Water extracts from Momordica charantia increase glucose uptake and adiponectin secretion in 3T3-L1 adipose cells

To examine the effects of Momordica charantia on glucose uptake and adiponectin secretion in adipose cells, 3T3-L1 adipocytes were treated with three concentrations (0.2, 0.3 and 0.4mg/ml) of water and ethanol extracts of Momordica charantia fruit and seeds alone and in combination with either 0.5nM or 50nM insulin. The treatment combination of 0.2mg/ml water extract and 0.5nM insulin was associated with significant (p<0.05) increases in glucose uptake (61%) and adiponectin secretion (75%) over control levels. The ethanol extract was not associated with an increase in glucose uptake; however, a dose-dependent decrease in basal glucose uptake and insulin-mediated glucose uptake was observed with the ethanol extract in combination with 50nM insulin. In the absence of insulin, no effects on glucose uptake were observed in adipocytes exposed to the water extracts whereas the highest concentration (0.4mg/ml) of the ethanol extract was associated with a significant (p<0.05) decrease in glucose uptake relative to controls. The present results indicate that water-soluble component(s) in Momordica charantia enhance the glucose uptake at sub-optimal concentrations of insulin in 3T3-L1 adipocytes, which is accompanied by and may be a result of increased adiponectin secretion from the 3T3-L1 adipocytes.     

Effects of Orthosiphon stamineus aqueous extract on plasma glucose concentration and lipid profile in normal and streptozotocin-induced diabetic rats

The objective of this study was to investigate the effects of Orthosiphon stamineus Benth. aqueous extract on plasma glucose concentration and lipid profile in normal and streptozotocin-induced diabetic rats. The chemical screening of the extract showed phenolic compound and flavonoid content were 13.24+/-0.33 mg/g and 1.73+/-0.14 microg/g, respectively. In oral glucose tolerance test, the extract (0.2-1.0 g/kg) significantly decreased plasma glucose concentration in a dose-dependent manner in both normal and diabetic rats. The extract at 1.0 g/kg was most effective in decreasing plasma glucose concentrations and the response was closed to the result of glibenclamide (5 mg/kg). After repeated daily oral administrations of the extract (0.5 g/kg) for 14 days, the extract significantly reduced plasma glucose concentration in diabetic rats at days 7 and 14. By the end of the study, plasma triglyceride concentration was lower in the extract-treated diabetic rats than untreated ones. Furthermore, plasma HDL-cholesterol concentration was significantly increased in diabetic rats treated with the extract. In perfused rat pancreas, the extract did not increase insulin secretion in the presence of 5.5 mM glucose, but 100 microg/ml extract potentiated glucose-induced insulin secretion. Our findings suggested that Orthosiphon stamineus aqueous extract is effective for alleviating hyperglycemia and improving lipid profile in diabetic rats.     

Hypoglycaemic effect of Teucrium polium: studies with rat pancreatic islets

The aquous extract of Teucrium polium (Labiatae) has long being used in Iran as a hypoglycaemic aid without any knowledge about its probable side effects and mode of action. In an effort to assess the claimed hypoglycaemic property of the crude drug and to get some knowledge about the mechanism of action, the crude extract (0.5 g plant powder per kg body weight) was administered orally to a group of streptozotocin diabetic rats for six consecutive weeks. A significant decrease (64%) in blood glucose concentration was observed in the treated animals compared to the untreated diabetic rats, without any measurable effects on the major biochemical factors. In addition, the crude extract significantly enhanced the blood insulin level by almost 160% compared to the untreated diabetic rats. The insulinotropic property of the Teucrium polium extract was further assessed by an in vitro investigation using isolated pancreatic rat islets. Our data indicated that Teucrium polium crude extract is able to enhance insulin secretion by almost 135% after a single dose of plant extract (equivalent to 0.1 mg plant leaf powder per mL of the culture medium) at high glucose concentration (16 mmol/L). Meanwhile, the time pattern of insulin secretion was not affected by the plant extract compared to the untreated islets. These data clearly show that the plant extract, probably without metabolic transformation, is able to reduce high blood glucose levels through enhancing insulin secretion by the pancreas.     

Antidiabetic Properties and Mechanism of Action of Orthosiphon stamineus Benth Bioactive Sub-fraction in Streptozotocin-induced Diabetic Rats

Orthosiphon stamineus is a popular folk medicine widely used to treat many diseases including diabetes. Previous studies have shown that the sub-fraction of chloroform extract was able to inhibit the rise of blood glucose levels in a glucose tolerance test. This study was carried out to evaluate the chronic effect and possible mechanism of action of the bioactive chloroform sub-fraction of O. stamineus using streptozotocin-induced diabetic rats and in vitro methods. Administration of the chloroform extract sub-fraction 2 (C?2-b) at a dose of 1 g/kg twice daily on diabetic rats for 14 days showed a significant lowering (p < 0.05) of the final blood glucose level compared to the pretreatment level. However, there were no significant differences in the plasma insulin levels post-treatment compared to the pretreatment levels for all doses of C?2-b. Conversely, C?2-b at a concentration of 2 mg/mL significantly increased (p < 0.001) the glucose uptake by the rat diaphragm muscle. The increase in glucose uptake was also shown when the muscle was incubated in a solution containing 1 IU/mL of insulin or 1 mg/mL of metformin. Furthermore, the effect of this sub-fraction on glucose absorption in the everted rat jejunum showed that C?2-b at concentrations of 0.5 mg/mL, 1 mg/mL and, 2 mg/mL significantly reduced the glucose absorption of the jejunum (p < 0.05–0.001). Similarly, the absorption of glucose was also inhibited by 1 mg/mL and 2 mg/mL of metformin (p < 0.001). These results suggest that the effect of C?2-b may be due to extra-pancreatic mechanisms. There was no evidence that the plant extract stimulated the release of insulin in order to lower the blood glucose level.     

The hypoglycaemic and antihyperglycaemic effect of citrullus colocynthis fruit aqueous extract in normal and alloxan diabetic rabbits

Effects of the aqueous, glycosidic, alkaloidal and saponin extracts of the rind of Citrullus colocynthis on the plasma glucose levels were investigated in normal rabbits, while the effects of saponin extract on the fasting plasma glucose levels were studied in alloxan induced diabetic rabbits. In normal rabbits, oral administration of aqueous extract (300 mg/kg) produced significant reduction in plasma glucose after 1 h and highly significant after 2,3 and 6 h. Phytochemical screening revealed that the rind of C. colocynthis and its aqueous extract contains tertiary and quaternary alkaloids, glycoside and saponin components. The hypoglycaemic effects of these components given orally at a dose (50 mg/kg) were studied in normoglycaemic rabbits. Result showed that the alkaloidal extract did not significantly lower the blood glucose levels from 132 mg/100 ml at 0 h to 120 mg/100 ml after 6 h, while the glycosidic extract significantly lowered the fasting glucose levels after 2 and 3 h and highly significant after 6 h. The effect was more pronounced with saponin extract, the saponin significantly lowered the fasting glucose levels after 1 and 2 h and highly significant (P<0.001) after 3 and 6 h. Graded doses (10, 15 and 20 mg/kg) of saponin extract, when given orally to alloxan diabetic rabbits, produced a significant reduction of plasma glucose concentration. These results suggest that the aqueous extract of the rind of C. colocynthis possesses a hypoglycaemic effect and its hypoglycaemic action could be attributed for more extent to the presence of saponin in addition to the presence of glycosidic components.     

Antihyperglycemic and insulin secretory activity of Costus pictus leaf extract in streptozotocin induced diabetic rats and in in vitro pancreatic islet culture

Aim of the study

The leaves of Costus pictus D. Don were used extensively for its antihyperglycemic activity by the people in Kerala, India. In the present study, the antihyperglycemic and insulin secretory activity of an aqueous extract of Costus pictus leaf extract was investigated in streptozotocin induced diabetic rats.

Materials and methods

Oral Glucose Tolerance Test was done to determine the effective dose of Costus pictus extract. Aqueous extract of Costus pictus leaves was given orally to the diabetic rats for 14 days. The insulin secretory action of the leaf extract was investigated using isolated pancreatic islets from rat. Liver glucose uptake activity was measured using d-[¹⁴C] glucose.

Results

The oral administration of an aqueous extract of Costus pictus at a dose of 250 mg/kg body weight significantly decreased the blood glucose with significant increase in plasma insulin level in diabetic rats at the end of 14 days treatment. The Costus pictus leaf extract significantly increased glucose induced insulin secretion at both 4 mM and 20 mM glucose concentrations which represents normal physiological and diabetic condition respectively. The decreased glucose uptake activity of the liver of diabetic rats was reverted to near normal levels after the treatment with Costus pictus leaf extract.

Conclusion

Our results suggest the glucose lowering effect of Costus pictus to be associated with the potentiation of insulin release from pancreatic islets and enhancement of peripheral utilization of glucose.     

Mulberry leaf extract stimulates glucose uptake and GLUT4 translocation in rat adipocytes

Mulberry (Morus alba L.) leaf tea is promoted for its health benefits and the control of diabetes in Asian nations. The blood glucose lowering activity of mulberry leaf extract (MA) has been proven; however, the molecular basis underlying this effect remains unclear. The aim of the present work is to elucidate its mechanism of the antihyperglycemic action, by examining the effect of MA on glucose uptake and the translocation of glucose transporter 4 protein (GLUT4) to the plasma membrane of adipocytes isolated from diabetic rats. The incubation of adipocytes with 5-45 μg/ml MA resulted in 31-54% increase of glucose uptake in a dose-dependent manner. This glucose uptake enhancing effect was inhibited by the phosphoinositol 3-kinase (PI3-K) inhibitor, wortmannin (100 nM). The GLUT4 protein on the plasma membrane fraction of adipocytes was markedly increased after treatment with 15 μg/ml MA extract. Interestingly, gallic acid, one of the phenolic compounds found in MA extract, increased glucose uptake and enhanced the translocation of GLUT4 at concentrations comparable to the amount of gallic acid in the effective concentration ranges of MA. Thus, it is likely that gallic acid contributes, at least in part, to its antihyperglycemic activity. The present results suggest that the antihyperglycemic action of MA is mediated by increasing glucose uptake via the activation of PI3-K signaling pathway and translocation of GLUT4 to the plasma membrane. These findings are the first molecular evidence supporting the mulberry tea as herbal medicine for diabetic patients.     

Effect of Cassia auriculata Linn. on serum glucose level,glucose utilization by isolated rat hemidiaphragm

An aqueous leaf extract of Cassia auriculata (C. auriculata) was found to lower the serum glucose level in normal rats. Maximum reduction in serum glucose level was observed after 4 h at a dose levels of 100, 200, 400 mg/kg body weight of the extract. In normal rats the serum glucose level reduction at 4th h was 23% by 100 mg/kg body weight and 31% by 200 mg/kg body weight. In alloxan-induced diabetic rats, chronic administration of the extract significantly reduced the serum glucose level from third day to till the end of the experiment. The extract was also found to inhibit the body weight reduction induced by alloxan administration. Glucose uptake and glycogen deposition studies suggest that C. auriculata leaf extract probably has no direct insulin like effect which can enhance the peripheral utilization of glucose.     

Ibervillea sonorae (Cucurbitaceae) induces the glucose uptake in human adipocytes by activating a PI3K-independent pathway

Ethnopharmacological relevance

Ibervillea sonorae (S. Watson) Greene (Cucurbitaceae), a plant used for the empirical treatment of type 2 diabetes in México, exerts antidiabetic effects on animal models but its mechanism of action remains unknown. The aim of this study is to investigate the antidiabetic mechanism of an Ibervillea sonorae aqueous extract (ISE).

Materials and methods

Non-toxic ISE concentrations were assayed on the glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes, both in the absence or the presence of insulin signaling pathway inhibitors, and on murine and human adipogenesis. Chemical composition of ISE was examined by spectrophotometric and HPLC techniques.

Results

ISE stimulated the 2-NBDGlucose uptake by mature adipocytes in a concentration-dependent manner. ISE 50 µg/ml induced the 2-NBDG uptake in insulin-sensitive 3T3-F442A, 3T3-L1 and human adipocytes by 100%, 63% and 33%, compared to insulin control. Inhibitors for the insulin receptor, PI3K, AKT and GLUT4 blocked the 2-NBDG uptake in murine cells, but human adipocytes were insensitive to the PI3K inhibitor Wortmannin. ISE 50 µg/ml also stimulated the 2-NBDG uptake in insulin-resistant adipocytes by 117% (3T3-F442A), 83% (3T3-L1) and 48% (human). ISE induced 3T3-F442A adipogenesis but lacked proadipogenic effects on 3T3-L1 and human preadipocytes. Chemical analyses showed the presence of phenolics in ISE, mainly an appreciable concentration of gallic acid.

Conclusion

Ibervillea sonorae exerts its antidiabetic properties by means of hydrosoluble compounds stimulating the glucose uptake in human preadipocytes by a PI3K-independant pathway and without proadipogenic effects.     

Effect of Trigonella foenum graceum on blood glucose levels in normal and alloxan-diabetic mice

The hypoglycemic effects of a decoction and an ethanol extract of Trigenolla foenum graceum seeds on the serum glucose levels of normal and alloxan diabetic mice were studied. A single 0.5 ml oral dose of 40-80% decoctions to normal as well as alloxanized mice was followed by hypoglycemia developed over a 6-h period. Reduction in blood glucose concentration was highly significant, was maximum at 6 h and was dose-dependent. The hypoglycemia caused by the ethanol extract (200-400 mg/kg) in alloxanized mice was also dose-dependent and 200 mg/kg was comparable in effect to 200 mg/kg tolbutamide.     

Anti-diabetic effect of cinnamon extract on blood glucose in db/db mice

The anti-diabetic effect of Cinnamomi cassiae extract (Cinnamon bark: Lauraceae) in a type II diabetic animal model (C57BIKsj db/db) was studied. Cinnamon extract was administered at different dosages (50, 100, 150 and 200 mg/kg) for 6 weeks. It was found that blood glucose concentration is significantly decreased in a dose-dependent manner (P<0.001) with the most in the 200 mg/kg group compared with the control. In addition, serum insulin levels and HDL-cholesterol levels were significantly higher (P<0.01) and the concentration of triglyceride, total cholesterol and intestinal alpha-glycosidase activity were significantly lower after 6 weeks of the administration. These results suggest that cinnamon extract has a regulatory role in blood glucose level and lipids and it may also exert a blood glucose-suppressing effect by improving insulin sensitivity or slowing absorption of carbohydrates in the small intestine.     

Insulinomimetic effect of kaempferol 3-neohesperidoside on the rat soleus muscle

A stimulatory effect of kaempferol 3-neohesperidoside ( 1) on glucose uptake (35% and 21%) was observed when the rat soleus muscle was incubated with 1 and 100 nM of this flavonoid glycoside, respectively. The concentration-response curve of insulin showed a stimulatory effect at 3.5 and 7.0 nM (42% and 50%) on glucose uptake when compared with the control group. The effect of 1 on glucose uptake was completely nullified by pretreatment with LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), and RO318220, an inhibitor of protein kinase C (PKC). However, no significant change occurred on glucose uptake stimulated by 1 when muscles were pretreated with PD98059, an inhibitor of mitogen-activated protein kinase (MEK), and cycloheximide, an inhibitor of protein synthesis. Compound 1 and insulin (7 nM) did not show a synergistic effect on glucose uptake. Additionally, 100 mg/kg of 1 by oral gavage was able to increase glycogen content in the muscle. These results suggest that 1 stimulates glucose uptake in the rat soleus muscle via the PI3K and PKC pathways and, at least in part, independently of MEK pathways and the synthesis of new glucose transporters.     

Effect of crude extract and fractions from Vitex megapotamica leaves on hyperglycemia in alloxan-diabetic rats

The effect of the crude extract, ethyl acetate and n-butanol fractions from Vitex megapotamica (Spreng) Moldenke on glycemia was investigated in diabetic rats. Oral administration of crude extract significantly reduced serum glucose levels in both normal and diabetic animals. In normal rats, serum glucose lowering was observed with 400 and 800 mg/kg at 2 and 2-3h, respectively after oral crude extract treatment. Nevertheless, the hypoglycemic effect of Vitex megapotamica in diabetic rats was evident at 1 and 2h and from 1 to 3h after treatment with 400 and 800 mg/kg, respectively. The ethyl acetate as well as n-butanol fractions were able to diminish glycemia in diabetic animals. The ethyl acetate fraction (400 and 800 mg/kg) produced the maximum hypoglycemic effect (28 and 20%, respectively) in diabetic rats and the same dose of the n-butanol fraction reduced the hyperglycemia only by 11% at 1h after treatment. Additionally, in hyperglycemic normal rats neither crude extract nor ethyl acetate fraction modified the glucose tolerance and the known tolbutamide effect on insulin release was clearly observed in this group. Thus, this study shows that Vitex megapotamica has an anti-hyperglycemic action, is able to ameliorate the diabetic state and, probably, is a source of hypoglycemic compounds.     

Korean red ginseng stimulates insulin release from isolated rat pancreatic islets

Ethnopharmacological relevance

Korean red ginseng (KRG), one of heat-processed Korean ginseng (Panax ginseng C.A. Meyer), has a long history as herbal remedy for antidiabetic effect.

Aim of the study

The effect and mechanism of KRG on stimulation of insulin release were investigated in isolated rat pancreatic islets.

Material and methods

Pancreatic islets isolated from rats were used to evaluate the insulinotropic action of KRG. The effect of Ca on the insulinotropic action of KRG was investigated.

Results

The aqueous ethanolic extract of KRG (AEE-KRG) (0.1–1.0 mg/ml) significantly evoked a stimulation of insulin release at 3.3 mM glucose compared to the control. Experiments at different glucose concentrations (8.4 and 16.7 mM) showed that AEE-KRG significantly stimulated on its own whereas it did not potentiate insulin secretion induced by glucose. The extracellular Ca²⁺-free condition, a L-type Ca²⁺ channel blocker and an ATP-sensitive K⁺ channel opener significantly inhibited insulin secretion evoked by AEE-KRG.

Conclusion

These findings suggest that KRG displays beneficial effects in the treatment of diabetes at least in part via the stimulation of insulin release in a glucose-independent manner.     

Effect of a polyphenol-rich extract from Aloe vera gel on experimentally induced insulin resistance in mice

Insulin resistance, which precedes type 2 diabetes mellitus (T2DM), is a widespread pathology associated with the metabolic syndrome, myocardial ischemia, and hypertension. Finding an adequate treatment for this pathology is an important goal in medicine. The purpose of the present research was to investigate the effect of an extract from Aloe vera gel containing a high concentration of polyphenols on experimentally induced insulin resistance in mice. A polyphenol-rich Aloe vera extract (350 mg/kg) with known concentrations of aloin (181.7 mg/g) and aloe-emodin (3.6 mg/g) was administered orally for a period of 4 weeks to insulin resistant ICR mice. Pioglitazone (50 mg/kg) and bi-distilled water were used as positive and negative controls respectively. Body weight, food intake, and plasma concentrations of insulin and glucose were measured and insulin tolerance tests were performed. The insulin resistance value was calculated using the homeostasis model assessment for insulin resistance (HOMA-IR) formula. Results showed that the polyphenol-rich extract from Aloe vera was able to decrease significantly both body weight (p < 0.008) and blood glucose levels (p < 0.005) and to protect animals against unfavorable results on HOMA-IR, which was observed in the negative control group. The highest glucose levels during the insulin tolerance curve test were in the negative control group when compared to the Aloe vera extract and pioglitazone treated mice (p < 0.05). In conclusion, Aloe vera gel could be effective for the control of insulin resistance.     

Peroxisome proliferator-activated receptor gamma transactivation-mediated potentiation of glucose uptake by Bai-Hu-Tang

ETHNOPHARMACOLOGICAL RELEVANCE: The molecular mechanism of a traditional hypoglycemic Chinese herbal formula. AIM OF THE STUDY: To explore the glucose uptake effect as well as the mechanism(s) of action of Bai-Hu-Tang (BHT), a traditional Chinese herbal formula, composed of anemarrhena, gypsum, licorice and rice. MATERIALS AND METHODS: Differentiated 3T3-L1 adipocytes were treated with vehicle, insulin or insulin plus different concentrations of BHT. The 2-deoxy-[(3)H] glucose uptake assay was performed to measure the amount of glucose uptake. To explore the mechanism(s) of glucose uptake of BHT, we used two insulin signaling transduction inhibitors, N-Acetyl-Leu-Leu-Norleu-al (ALLN), a calpain inhibitor, and LY 294002, a phosphatidylinositol (PI)3-kinase inhibitor, to test if the glucose uptake effect was mediated by the insulin signaling pathway. We then used Western blot analysis to re-confirm the result of the insulin signaling inhibition assay. Finally, reporter chimera assay of HuH-7 cells was used to measure the peroxisome proliferator-activated receptor gamma (PPARgamma) activation by BHT. RESULTS: BHT potentiated insulin-stimulated glucose uptake in 3T3-L1 adipocytes. The effect of BHT-stimulated glucose uptake was neither inhibited by ALLN nor by LY 294002. The protein expression of PI3 kinase pathway did not change after BHT stimulation. PPARgamma activation was elevated by 67.7+/-32% (p<0.05) in HuH-7 cells treated with 0.8 microg/ml of BHT. CONCLUSIONS: BHT stimulated glucose uptake in 3T3-L1 adipocytes. This effect was via PPARgamma activation rather than via the insulin signaling pathway.     

The insulinotropic activity of a Nepalese medicinal plant Biophytum sensitivum: preliminary experimental study

The effect of the leaf extract of Biophytum sensitivum, an annual herb used in traditional Nepalese folk medicine for the treatment of hyperglycemic patients, was studied on glucose homeostasis in rabbits. In the first set of experiments, an acute effect of the extract on fasting plasma glucose (fpg) levels and serum insulin response was examined in non-diabetic and alloxan-diabetic rabbits. Initial dose-response studies showed that a dose of 200 mg/kg body weight (b.w.) was optimum for hypoglycemia. A single administration of this dose to 16-h fasted non-diabetic rabbits brought about a 16.1% fall in fpg at the end of 1 and 2 h, and the hypoglycemic effect persisted at the end of 6 h (13.8% fall). Serum insulin levels showed a significant rise in the treated animals, which suggested a pancreatic mode of action (i.e. insulinotropic effect) of B. sensitivum. The study of an acute effect of the extract in alloxan-diabetic rabbits, however, showed that it failed to produce such hypoglycemic or serum insulin response. In another set of experiments, administration of the above dose of the leaf extract attenuated the plasma glucose response to oral administration of 3 g/kg b.w. glucose load. The serum insulin levels in the treated animals showed a rise at the end of 2 (13.7% rise) and 6 h (12.6% rise). Taken together, these observations suggest that the hypoglycemic response of B. sensitivum may be mediated through stimulating the synthesis/release of insulin from the beta cells of Langerhans.     

Comparative evaluation of two different Opuntia ficus‐indica extracts for blood sugar lowering effects in rats

Stems of Opuntia ficus‐indica (L.) Mill. (OFI) are traditionally used in Mexico to treat diabetes mellitus. Less research data are available for combinations of stem and fruit preparations. The present study was designed to investigate the effects of an aqueous extract prepared from the cladodes and a proprietary stem/fruit skin‐blend (stem/fruit skin ratio 75/25) of OFI on blood glucose and plasma insulin in normal rats. A dose finding study with the traditional cladode OFI extract revealed that maximum effects on blood glucose and insulin were observed after oral administration in a dose range of 6–176 mg/kg. The proprietary OFI blend significantly lowered blood glucose levels in the glucose tolerance test to a similar extent (p < 0.05 vs control) as the traditional aqueous cladode extract when administered in a dose of 6 mg/kg. In contrast to the aqueous extract, the proprietary blend significantly increased basal plasma insulin levels (p < 0.01 vs control) indicating a direct action on pancreatic beta cells. The results suggest that both OFI extracts exert hypoglycemic activities in rats in doses as low as 6 mg/kg but that the effects of the proprietary stem/fruit blend were more pronounced in our model. Copyright © 2010 John Wiley & Sons, Ltd.     

Induction of insulin secretion by an aqueous extract of Tabernanhte iboga Baill. (Apocynaceae) in rat pancreatic islets of Langerhans

The effect of an aqueous extract of Tabernanthe iboga (TBEt) was studied in the rat islets insulin secretion based on its use in traditional medicine for the treatment of diabetes. Rats islets were isolated by collagenase digestion. In insulin release experiments, the insulin content was determined by Enzyme-Link Immunosorbent Assay (ELISA). For experiments on ⁴⁵Ca²⁺ Uptake, the radioactive content was determined using a liquid scintillation analyzer. The extract (10⁻³ μg/ml-100 μg/ml) did not exert a significant increase of insulin secretion (p > 0.05) in the presence of 2.8 mM of glucose (a none stimulatory concentration). Whereas, in the presence of 11.1 mM of glucose (stimulatory concentration), TBEt augmented glucose-stimulated insulin secretion in a dose-dependent manner. Interestingly, the secretory effect of the extract was glucose-dependent (5.6-16.7 mM). Furthermore, the insulinotropic effect of TBEt (1 μg/ml) was significantly potentiated (p < 0.001) in K⁺-depolarised media as well as in the presence of 2.8 mM and 16.8 mM of glucose concentrations. In contrast, in the same conditions, TBEt failed to stimulate the high K⁺ medium-induced insulin release. The extract significantly amplified (p < 0.001 and p < 0.05) the insulin secretion induced by either IBMX or tolbutamide. Diazoxide, cobalt or calcium removal inhibited the insulinotropic effect of the extract. TBEt increased glucose-induced ⁴⁵Ca²⁺ uptake in rat islets. Overall, our findings suggest that Tabernanthe iboga contains water soluble insulinotropic compounds. The insulin secretion of TBEt's active principles might involve the closure of K⁺-ATP and the intensification of calcium influx through voltage-sensitive Ca²⁺ channels.