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PubMed2002

Hypoglycemic and hypolipidemic effects of aqueous extract of Arachis hypogaea in normal and alloxan-induced diabetic rats.

The hypoglycemic and hypolipidemic effect of aqueous extract of Arachis hypogaea was investigated in normal and alloxan-induced diabetic rats. The extract caused a significant (P < 0.05) decrease of fasting blood glucose of both normal and alloxan-induced diabetic rats from 102.60 +/- 1.65 mg/dl to 88.79 +/- 0.94 mg/dl for normal and 189.0 +/- 30.79 mg/dl to 107.55 +/- 1.54 mg/dl for alloxan-induced diabetic rats. The extract also caused a significant (P < 0.05) decrease in serum triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol in both normal and alloxan-induced diabetic rats.

Animals↗
PubMed2006

Insulins and oral hypoglycemic agents in pregnancy.

Numerous studies have established a direct relationship between maternal levels of glycemic control and neonatal outcomes for pregnancies complicated by diabetes. The past several years have seen the addition of insulin analogues as well as many new oral agents to the pharmacological armamentarium available to treat diabetes. Insulin analogs (both rapid and long acting) are of potential interest for women with insulin-requiring diabetes because of the improved control reported in non-pregnant individuals. Insulin lispro is the only insulin analog to be systematically studied in pregnancy. At this time, the majority of evidence suggests that insulin lispro does not cross the placenta and does not have adverse maternal or fetal effects during pregnancy in women with diabetes. For women with gestational diabetes mellitus (GDM) and type 2 diabetes, which are characterized by insulin resistance and relatively decreased insulin secretion, treatment with oral hypoglycemic agents is generating much excitement. Most retrospective studies and the published clinical experience have failed to demonstrate an increased risk of neonatal hypoglycemia and other neonatal morbidities with glyburide or metformin. To date there has been only one randomized controlled trial utilizing glyburide, which found it to be safe and effective in the management of GDM. More intensive investigation regarding the safety and feasibility of oral agents in pregnancies complicated by type 2 diabetes is necessary.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Hypoglycemic effect of macrocyclic binuclear oxovanadium (IV) complex on streptozotocin-induced diabetic rats.

Though vanadium complexes mimic the action of insulin, owing to their toxicity, research is still in progress for a new vanadium complex with maximum efficacy at low concentration and without any side effects. A novel macrocyclic binuclear oxovanadium complex was synthesized, its composition and structure were confirmed by spectral studies and its efficacy was studied in streptozotocin-induced diabetic rats over a period of 30 days. The oral administration of the complex normalizes the blood glucose level in the diabetic rats and also maintains normoglycemia after a glucose load. The biochemical studies revealed that the complex is not toxic to the system. The nontoxic nature of this complex may be due to the presence of the vanadyl ions in an intact form. The study highlights the nontoxic and hypoglycemic effects of the new macrocyclic binuclear oxovanadium complex.

Animals↗
PubMed2002

Oral hypoglycemic agents in pregnancy: their time has come.

Oral agents are the mainstay of pharmacological treatment for non-pregnant women with type 2 diabetes. It has been proposed that, owing to the similarity between gestational and type 2 diabetes, some of these drugs could be used effectively and safely as alternatives to insulin therapy. This efficacious alternative provides the physician with more choices that, in turn, translate into more complex decision-making for the management of gestational diabetes. This article illustrates the pharmacological characteristics of oral hypoglycemic agents and placental transfer, provides evidence for the lack of association between congenital anomalies and the drugs, and reviews current studies and the clinical outcomes when these drugs are used.

Administration, Oral↗
PubMed2002

Alterations of lipid profile in plasma and liver of diabetic rats: effect of hypoglycemic herbs.

The effect of three species of hypoglycemic herbs (Termis, Halfa barr, or Kammun Quaramany) on the lipid profile was investigated in plasma and liver tissues of diabetic and herbs-treated diabetic rats. This profile includes total lipids (TL), triglycerides (TG), cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL). A dose of 1.5 ml of aqueous suspension of each herb/100 g body weight (equivalent to 75 mg/100 g body weight) was orally administered daily to alloxan-diabetic rats for four weeks. The present study showed 2-fold increase (p<0.05) in the plasma glucose level of diabetic rats, which received alloxan as a single dose of 120 mg/kg body weight, relative to the mean value of control group. This elevated glucose level was restored to its normal level after treatment with any one of the three herbs. Furthermore, the levels of TL, TG, cholesterol, LDL and VLDL were significantly (p<0.05) increased in the plasma and the liver tissues of diabetic rats compared to the control group, whereas HDL level was significantly (p<0.05) decreased. The plasma levels of all above parameters were normalized after treatment of the diabetic rats with Kammun Quaramany. Treatment of diabetic rats with Tennis normalized TG, cholesterol, LDL and VLDL levels, but Halfa barr restored the induced levels of plasma cholesterol, LDL and HDL to their normal levels. On the other hand, treatment with any of the three herbal suspensions could not restore the concentrations of the all tested parameters in the liver. These data demonstrated that the glycemic control of any of the three herbal suspensions was associated with their hypocholesterolemic effects on the hypercholesterolemia of the alloxan-induced diabetic rats. Moreover, the Kammun Quaramany showed the most potent effect.

Animals↗
PubMed2004

Hypoglycemic effect of Aloe vera gel on streptozotocin-induced diabetes in experimental rats.

In the present study an attempt has been made to evaluate the presence of hypoglycemic activity in the alcoholic extract of Aloe vera gel. Effects of oral administration of A. vera extract at a concentration of 200 and 300 mg/kg of body weight on (a) normal fasted rats, (b) oral glucose-loaded rats, and (c) streptozotocin-induced diabetic rats have been studied. A. vera extract maintain the glucose homeostasis by controlling the carbohydrate metabolizing enzymes.

Administration, Oral↗
PubMed2004

Beneficial effects of addition of oral spray insulin (Oralin) on insulin secretion and metabolic control in subjects with type 2 diabetes mellitus suboptimally controlled on oral hypoglycemic agents.

The aim of this study was to determine the metabolic effect and the safety of a novel oral insulin spray (Oralin) formulation at breakfast-time in subjects with type 2 diabetes with suboptimal glucose control and maintained on a combination therapy of oral hypoglycemic agents (OHAs). This was an open-label, crossover, randomized study design in subjects (n = 21) with type 2 diabetes (glycated hemoglobin A1c >8.0%). Subjects received each of the following treatments, in random order: metformin + glyburide and placebo puffs at time 0 min; or metformin + glyburide and Oralin spray (100 U) at time 0 min. Fifteen minutes later, subjects were given a standard breakfast containing 360 calories [Sustacal (Mead Johnson, Evansville, IN) liquid meal]. Blood samples were taken at regular intervals to measure serum glucose, insulin, and C-peptide. Time-averaged postprandial glucose increments (PPGIs) between 0 and 240 min were calculated for each treatment. Group mean PPGIs to OHAs versus Oralin in combination with OHAs were compared to determine the mean efficacy of the active treatment. The Oralin spray lowered the 2-h postprandial glucose rise significantly in comparison with the OHAs alone. The serum insulin levels were significantly higher with faster onset of action in the Oralin spray treatment when compared with the OHAs treatment. The reductions in C-peptides were also significantly greater in the Oralin arm than in the OHAs treatment. This study results demonstrated that Oralin could be used as meal insulin as an add-on therapy in combination with failing OHAs treatment in subjects with type 2 diabetes to regulate postprandial glucose levels.

Administration, Oral↗
PubMed2005

Effect of increased cost-sharing on oral hypoglycemic use in five managed care organizations: how much is too much?

BACKGROUND: For patients with a chronic disease, increased cost-sharing for medications may lead to unintended consequences, including reduced use of medications essential for control of their disease. OBJECTIVE: The objective of this study was to estimate the effects of small ($1-6 per 30-day supply), moderate ($7-10), and large (>$10) increases in medication cost-sharing on 12-month trends in oral hypoglycemic (OH) use among adults with type 2 diabetes. METHODS: We conducted a quasiexperimental study using a time series with comparison group design. Data were obtained from computerized membership, benefit, and pharmacy dispensing data of 5 managed care organizations (MCOs). A total of 13,110 12-month episodes of OH use and a medication cost-sharing increase ("intervention") were matched with 13,110 that had no increase. The dependent variable was OH average daily dose (ADD) standardized to each episode's mean OH ADD in the 6-month preintervention period. The principal independent variable was change in cost per 30-day OH supply between the 6-month pre- and postintervention periods. Effects of changes in cost-sharing on OH ADD were estimated using segmented time series regression. RESULTS: Episodes with >$10 increase in cost-sharing had significantly (alpha=0.05) decreased OH ADD in the postintervention period. At 6 months after this increase, OH ADD had decreased by 18.5% from that predicted from the preintervention trend. Episodes with a $1 to $10 increase in cost-sharing and those with no increase in cost-sharing had significant linear increases in OH use over the 12-month period. CONCLUSIONS: Large increases in medication cost-sharing were associated with immediate and persistent reductions in OH use. Small and moderate increases had little effect on OH use in the 6-month period after the increase.

Adolescent↗
PubMedDate not supplied

Erythrocyte aldehyde dehydrogenase and disulfiram-like side effects of hypoglycemics and antianginals.

Disulfiram-like responses to various drug therapies are caused by elevated ethnol-derived blood acetaldehyde concentrations resulting from drug-induced inhibition of aldehyde dehydrogenase enzymes. We have found that the nitrate ester antianginal drugs, isosorbide dinitrate and nitroglycerin, are potent inhibitors of human erythrocyte aldehyde dehydrogenase. To further characterize this drug-induced enzyme inhibition, erythrocyte aldehyde dehydrogenase activities were measured in patients undergoing therapy with nitrate ester antianginals (isosorbide dinitrate and nitroglycerin) and sulfonylurea hypoglycemics (chlorpropamide and tolazamide). The erythrocyte enzyme was decreased by approximately 25% in sulfonylurea-treated patients, whereas in the nitrate ester-treated patients, an 88% inhibition was observed. The minimal enzyme inhibition in the sulfonylurea-treated group was unexpected because these therapies have well-documented disulfiram-like side effects. This weak inhibition contrasted with the severe inhibition observed in the nitrate ester-treated group where the disulfiram-like side effects are not considered a serious clinical problem. This apparent anomaly was attributed to differences in inhibition of the erythrocyte and liver aldehyde dehydrogenase by the parent drugs and their hepatic metabolites.

Aldehyde Dehydrogenase↗
PubMed2005

Hypoglycemic effect of Astragalus polysaccharide and its effect on PTP1B.

AIM: To examine the effects of Astragalus polysaccharide (APS), a component of an aqueous extract of Astragalus membranaceus roots, on protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin-receptor (IR) signal transduction, and its potential role in the amelioration of insulin resistance. METHODS: Ten-week-old fat-fed streptozotocin (STZ)-treated rats, an animal model of type II diabetes mellitus (TIIDM), were treated with APS (400 mg/kg p.o.) for 5 weeks. Insulin sensitivity was identified by the insulin-tolerance test. Further analyses on the possible changes in insulin signaling occurring in skeletal muscle and liver were performed by immunoprecipitation or Western blotting. PTP1B activity was measured by an assay kit. RESULTS: The diabetic rats responded to APS with a significant decrease in body weight, plasma glucose, and improved insulin sensitivity. The activity and expression of PTP1B were elevated in the skeletal muscle and liver of TIIDM rats. Thus the insulin signaling in target tissues was diminished. APS reduced both PTP1B protein level and activity in the muscle, but not in the liver of TIIDM rats. Insulin-induced tyrosine phosphorylation of the IR beta-subunit and insulin receptor substrate-1 (IRS-1) were increased in the muscle, but not in the liver of APS-treated TIIDM rats. There was no change in the activity or expression of PTP1B in APS-treated normal rats, and blood insulin levels did not change in TIIDM rats after treatment with APS. CONCLUSION: APS enables insulin-sensitizing and hypoglycemic activity at least in part by decreasing the elevated expression and activity of PTP1B in the skeletal muscles of TIIDM rats.

Animals↗
PubMed2004

Identification of a hydroxylamine glucuronide metabolite of an oral hypoglycemic agent.

Glucuronides of piperazine hydroxylamines are rarely reported in the literature, and even more rarely are their structures unambiguously identified. One major metabolite was detected by liquid chromatography/mass spectrometry-radioactivity in urine from monkeys treated with the aryl piperazine oral hypoglycemic agent 9-[(1S,2R)-2-fluoro-1-methylpropyl]-2-methoxy-6-(1-piperazinyl) purine hydrochloride (1). The mass spectrum of this metabolite indicated that it was both monooxygenated and glucuronidated on the piperazine ring. Possible structures included the N- or O-glucuronic acid conjugates of a carbinolamine, hydroxylamine, or N-oxide. Treatment with beta-glucuronidase gave a monooxygenated derivative of the parent compound. 1H NMR analysis of either the glucuronic acid conjugate or the monooxygenated product provided insufficient evidence to unambiguously determine their structures. Incubation of 1 with pig liver microsomes resulted in formation of the same monooxygenated derivative derived from beta-glucuronidase treatment of the glucuronide metabolite. This in vitro system was used to generate sufficient material for analysis by 13C NMR, and the metabolite was identified as a hydroxylamine derivative 2. Incubation of the hydroxylamine with monkey liver microsomes and uridine diphospho-5'-glucuronic acid gave the same glucuronic acid conjugate as that observed in monkey urine. 13C NMR analysis of this biosynthetic product led to its unequivocal structure assignment as the O-glucuronic acid conjugate of the hydroxylamine 3.

Administration, Oral↗
PubMed1983

Stimulation of pancreatic polypeptide secretion in the dog by hypoglycemic agent HB 699.

HB 699 is a hypoglycemic agent that has a structural similarity to glibenclamid but does not contain the sulfonylurea group. We have studied the effects of HB 699 and the sulfonylurea glipizide on pancreatic polypeptide (PP) and insulin secretion in the dog. Both HB 699 and glipizide stimulated insulin release and caused hypoglycemia in normal dogs. The secretion of PP was stimulated by HB 699 before the onset of hypoglycemia, whereas, following glipizide administration, PP secretion increased only after the onset of hypoglycemia. As expected, in alloxan-diabetic dogs neither substance affected plasma insulin or blood glucose levels. There was, however, a stimulation of PP secretion by HB 699 that was not observed with glipizide. It appears therefore that HB 699, in contrast to glipizide, stimulates PP secretion in the absence of any changes in circulating glucose and insulin concentrations. The direct action of HB 699 on the pancreas was shown by stimulation of insulin and PP secretion in the in vitro perfused uncinate process. In view of its direct pancreatic actions, HB 699 may prove a useful tool for further study of PP secretory mechanisms.

Animals↗
PubMed1995

A new hypoglycemic agent, A-4166, inhibits ATP-sensitive potassium channels in rat pancreatic beta-cells.

Effects of a new hypoglycemic drug, N-[trans-4-isopropylcyclohexy-carbonyl]-D-phenylalanine (A-4166), on membrane current were investigated using the patch-clamp technique in single pancreatic beta-cells isolated from rats. A-4166, at a concentration of 10 microM, depolarized membrane potential of beta-cells and evoked action potentials in the presence of 2.8 mM glucose. The single ATP-sensitive K+ channel (K-ATP channel) current recorded in cell-attached membrane patches was reversibly inhibited by A-4166 (> 0.1 microM) without a change in the single-channel conductance of the K-ATP channel. Both A-4166 and tolbutamide inhibited the whole cell K-ATP channel current with half-maximum inhibition (IC50) of 0.23 and 12.8 microM, respectively (Hill coefficient = 1). In inside-out membrane patches, the IC50 with A-4166 occurred at 4.5 nM, in contrast to 0.7 microM for tolbutamide. A-4166 did not affect L- and T-type Ca2+ channels or the time-dependent outward current. We conclude that A-4166 specifically blocks the K-ATP channel and that the blockade is more potent than that of tolbutamide. The action of A-4166 underlies the mechanism by which the drug stimulates insulin secretion from beta-cells.

Adenosine Triphosphate↗
PubMed1998

Hypoglycemic effects of a novel fatty acid oxidation inhibitor in rats and monkeys.

Increased fatty acid oxidation contributes to hyperglycemia in patients with non-insulin-dependent diabetes mellitus. To improve glucose homeostasis in these patients, we have designed a novel, reversible inhibitor of carnitine palmitoyl-transferase I (CPT I) that potently inhibits fatty acid oxidation. SDZ-CPI-975 significantly lowered glucose levels in normal 18-h-fasted nonhuman primates and rats. In rats, glucose lowering required fatty acid oxidation inhibition of > or = 70%, as measured by beta-hydroxybutyrate levels, the end product of beta-oxidation. In cynomolgus monkeys, comparable glucose lowering was achieved with more modest lowering of beta-hydroxybutyrate levels. SDZ-CPI-975 did not increase glucose utilization by heart muscle, suggesting that CPT I inhibition with SDZ-CPI-975 would not induce cardiac hypertrophy. This was in contrast to the irreversible CPT I inhibitor etomoxir. These results demonstrate that SDZ-CPI-975 effectively inhibited fatty acid oxidation and lowered blood glucose levels in two species. Thus reversible inhibitors of CPT I represent a class of novel hypoglycemic agents that inhibit fatty acid oxidation without inducing cardiac hypertrophy.

3-Hydroxybutyric Acid↗
PubMed1998

Respiratory quotient in patients with non-insulin-dependent diabetes mellitus treated with insulin and oral hypoglycemic agents.

The respiratory quotient (RQ) reflects the amount of energy derived from carbohydrate as apposed to fat metabolism. To assess the metabolic state of patients with non-insulin-dependent diabetes mellitus, the RQ was measured five times a day (at 09.00, 11.00, 13. 00, 14.00, and 17.00 h) in 20 healthy subjects and 60 diabetic patients. Diabetic patients treated with insulin or sulfonylurea showed significantly higher RQ values than normal subjects and nontreated diabetic patients. Diabetic patients without treatment showed higher glucose levels, and their RQ values were significantly lower than those of treated patients. There was a significant inverse correlation between RQ and blood glucose levels at 11.00 h (r = -0.361, p < 0.01) in diabetic patients, but no significant relation with HbA1c. Treated diabetic patients with a higher body mass index tended to show a higher RQ than those with a lower one (r = -0.269, p = 0.083). Within 1 year, 7 of 13 patients, who had RQ > 1.0, gained more than 3 kg, while only 5 of the remaining 32 treated diabetic patients gained more than 3 kg (p < 0.05). This demonstrates that diabetic patients with a higher RQ tended to gain weight despite the use of insulin or oral hypoglycemia agents. The RQ increased by infusing both insulin and glucose in normal subjects. These results suggest that a high RQ results from excess insulin and excess food. The RQ is a good predictor of weight gain in diabetic patients treated with either insulin or oral hypoglycemic agents.

Calorimetry, Indirect↗
PubMedDate not supplied

The relationship between nonroutine use of insulin, food, and exercise and the occurrence of hypoglycemia in adults with IDDM and varying degrees of hypoglycemic awareness and metabolic control.

The purpose of this study was to determine objectively the relationships between changes in the usual amount of insulin injected, food eaten, and exercise performed, and the subsequent occurrence of low blood glucose (< 3.9 mM) in adults with IDDM and varying degrees of hypoglycemic awareness and metabolic control. Subjects used a handheld computer to record whether their most recent insulin, food, and exercise had been omitted or were greater than, less than, or about the same as usual following every measured blood glucose level of < 3.9 mM and > 5.6 mM. Responses for each self-management behavior were compared for the two blood glucose ranges. Food was omitted more frequently prior to a low glucose reading and exercise was omitted more frequently prior to a high glucose reading. More insulin, less food, and more exercise each were associated with low glucose levels. These findings underscore the importance of traditional diabetes education.

Adult↗
PubMed2004

Hypoglycemic and anti-lipemic effects of the aqueous extract from Cissus sicyoides.

BACKGROUND: Cissus sicyoides (Vitaceae) is a medicinal plant popularly known in Brazil as "cipó-pucá, anil-trepador, cortina, and insulina". The plant is used in several diseases, including rheumatism, epilepsy, stroke and also in the treatment of diabetes. In the present work, we studied the hypoglycemic and anti-lipemic effects of the aqueous extract prepared from fresh leaves of the plant (AECS), in the model of alloxan-induced diabetes in rats. In addition, hepatic enzyme levels were also determined. RESULTS: Results showed that the daily treatment of diabetic rats with AECS for 7 days (100 and 200 mg/kg, p.o.) significantly decreased blood glucose levels in 25 and 22% respectively, as compared to the same groups before AECS treatment. No significant changes were seen in control diabetic rats before (48 h after alloxan administration) and after distilled water treatment. While no changes were seen in total cholesterol levels, a significant decrease was observed in plasma triglyceride levels, in the alloxan-induced diabetic rats after AECS treatment with both doses, as compared to the same groups before treatment. Significant decreases in blood glucose (25%) and triglyceride levels (48%) were also observed in the alloxan-induced diabetic rats after 4 days treatment with AECS (200 mg/kg, p.o.). Aspartate (AST) and alanine (ALT) aminotransferases levels, in diabetic controls and AECS-treated rats, were in the range of reference values presented by normal rats. CONCLUSIONS: The results justify the popular use of C. sicyoides, pointing out to the potential benefit of the plant aqueous extract (AECS) in alternative medicine, in the treatment of type 2 diabetes mellitus.

Alloxan↗