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[Development of body weight during antidiabetic treatment].

Antidiabetic treatment of persons with type I or 2 diabetes mellitus is usually accompanied by body-weight gain. This is because any improvement in metabolism is associated with a decrease in glycosuria: Long-persisting loss of calories via urine is decreased. Furthermore, insulin has an antilipolytic effect simulates lipogenesis and promotes fluid retention. Hypoglycemia always necessitates additional intake of carbohydrates and thus also favors weight gain. During antidiabetic treatment with metformin the increase in body weight is significantly less than during treatment with sulphonylurea compounds or insulin. For this reason metformin is the drug of choice in the antidiabetic treatment of overweight diabetics. It is also superior to all other drugs when given together with insulin. The best results of insulin treatment with regard to weight control are obtained with basal insulin combined with metformin rather than insulin alone, prandial insulin substitution or intensified insulin treatment. If the aim is weight reduction, the pharmacokinetics of short-acting insulin analogs makes adaptation of insulin dose to reduced food intake easier than normal insulin. More attention than has previously been the case should be paid from the start to measures that prevent weight gain when planning antidiabetic treatment: prevention of weight gain is easier to achieve than weight reduction.

Diabetes Mellitus, Type 2↗

"Syndrome malin"-like symptoms probably due to interaction between neuroleptica and oral antidiabetic agents.

In two cases of chronic schizophrenia complicated by diabetes mellitus, the concomitant use of the neuroleptica and oral antidiabetics was attended by the appearance of symptoms simulative of syndrome malin, i.e. hyperpyrexia, tachycardia, blood pressure instability, disturbances of consciousness, muscle rigidity, tremor, dysphagia, salivation and urinary incontinence. In one of these cases, the patient, a 47-year-old man, died 10 days later. In the other case, a 62-year-old woman, almost all the symptoms subsided after 14 days, and oral dyskinesia persisted for only one additional month. In both cases, hypoglycemia due to oral antidiabetics was not seen. In Case 2, a combined regimen of oral antidiabetics and neuroleptica was later resumed. Again, a similar set of symptoms as seen initially were noted, along with an elevation of the serum CPK level. Parenterally administered biperiden proved to be highly effective in the control of the symptoms. The pathogenetic mechanism of these symptoms might possibly be explained as potentiation of the action of the neuroleptica by oral antidiabetics.

Consciousness Disorders↗

Comparison of pioglitazone with other antidiabetic drugs for associated incidence of liver failure: no evidence of increased risk of liver failure with pioglitazone.

AIM: The aim of this study was to assess the incidence of liver failure in association with antidiabetic treatment using pioglitazone vs. other oral antidiabetic medications. METHODS: The study was a retrospective analysis of claim data from the PharMetrics Patient-Centric Database that had over 1.12 million enrollees with type 2 diabetes. All patients, > or =18 years of age with type 2 diabetes, who had initiated treatment either with a thiazolidinedione (pioglitazone and rosiglitazone), sulfonylurea or metformin were identified and matched on the basis of propensity scores, which served as a proxy for severity of disease. The primary measure of interest was the incidence of liver failure or hepatitis post-index date. In addition to unadjusted comparisons, Cox proportional hazard models were employed to estimate the risk of developing liver failure or hepatitis. RESULTS: There was no significant difference in the 1- and 2-year incidence rates of liver failure or hepatitis (primary and secondary diagnoses) between the pioglitazone monotherapy group and the respective comparator groups. In Cox proportional hazard models controlling for age, pre-index total healthcare costs, Charlson comorbidity index, procedures and a hospitalization or Emergency room (ER) visit for pre-index hyperglycaemia, and pioglitazone were not associated with an increased risk of liver failure or hepatitis, compared to all other defined groups. Furthermore, no primary or secondary diagnosis of liver failure was reported in the pioglitazone group during the follow-up period. CONCLUSIONS: Results of retrospective data analysis demonstrate no evidence of increased risk of liver failure or hepatitis for patients initiating therapy on pioglitazone, compared to other oral antidiabetic agents. Pioglitazone therapy was not associated with an increased risk of liver failure at 2 years relative to other oral antidiabetic therapies.

Administration, Oral↗

Use of antidiabetic and antihypertensive drugs in hospital and outpatient settings in Hong Kong.

OBJECTIVE: To investigate the usage patterns of antidiabetic and antihypertensive drugs and to identify any discordance between recommended management guidelines and clinical practice in two study locations. DESIGN: Prescription survey. SETTING: A government- operated general outpatient clinic (GOPC) and a medical/geriatric specialist clinic (SC) affiliated with a regional hospital in the same district. PATIENTS: Patients presenting with a prescription during the study period at the respective pharmacy were classified as having diabetes if at least one antidiabetic agent was prescribed and as having hypertension if a cardiovascular drug was prescribed in a hypotensive dosage. MAIN OUTCOME MEASURE: The pattern of use of antidiabetic and antihypertensive drugs. RESULTS: One thousand one hundred forty-four consecutive prescriptions were collected in the GOPC, and 1523 in the SC. Of 9.4% (n = 107) of patients were classified as having diabetes in the GOPC and 20.4% (n = 310) in the SC (p<0.001). Most patients with diabetes were taking oral hypoglycemic agents (98.1% in GOPC vs. 84.5% in SC). Glibenclamide was the sufonylurea used most often as monotherapy in both settings (50.5% in GOPC vs. 40.6% in SC). The combined use of a sulfonylurea with metformin was common in both settings (22.4% in GOPC vs. 28.4% in SC). Metformin monotherapy (1.9% in GOPC vs. 2.6% in SC) and combination treatment of insulin with an oral agent (0% in GOPC vs. 2.6% in SC) were rarely prescribed. In the GOPC, 24.5% (n = 280) of patients were prescribed an antihypertensive drug compared with 47.1% (n = 717) in the SC (p< 0.001). In the GOPC, the use of antihypertensive drugs was more prevalent in those with diabetes (53.5%) than in the remaining patients without diabetes (21.5%, p<0.001). In the SC, 51% of patients with diabetes were receiving antihypertensive drugs, but 40% of patients without diabetes were also receiving three treatments. In the GOPC, diuretics (indapamide 14.3% other 59%) and methyldopa (9.5%) were the most frequent choices of antihypertensive drugs when used as monotherapy in subjects without diabetes. In the SC, apart from diuretics (indapamide 12.9%, other 20.3%), beta-blockers (29%) also were prescribed frequently. If treated with only one antihypertensive drug, most patients with diabetes in the GOPC were prescribed indapamide (72.7%), and patients in the SC were treated mainly with angiotensin-converting enzyme inhibitors (35%) indapamide (22.5%), or calcium-channel blockers (13.8%). CONCLUSIONS: In this prescription-based survey, diabetes mellitus and hypertension were found to be common diseases in general practice and in a hospital SC. Oral hypoglycemic agents were the main from of antidiabetic therapy in both settings, with glibenclamide being the most commonly prescribed sulfonylurea. The types of antihypertensive drugs used were different in the two locations and varied according to the coexistence of type II diabetes mellitus. Despite some potential limitations, prescription-based surveys are an easy and economical method for surveying the occurrence of some common medical problems and the pattern of drug use in a fairly large number of patients in health institutions.

Adult↗

Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-gamma: binding and activation correlate with antidiabetic actions in db/db mice.

The thiazolidinediones are novel insulin sensitizers that serve as orally active antidiabetic agents, in rodents, nonhuman primates, and man. We have examined the effects of 4-week oral administration of three thiazolidinediones (AD-5075, BRL 49653, and CS-045) on plasma glucose and triglyceride concentrations in obese hyperglycemic db/db mice. All three agents lower plasma glucose and triglyceride concentrations. Normal levels of glucose are achieved after treatment with AD-5075 (> 1.7 mg/kg) or BRL 49653 (> or = 30 mg/kg), whereas CS-045 (100 or 300 mg/kg) produces only modest reductions in either parameter. Although the thiazolidinediones have demonstrated insulin-sensitizing activities both in vivo and in vitro, their primary molecular target has been unclear. We have compared the in vivo antidiabetic actions described above with the in vitro activities on peroxisomal proliferator-activated receptor-gamma (PPAR gamma). Hamster PPAR gamma 1 was transiently expressed in COS-1 cells to study the binding of [3H]AD-5075. The concentrations of compounds needed to displace radiolabeled AD-5075 from PPAR gamma correlate with their in vivo potency; the Ki values for displacement by cold AD-5075, BRL 49653, and CS-045 are 22, 68, and 1600 nM, respectively. To examine activation of the receptor, it was transiently cotransfected into COS-1 cells with a reporter plasmid containing two copies of a peroxisome proliferator response element. The EC50 values for activation are 2, 6, and 140 nM for AD-5075, BRL 49653, and CS-045, respectively. We have also analyzed limited proteolytic digests of in vitro translated hamster PPAR gamma. The thiazolidinediones produce a conformational change in PPAR gamma analogous to those produced by agonists of other nuclear hormone receptors. In the presence of saturating concentrations of either AD-5075 or BRL 49653, a receptor fragment of 27 kDa is protected from proteolysis by trypsin. These data support the conclusion that the antidiabetic actions of the thiazolidinediones are directly mediated through binding to PPAR gamma and the resulting active conformation of the receptor. Therefore, binding and transactivation assays using PPAR gamma should serve to identify other novel therapeutic agents with potential antidiabetic activities.

Animals↗

Toxicology of oral antidiabetic medications.

PURPOSE: The toxicology of oral antidiabetic agents is reviewed. SUMMARY: Type 2 diabetes mellitus is increasing to near epidemic proportions, with a reported 190 million patients worldwide. Use of oral antidiabetic medications is increasing along with a proportional increase in adverse events. Oral antidiabetic medications can be separated by mechanism of action into two groups: hypoglycemics (sulfonylureas and meglitinides) and antihyperglycemics (biguanides and alpha-glucosidase inhibitors). The hypoglycemic agents pose a significant risk of morbidity, mortality, and permanent sequelae secondary to prolonged periods of hypoglycemia. However, outcomes are routinely good if intervention is initiated early, with the primary goal return of euglycemia using supplemental dextrose infusion and octreotide to reduce further insulin secretion. Metformin-associated lactic acidosis (MALA) can occur with both acute and chronic metformin exposure. While MALA is not common, its associated rates of morbidity and mortality can be high. Secondary to MALA, the patient may experience changes in the central nervous system, cardiovascular collapse, renal failure, and death. The primary goals of therapy are restoration of acid-base status and removal of metformin, using hemodialysis and bicarbonate therapy. There is no specific antidote for MALA. The alpha-glucosidase inhibitors and thiazolidinediones pose minimal risk of adverse events in acute overdose. However, acarbose and all thiazolidinediones have been reported to produce hepatic injury with chronic therapy. Cessation of therapy with the offending agent and supportive care are the mainstays of overdose management with these drugs. CONCLUSION: The toxicity of oral antidiabetic agents differs widely in clinical manifestations, severity, and treatment.

Diabetes Mellitus, Type 2↗

Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect.

OBJECTIVE: Thiazolidinediones (TZDs), a class of insulin-sensitizing agents used clinically to treat type 2 diabetes, are also antiatherogenic. This study was designed to elucidate the relationship between the antiatherogenic and antidiabetic effects of pioglitazone, a TZD, in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 136 Japanese type 2 diabetic patients were included and divided into two groups: the pioglitazone-treated group (30 mg daily for 3 months) (n = 70) and the untreated control group (n = 66). The changes in glycolipid metabolism as well as plasma high-sensitivity C-reactive protein (CRP), leptin, adiponectin, and pulse wave velocity (PWV) were monitored to analyze the relationship between the antiatherogenic and antidiabetic effects of pioglitazone. RESULTS: The pioglitazone treatment significantly reduced hyperglycemia, hyperinsulinemia, and HbA(1c) levels and increased plasma adiponectin concentrations relative to the control group (P < 0.01). It also significantly decreased CRP and PWV (P < 0.01). The antiatherogenic effect was observed in both the nonresponders showing <1% of reduction in HbA(1c) (n = 30) and responders showing >1% of reduction (n = 40). ANCOVA revealed that treatment with pioglitazone was associated with a low CRP and PWV, independent of the changes in parameters related to glucose metabolism. CONCLUSIONS: This study represents the first demonstration of the antiatherogenic effect of pioglitazone in both nonresponders and responders with respect to its antidiabetic effect and suggests that pioglitazone can exert its antiatherogenic effect independently of its antidiabetic effect.

Adiponectin↗

Treatment of type 2 diabetes: inadequate assessment of oral antidiabetic combinations.

(1) Metformin and glibenclamide are the only oral antidiabetics with a proven impact on the complications of type 2 diabetes. (2) Treatment with one of these drugs often fails to achieve the recommended target in HbA1c level (below 7%). (3) Only one randomised trial has assessed the preventive efficacy of a combination of oral antidiabetics when hyperglycaemia persists despite treatment with a glucose-lowering sulphonylurea. The trial showed that combining metformin and a glucose-lowering sulphonylurea is associated with a higher mortality than therapy with a sulphonylurea alone. (4) Despite this result, most clinical guidelines recommend the metformin + glucose-lowering sulphonylurea combination when oral antidiabetic monotherapy fails. (5) In the absence of convincing data supporting any particular strategy, all options should be discussed with patients including continuing with oral antidiabetic monotherapy, or starting insulin.

Clinical Trials as Topic↗

[Trends in prescribing oral antidiabetic drugs. An analysis of the Berlin diabetes register covering 28 years].

On the basis of the data collected by the (East) Berlin diabetes register, the prevalence of diabetes and trends in the prescription of oral antidiabetic agents over almost three decades were analysed. Between 1961 and 1989, the diabetic registration rate increased threefold, from 13,700 to 49,000. This corresponds to an increase in prevalence from 1.3% to 3.8%. At the beginning of the nineteen-sixties, only carbutamide and tolbutamide were prescribed, the respective percentages being 29% and 71%. From 1969 onward, the percentage of carbutamide decreased drastically and was no longer prescribed after 1973. With the introduction of the sulfonylureas ureas of second generation in 1969, the prescription of tolbutamide and glibenclamide showed an inverse evolution. In 1989, the prescription rate of tolbutamide was only 10% of all oral antidiabetics, while 88% of the patient group received glibenclamide. Since 1965, biguanides have been increasingly prescribed, reaching a peak of 32% of all prescriptions of oral diabetics by 1975. Thereafter, prescription of biguanides decreased. In 1979, biguanides accounted for only about 5% of all oral antidiabetics prescribed, and in 1989, for only 0.3%. The introduction of structured dietary teaching programs for type 2 diabetics resulted in a drastic change in the prescription of oral diabetics in the case of newly diagnosed patients: in 1968, primary management with oral antidiabetics peaked, accounting for 43.2% of the cases (newly diagnosed diabetics 3.049). This percentage decreased progressively and, in 1985, reached a figure of 17.5% in new cases of diabetes (total number of newly diagnosed cases 3.936). Since 1975, the percent of cases managed primarily with insulin has remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Berlin↗

Polypharmacy with oral antidiabetic agents: an indicator of poor glycemic control.

OBJECTIVE: To evaluate antidiabetic drug treatment patterns and glycemic control among patients diagnosed with type 2 diabetes mellitus. STUDY DESIGN: Retrospective study using the automated databases of a 200 000-member HMO. METHODS: The study population consisted of patients > or =18 years of age with documented type 2 diabetes mellitus from January 1, 2002, through December 31, 2002. We determined the proportion of patients who had optimal glycemic control (glycosylated hemoglobin <7%) during the 6 months after the initial documentation of diabetes during calendar year 2002 (index date). RESULTS: Of the 4282 patients who met the inclusion criteria, 1050 (25%) received 1 oral agent, 486 (11%) received 2 oral agents, 56 (1%) received > or =3 oral agents, 84 (2%) received insulin and an oral agent, and 107 (2%) received insulin exclusively within 90 days after the index date. Among the 1075 patients receiving antidiabetic drug therapy who had a laboratory test result documented, 414 (39%) had optimal glycemic control. Optimal control was most frequent among patients receiving 1 oral agent (47%) and least frequent among patients receiving > or =3 oral agents (13%) (P <.01). Patients with a prior history of suboptimal glycemic control were less likely to have optimal glycemic control. CONCLUSIONS: Multiple oral antidiabetic agents may serve as a marker for more severe, uncontrolled diabetes. The vast majority of patients treated with multiple oral antidiabetic agents had suboptimal glycemic control, suggesting a need for intensified efforts to treat this particular group of patients to recommended goal levels.

Administration, Oral↗

Studies on the phototoxic effects of oral antidiabetics and diuretics.

A number of sulphonamide derived oral antidiabetics (chlorpropamide, glibenclamide, glipizide, gliquidone, glymidine, tolazamide and tolbutamide) and diuretics (bemetizide, bendroflumethiazide, benzylhydrochlorothaizide, bumetanide, butizide, chlortalidone, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide and xipamide) were investigated for phototoxicity in a cell culture model. Cell death dependent on UVA fluence and test substance concentration was observed in the presence of the oral antidiabetics glibenclamide and gliquidone, as well as the diuretics bemetizide, bendroflumethiazide, benzylhydroxhlorothiazide, bumetanide, butizide, hydrochlorothiazide, hydroflumethiazide, piretanide, polythiazide and trichlormethiazide. Bendroflumethiazide was phototoxic at 5 x 10(-5) mol/l and higher concentrations, bemetizide, benzylhydrochlorothiazide, bumetanide and hydroflumethiazide were phototoxic at 2.5 x 10(-4) mol/l and higher concentrations, and the oral antidiabetics glibenclamide and gliquidone as well as the diuretics butizide, hydrochlorothiazide, piretanide, polythiazide and trichlormethiazide were phototoxic at 5 x 10(-4) mol/l and higher concentrations. The oral antidiabetics chlorpropamide, glipizide, glymidine, tolazamide and tolbutamide as well as the diuretics chlortalidone, furosemide, indapamide and xipamide did not induce phototoxicity in this assay.

Carcinoma in Situ↗

Beta-agonists as antiobesity, antidiabetic and nutrient partitioning agents.

In the past decade, the antiobesity, antidiabetic and nutrient partitioning activities of beta-agonists have been extensively studied. The data generated from these compounds in experimental and farm animals have convincingly proved that body fat content and body weight can be modified to some degree by a metabolic agent without decreasing food consumption. Marginal antiobesity and antidiabetic activities in humans have been demonstrated with a few mixed beta-agonists under certain conditions, but their utility is limited by side effects. The concept of a beta 3-receptor rose from the study of these compounds and has been verified by the cloning and expression of this receptor from several species. Rat beta 3-selective agonists have so far shown no antiobesity efficacy in humans. The resolution of several issues is critical for the discovery and development of efficacious antiobesity and antidiabetic agents with minimum side effects. Ultimately, the further investigation of these beta-agonists and beta-receptors should lead to a better understanding of the relationship between energy metabolism and feeding behavior.

Adrenergic beta-Agonists↗

Three different classes of oral antidiabetic drugs do not increase insulin binding and insulin-induced RNA synthesis in human fibroblast cultures.

We describe insulin binding and insulin-mediated RNA synthesis on seven human fibroblasts strains in culture initiated from skin biopsies in the presence of three oral antidiabetic agents, Metformin, Gliquidone, and a non-sulfonylurea antidiabetic drug (B X DF 591 ZW), which belong to different chemical classes. At least at a nontoxic pharmacologic concentration of 1 microgram/ml these drugs did not influence the number and affinity of insulin receptors, nor did they increase the insulin-mediated RNA synthesis. We conclude that cultured fibroblasts do not represent the proper target for an evaluation of an extrapancreatic action of oral antidiabetic drugs.

Cells, Cultured↗

Morning or bed-time insulin with or without glibenclamide in elderly type 2 diabetic patients unresponsive to oral antidiabetic agents.

We studied in a group of elderly (mean age 77 yr) non-obese Type 2 diabetic patients (n = 9) in a randomised, placebo-controlled prospective cross-over study of 8 months duration, the effects of substituting maximal sulfonylurea medication with a single injection of human zinc insulin taken either at bedtime (BTI) or morning (MI). All patients were poorly controlled with oral antidiabetic agents. After a 2-month regimen with either BTI or MI, a glibenclamide (GL, 3.5 mg/day) was given for an additional 2 months. Both insulin regimens decreased mean diurnal blood glucose and glycosylated HbA1c values to a similar extent (2.6-2.7%; p < 0.01-0.05), but with a lower daily insulin dose with BTI (0.30 +/- 0.03 IU/kg) as compared with MI (0.39 +/- 0.05 IU/kg; p < 0.01). A further improvement in metabolic control was observed in both groups after the introduction of GL; the mean reduction in glycosylated HbA1c was 1.4% for BTI and 0.7% for MI (p < 0.01 and 0.05, respectively), In conclusion, a subgroup of poorly controlled elderly Type 2 diabetic patients showed an improvement in metabolic control after a single injection of insulin despite discontinuation of maximal doses of oral antidiabetic agents. After 2 months of insulin treatment, a further improvement was achieved by a low dose of sulfonylurea in these patients who were formerly considered unresponsive to oral antidiabetic agents.

Aged↗

Pharmacodynamic-pharmacokinetic profiles of metformin hydrochloride from a mucoadhesive formulation of a polysaccharide with antidiabetic property in streptozotocin-induced diabetic rat models.

The antidiabetic property of a formulation containing metformin hydrochloride and detarium gum has been evaluated in streptozotocin model of experimental rats. Both the gum and metformin hydrochloride possess antidiabetic properties to varying degrees. The pharmacokinetics of metformin from the mucoadhesive dosage forms indicated that for metformin alone, the area under the curve (AUC) values were 125.6 and 135.6 mgh/ml at 200 and 400 mg/kg BW, respectively. For the mucoadhesive products using the same dose levels, the AUCs were modified to 102.4 and 150.2 in detarium gum and 59.9 and 80.4 in NaCMC. The results indicate that detarium gum is a good excipient for the formulation of metformin mucoadhesive delivery systems when compared with NaCMC. The gum also showed promising antidiabetic effect and should be cautiously used as it may lead to depressed blood-glucose levels beyond the desired levels.

Adhesiveness↗

Clinical usage of hypolipidemic and antidiabetic drugs in the prevention and treatment of cancer.

Factors predisposing hormone-dependent tissues to the development of tumors coincide, at least partly, with hormonal-metabolic promoters (like insulin resistance, glucose intolerance, visceral obesity, etc.) of other main non-communicable diseases. This important knowledge poses the question of whether the same approach which is applied for prevention/treatment of a metabolic syndrome and the associated endocrine disorders might also be used in preventive and therapeutic oncology. Whereas an answer to this question remains controversial and is based mainly on experimental evidence, there is accumulating clinical data suggesting a practical significance of such a strategy, even though it is not to be considered as directly cytostatic. Among the many drugs under discussion, three groups of medicines (statins, antidiabetic biguanides, and thiazolidinediones) are the most attractive. The concept of metabolic rehabilitation is proposed and used practically in an adjuvant setting for the correction of the above-mentioned endocrine-metabolic disorders commonly found in cancer patients. The current use and aim of this approach is to improve the survival of patients and limit cancer progression. Nonetheless, it also appears potentially useful as a neoadjuvant therapy as well as a prophylactic treatment earlier in life for specific groups of people with hormone-associated enhanced oncological risk. It seems possible that certain hypolipidemic and antidiabetic medicines with pleiotropic effects might be combined with traditional antisteroid prevention/therapeutic approaches in routine clinical situations as well as for overcoming resistance to standard cancer hormonal therapies including receptor-negative cases. Characteristic at the end of the 20th and at the beginning of the 21st century is an epidemic of diabetes and obesity, which might further increase the incidence of certain cancers. This makes it timely to apply hypolipidemic and antidiabetic drugs (in combination with reasonable dieting, increased physical fitness, and an in-depth knowledge of drug-gene interactions) as an approach warranting further study.

Chemoprevention↗

Hypoglycaemic and antidiabetic activity of acetonic extract of Vernonia colorata leaves in normoglycaemic and alloxan-induced diabetic rats.

The aqueous extract of Vernonia colorata (Willd.) Drake (Composeae) leaves is used by African traditional medicine practitioners as a remedy for the treatment of diabetes. Our previous studies have shown the hypoglycaemic activity of the aqueous extract of Vernonia colorata leaves (300 mg/kg, per os) in normoglycaemic rats. The aim of the present study was to investigate the hypoglycaemic and antidiabetic activity of acetonic and hexanic extracts of the leaves of Vernonia colorata in order to further discriminate the type of extract which provides a better antidiabetic activity. Experiments were performed in normoglycaemic and alloxan-induced diabetic rats. The acetonic extract of the leaves of Vernonia colorata (AELVC) (100 mg/kg, per os) induced a significant decrease of blood glucose in normoglycaemic rats. The glycaemia varied from 4.72+/-0.11 to 3.72+/-0.22 mmol/l (p<0.05, n=5) 3 h after AELVC administration per os. In contrast, the hexanic extract of the leaves of Vernonia colorata (HELVC) increased significantly the glycaemia in normoglycaemic rats. Like glibenclamide, AELVC has an antihyperglycaemic effect in oral glucose tolerance test (OGTT) and alloxan-induced diabetic rats. These results have shown that: (i) AELVC and HELVC have an opposite effect on basal blood glucose in normoglycaemic rats, suggesting that the mechanisms of action of both above-mentioned extracts are different; (ii) AELVC has also an antidiabetic activity in hyperglycaemic rat models.

Acetone↗

Antinociceptive, anti-inflammatory and antidiabetic effects of Bryophyllum pinnatum (Crassulaceae) leaf aqueous extract.

In order to scientifically appraise some of the ethnomedical uses of Bryophyllum pinnatum leaves, the present study was undertaken to investigate the antinociceptive, anti-inflammatory and antidiabetic properties of the plant's leaf aqueous extract in experimental animal models. The antinociceptive effect of the herb's leaf extract was evaluated by the 'hot-plate' and 'acetic acid' test models of pain in mice. The anti-inflammatory and antidiabetic effects of the plant's extract were investigated in rats, using fresh egg albumin-induced pedal (paw) oedema, and streptozotocin (STZ)-induced diabetes mellitus. Diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used respectively as reference drugs for comparison. Bryophyllum pinnatum leaf aqueous extract (BPE, 25-800 mg/kg i.p.) produced significant (P<0.05-0.001) antinociceptive effects against thermally- and chemically-induced nociceptive pain stimuli in mice. The plant extract (BPE, 25-800 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) hypoglycaemia in rats. The results of this experimental animal study suggest that Bryophyllum pinnatum leaf aqueous extract possesses antinociceptive, anti-inflammatory and hypoglycaemic properties. The different flavonoids, polyphenols, triterpenoids and other chemical constituents of the herb are speculated to account for the observed antinociceptive, anti-inflammatory and antidiabetic properties of the plant.

Acetic Acid↗