). Postprandial insulin levels were significantly higher after the high-carbohydrate diet in the group on diet along (248 +/- 32 vs. 192 +/- 28 pmol/l, P < 0.01), while no significant differences were observed in the other group (226 +/- 19 vs. 202 +/- 24 pmol/l) The high-carbohydrate diet also induced a significant increase in fasting plasma triglyceride concentrations in both groups (1.36 +/- 0.2 vs. 1.12 +/- 0.2 mmol/l, P < 0.05 and 1.4 +/- 0.3 vs. 1.1 +/- 0.1 mmol/l, P < 0.05). No differences were observed in fasting plasma cholesterol and HDL. CONCLUSIONS: The effects of the high-carbohydrate diet on blood glucose control in NIDDM patients differ according to severity of glucose intolerance.

Biomarkers↗
PubMed2000

Effects of oral hypoglycemic agents and diet on protein metabolism in type 2 diabetes.

OBJECTIVE: We tested whether oral hypoglycemic agents (OHA), gliclazide with or without metformin, during an isoenergetic (ISO) and then a low-energy diet (LED) improve the altered kinetics of whole-body protein metabolism in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 13 type 2 diabetic patients (aged 51+/-2 years, weight 110+/-5 kg, BMI 41+/-1 kg/m2, fasting glucose [FSG] 11.5+/-0.9 mmol/l) (means+/-SEM) and 10 obese control subjects (48+/-3 years, 98+/-6 kg, 37+/-2 kg/m2, FSG 5.5+/-0.3 mmol/l) consumed an ISO, 1.5 g x kg(-1) x day(-1) protein for a body weight corresponding to a BMI of 25 (BMI25), a formula diet (7 days for obese control subjects, 15 days for diabetic patients), and then a 28-day LED with 50% of the energy of ISO but the same protein intake (101+/-2 g/day). OHAs were given during ISO (days 8-15) and LED. On days 6-8 (and 12-14 for diabetic subjects) of ISO and 26-28 of LED, the 60-h oral 15N-glycine method was used to obtain nitrogen flux (Q), synthesis (S), and breakdown (B). Muscle protein catabolism was estimated from N(tau)-methylhistidine (3MH) excretion. RESULTS: During ISO with hyperglycemia, Q, and B adjusted for fat-free mass, sex, and age were higher and nitrogen balance and net endogenous protein synthesis (S-B) lower than in control subjects (P<0.05). OHA decreased FSG (9+/-1 mmol/l) and 3MH and increased plasma insulin-to-glucose ratio, nitrogen retention, and S-B to levels in control subjects. The change in S-B correlated with that in FSG (r = -0.845, P = 0.001) and in fasting plasma C-peptide (r = 0.852, P = 0.0005). With LED and OHA, weight decreased 6.3 kg, glycemia reached near-normal levels, and nitrogen equilibrium was maintained; Q decreased by 7%, S and B by 11% (P<0.05) to values found in control subjects. CONCLUSIONS: OHA during ISO corrected protein turnover in relation to glycemia and plasma C-peptide. The LED maintained protein homeostasis in obese control subjects and, in diabetes patients with OHA, normalized protein metabolism. These findings have implications for diet and OHA prescription.

Blood Glucose↗
PubMed2001

Utilization of oral hypoglycemic agents in a drug-insured U.S. population.

OBJECTIVE: Clinical trials provide information regarding the safety and efficacy of medications used to manage type 2 diabetes but do not elucidate drug effectiveness in a typical managed care environment. The aim of this study was to characterize "real-world" drug utilization patterns from both a prescriber and a patient perspective. RESEARCH DESIGN AND METHODS: We conducted a retrospective analysis of a large administrative pharmacy claims database, using data on continuously pharmacy benefit-eligible members prescribed oral hypoglycemic agents (OHAs). RESULTS: The 12-month persistence rate for the OHA cohort was low, ranging from 31% for alpha-glucosidase inhibitors to 60% for metformin; compliance rates varied between 70 and 80%. During the first 12 months of therapy, 36% of the patients remaining on therapy at 12 months had one or more therapy modifications. The mean number of therapy changes increased with the length of patient follow-up, with more than half of all patients experiencing at least one therapy change over the duration of follow-up. CONCLUSIONS: These findings document the wide variation in utilization patterns associated with pharmacological management of type 2 diabetes, suggesting that opportunity exists to optimize its pharmacological management.

Carbamates↗
PubMed1987

Pharmacokinetics and metabolism of alpha-[(dimethylamino)methyl]-2- (3-ethyl-5-methyl-4-isoxazolyl)-1H-indole-3-methanol, a hypoglycemic agent, in man.

1. The pharmacokinetics and metabolism of alpha-[(dimethylamino)methyl]-2-(3-ethyl-5-methyl-4-isoxazolyl) -1H-[3-14C]indole-3-methanol, a new hypoglycemic agent, have been studied in 15 healthy male volunteers who received an oral dose of 50 or 200 mg. 2. The drug was rapidly and almost completely absorbed intact from the gastrointestinal tract. 3. Compared with the 50 mg dose, the 200 mg dose yielded less than proportionally higher blood concentrations of radioactivity and unchanged drug. This phenomenon has been observed previously in the rat and was probably due to an increase in drug distribution volume with increasing dose, since the metabolism and excretion patterns of the drug appeared to be dose-independent. 4. The drug was partially metabolized prior to excretion. Approximately 40% of the dose was recovered intact, almost exclusively in urine. The major metabolic pathway of the drug was by conjugation with glucuronic acid, while oxidation of the indole ring gave rise to a relatively minor metabolite. 5. The recovery of administered radioactivity was virtually complete within the experimental period, with a renal:faecal excretion ratio of ca 80:20. The elimination half-life of unchanged drug was 25-30 h while that of total radioactivity was 33-35 h.

Adolescent↗
PubMed1998

Hypoglycemic effect of oral insulin in diabetic rabbits using pH-dependent coated capsules containing sodium salicylate without and with sodium cholate.

The hypoglycemic effect of oral insulin (20 U and 40 U) capsules coated with a pH-dependent soluble polymer (Eudragit S100) and containing sodium salicylate (50 mg) without and with sodium cholate (50 mg) was studied in alloxan-hyperglycemic rabbits and compared with that of s.c. insulin injection (20 U). The capsules containing 20 U insulin + sodium salicylate (50 mg) produced a significant reduction in plasma glucose level to 82 and 73% of initial values at 2 and 3 hr after administration, respectively. The blood glucose level slowly returned to normal values at 5 hr. The AUC0-5 hr was 73.7 +/- 43.5 mg.hr/dl compared to 242 +/- 70.5 mg.hr/dl for insulin (20 U, s.c.) with a relative hypoglycemia of 30.4%. A higher dose of oral insulin (40 U) + sodium salicylate (50 mg) was more effective in reducing plasma glucose level which steadily decreased and reached 56% of the initial value by 5 hr (AUC0-5 hr = 132 +/- 41.5 mg.hr/dl and relative hypoglycemia = 27.3%). Sodium cholate (50 mg), however, slightly improved sodium salicylate effect producing an AUC0-5 hr of 139 +/- 37.3 mg.hr/dl with relative hypoglycemia of 28.7%. The relative hypoglycemia of pH-dependent coated capsules reached in the present experiment is the highest found so far.

Animals↗
PubMed1999

[Morning blood glucose determination in the monitoring of metabolic control in type 2 elderly diabetic cases treated by oral hypoglycemic agents].

Daily blood glucose profiles were measured in 163 Type 2 elderly diabetic cases to evaluate whether a fasting (before breakfast) or a post-prandial (after breakfast) blood glucose concentration is able to predict blood glucose values throughout the day. In the diet-treated alone group (n = 61), the percentage of daily blood glucose profiles having plasma glucose values less than the 08:00 hours (before breakfast) value were as follows: 59.0%, 32.8%, 59.0%, and 55.7% at 18.00 (before supper), 24.00, 03.00, 06.00 hours, respectively. In group treated by oral hypoglycemic agents (OHA) (n = 102), these were as follows: 45.1%, 26.5%, 52.9%, and 67.6%, respectively. In the OHA group, the mean plasma glucose value at 08:00 hours was significantly higher in patients with the lowest plasma glucose levels between 60-79 mg/dl than in patients with these levels between 80-99 mg/dl (103.7 +/- 19.6 vs 118.7 +/- 16.9 mg/dl, p < 0.01), but that at 10:00 hours was similar in the two groups (218.8 +/- 43.9 vs 214.5 +/- 40.1 mg/dl). In patients with lowest plasma glucose levels of between 60-99 mg/dl, the 08:00 hours value correlated positively with that of 24:00 (r = 0.40), 03.00 (r = 0.53), and the 06.00 hours value (r = 0.69), but no correlation was observed with the 18.00 hours value. On the other hand, the 10:00 hours value was not associated with these time-points values. Our results reveal that before breakfast plasma glucose values are more predictive of low blood glucose values in the night during sleep than after-breakfast blood glucose values, but do not predict low blood glucose values before supper in patients on OHA.

Administration, Oral↗
PubMed1997

Hypoglycemic activity of to-kai-san (Chinese medicines) in normal and KK-Ay mice.

The hypoglycemic effect of To-Kai-San (TS) was studied in normal mice, streptozotocin-induced diabetic mice, one of the animal models of insulin-dependent diabetes mellitus (IDDM) with hypoinsulinemia, and KK-Ay mice, one of the animal models of non-insulin-dependent diabetes mellitus (NIDDM) with hyperinsulinemia. TS (1,500 mg/kg) reduced the blood glucose of the KK-Ay mice from 441 +/- 36 to 285 +/- 52 mg/100 ml 7 h after a single oral administration (p < 0.001). However, no changes in blood glucose were observed in the normal and STZ-induced diabetic mice. TS also decreased the blood glucose 20 days after repeated administration to normal and KK-Ay mice. In addition, TS-treated KK-Ay mice showed decreased plasma insulin levels after both single and repeated administration. From these findings, it is believed that TS may require the presence of insulin to display its activity.

Administration, Oral↗
PubMed1998

Hypoglycemic activity of Cajanus cajan (seeds) in mice.

The effect of roasted and unroasted seeds of C. cajan on serum glucose levels of normal and alloxan diabetic mice were studied. Single doses of unroasted seeds (60% and 80%) on administration to normal as well as alloxanized mice showed significant reduction in the serum glucose levels after 1-2 hr and a significant rise at 3 hr. In case of roasted seeds, on other hand there was a significant increase in serum glucose levels during 3 hr experimental period. It is therefore concluded that roasting of seeds at high temperature for an half hour period resulted in the total loss of hypoglycemic principle but not the hyperglycemic principle present in the seeds.

Animals↗
PubMed1999

Effects of a new hypoglycemic agent A-4166 on glucose metabolism in rat adipocytes and muscle tissues.

The effects of the oral administration of a non-sulfonylurea hypoglycemic agent, the phenylalanine derivative A-4166, on serum insulin and glucose levels and glucose metabolism in isolated rat adipocytes and slices of muscle tissues were studied. An increase in serum insulin and a decrease in glucose levels were observed 30 minutes after A-4166 administration to rats fed basal or high fat diet. No changes in basal glucose transport in isolated fat cells were observed after the administration of A-4166. The effect of in vitro added insulin was, however, stronger in rats fed basal diet and treated with A-4166. An elevation of the membrane glucose transporter GLUT 4 was observed in rats treated with A-4166. An increase of basal lipogenesis, measured by incorporation of radiocarbon labeled glucose into lipids, was noted in adipocytes from rats fed high fat diet. The addition of insulin was followed by stimulation of lipogenesis in rats fed basal diet, however, this hormone had no effect in rats fed high fat diet. The administration of A-4166 did not affect the basal or insulin stimulated lipogenesis. Basal glucose oxidation in the diaphragm was not influenced by high fat diet or by A-4166 treatment. In the soleus muscle, basal glucose oxidation was decreased in rats fed high fat diet, and treatment with A-4166 increased the glucose oxidation up to values observed in the control basal diet fed rats. These results indicate that the administration of A-4166 can affect glucose metabolism in muscle tissue and the sensitivity of adipocytes to insulin.

Adipocytes↗
PubMed2000

[Mechanisms of thiazolidinedione derivatives for hypoglycemic and insulin sensitizing effects].

Ciglitazone was the first insulin sensitizer with a thiazolidinedione structure to reduce insulin resistance and hyperglycemia and many thiazolidinedione derivatives (TZDs) have since been reported as insulin sensitizers. Pioglitazone is reported to lower blood glucose through reductions in both hepatic and peripheral insulin resistance. Regarding the molecular mechanism, pioglitazone was first reported to increase the tyrosine kinase activity of the insulin receptor and then TZDs were reported to increase the insulin signal transduction. TNF-alpha causes insulin resistance through inhibition of the insulin signal transduction and TZDs have been shown to reduce insulin resistance by the suppression of the TNF-alpha gene expression. In addition, TZDs are specific agonists of PPAR gamma and the hypoglycemic effect of TZDs has been shown to involve PPAR gamma among the PPARs. Based on these observations, the molecular mechanisms of TZDs are discussed.

Animals↗