Protective effects of Ficus carica leaves on glucose and lipids levels,carbohydrate metabolism enzymes and β-cells in type 2 diabetic rats

Context: The decoctions of Ficus carica Linn. (Moraceae) leaves are used in the folklore treatment of diabetes.

Objective: To evaluate the effect of F. carica on glucose and lipids levels, carbohydrate metabolism enzymes and β-cells protective effects in type 2 diabetes.

Material and methods: Diabetes was induced in 15 days high-fat diet (HFD)-fed Wistar rats by intraperitoneal injection of streptozotocin (STZ) (40?mg/kg). The ethyl acetate extract (250 and 500?mg/kg) of F. carica leaves was administered for 28 days. Oral glucose tolerance (OGTT) and intraperitoneal insulin tolerance tests (ITT) were evaluated on 15th and 25th days, respectively.

Results: The ethyl acetate extract (250 and 500?mg/kg) of n F. carica leaves showed significant effect (p?F. carica (250 and 500?mg/kg) significantly (p?F. carica enhanced the glucose utilization significantly (p?<?0.005) over 30 and 60?min compared to diabetic control. Further, the altered activities of key carbohydrate metabolizing enzymes such as glucose-6-phosphatase, fructose-1,6-bisphosphatase and hexokinase in the liver tissue of diabetic rats were significantly (p?F. carica. Immumohistochemical studies of islets substantiated the cytoprotective effect on pancreatic β-cells.

Discussion and conclusions: F. carica leaves exerted significant effect on carbohydrate metabolism enzymes with promising hypoglycemic and hypolipidemic activities in type 2 diabetic rats.     

Depression of glucose levels and partial restoration of pancreatic β-cell damage by melatonin in streptozotocin-induced diabetic rats

Diabetes mellitus is a common but serious metabolic disorder associated with many functional and structural complications. Glucose metabolism is disturbed due to an absolute or relative insulin deficiency. The experiment was carried out to determine the effect of melatonin on blood glucose and insulin concentrations, and histopathology of pancreatic β-cells in streptozotocin (STZ)-induced diabetic rats. The rats were randomly allocated into one of the four experimental groups: group A (control), group B (diabetic untreated), group C (diabetic treated with melatonin for 6 weeks) and group D (diabetic treated with melatonin for 8 weeks); each group contained ten animals. Diabetes was induced in B, C and D groups by a single intraperitoneal (i.p.) injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/l citrate buffer, pH 4.5). The rats in melatonin-treated groups were subjected to the daily i.p injection of 10 mg kg⁻¹ of melatonin for 6 or 8 weeks starting the day after STZ injection. Control and diabetic untreated rats were injected with the same volume of isotonic NaCl as the melatonin treated groups. Almost all insulin-positive β-cells were degranulated, degenerated or necrotic in the STZ-treated rats leading to decrease in insulin secretion and an increase in blood glucose concentration. Melatonin treatment caused a sharp decrease in the elevated serum glucose, a slight increase in the lowered serum insulin concentrations and small partial regeneration/proliferation of β-cells of islets. It is concluded that the hypoglycemic action of melatonin could be partly due to small amelioration in the β-cells of pancreatic islets causing a slight increase in insulin secretion, it is mostly due to the extrapancreatic actions of the melatonin.     

Beneficial effect of 17β-estradiol on hyperglycemia and islet β-cell functions in a streptozotocin-induced diabetic rat model

The modulating effect of estrogen on glucose homeostasis remains a controversial issue at present. In this study, we sought to determine the beneficial effect of 17β-estradiol (E₂) on hyperglycemia and islet β-cell functions in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were injected i.p. with STZ to induce a relatively mild diabetic condition. The rats were then treated with E₂ orally at 500 μg/kg body weight/day for 15 days to evaluate the modulating effect on hyperglycemia, insulin secretion, and islet β-cell proliferation. E₂ administration for 10 days significantly lowered plasma glucose levels, increased plasma insulin levels, and improved glucose tolerance by attenuating insulin response to oral glucose loading. These beneficial effects of E₂ were accompanied by increases in islet number and volume, rate of islet cell proliferation, and the amount of insulin secreted. The growth-stimulatory effect of E₂ on islet cells was linked to the functions of the estrogen receptor α. Notably, these protective effects of E₂ on diabetic conditions were basically not observed when the STZ-treated rats had a more severe degree of islet damage and hyperglycemia. Taken together, we conclude that E₂ can promote the regeneration of damaged pancreatic islets by stimulating β-cell proliferation in diabetic rats, and this effect is accompanied by improvements in glucose tolerance and a decrease in plasma glucose levels. These findings suggest that oral administration of E₂ may be beneficial in diabetic patients with an accelerated loss of islet β-cells.     

Ursolic acid enhances the cellular immune system and pancreatic β-cell function in streptozotocin-induced diabetic mice fed a high-fat diet

This study investigated the effects of ursolic acid on immunoregulation and pancreatic β-cell function in type 1 diabetes fed a high-fat diet for 4 weeks. Male mice were divided into non-diabetic, diabetic control, and diabetic-ursolic acid (0.05%, w/w) groups, which were fed a high-fat (37% calories from fat). Diabetes was induced by injection of streptozotocin (200 mg/kg B.W., i.p.). Ursolic acid significantly improved blood glucose levels, glucose intolerance, and insulin sensitivity compared to the diabetic group. The plasma insulin and C-peptide concentrations were significantly higher in the diabetic-ursolic acid group than in the diabetic group. Ursolic acid significantly elevated the insulin levels with preservation of insulin staining of β-cells in the pancreas. In splenocytes, concanavalin (Con) A-induced T-cell proliferation was significantly higher in the diabetic-ursolic acid group compared to the diabetic group, but liposaccharide (LPS)-induced B-cell proliferation did not differ between groups. Ursolic acid enhanced IL-2 and IFN-γ production in response to Con A stimulation, whereas it inhibited TNF-α production in response to LPS stimulation. In this study, neither streptozotocin nor ursolic acid had effects on lymphocyte subsets. These results indicate that ursolic acid exhibits potential anti-diabetic and immunomodulatory properties by increasing insulin levels with preservation of pancreatic β-cells and modulating blood glucose levels, T-cell proliferation and cytokines production by lymphocytes in type 1 diabetic mice fed a high-fat diet.     

Modulation of serum concentrations and hepatic metabolism of 17β-estradiol and testosterone by amitraz in rats

The present study has investigated the ability of amitraz, a widely used formamidine pesticide, to modulate serum concentrations and liver microsomal metabolism of 17β-estradiol (E2) and testosterone in rats. Amitraz was administered intraperitoneally to male rats for 4 days and to intact female rats or ovariectomized (OVX) and 0.5 mg/kg E2-supplemented female rats for 7 days. E2 and metabolites were analyzed by gas chromatography-electron capture detection and testosterone and metabolites were analyzed by high-pressure liquid chromatography. In OVX and E2-supplemented females, 50 mg/kg amitraz caused an 85% decrease of serum E2 concentration and a marked increase of 2-OH-E2 concentration. Amitraz at 25 and 50 mg/kg produced 9.0-fold or greater increases of serum testosterone and 2β-OH-testosterone levels in males. Amitraz at 25 mg/kg resulted in no or minimal increases of liver microsomal formation of E2 or testosterone metabolites. Amitraz at 50 mg/kg produced 1.4- to 3.6-fold increases of 2-OH-E2; estrone; 2β-, 6β-, and 16α-OH-testosterone; and androstenedione formation in males and intact females. Amitraz at 50 mg/kg preferentially increased intact female 16β-OH-testosterone production by 8.6-fold. In OVX females, E2 supplement alone or cotreatment with E2 and 50 mg/kg amitraz produced 1.3- to several-fold increases of 2- and 4-OH-E2 formation and 2β- and 16α-OH-testosterone production. The cotreatment increased 6β- and 16β-OH-testosterone formation by 1.8- and 1.6-fold, respectively. The present findings show that amitraz induces hepatic E2 and testosterone metabolism in male and female rats, decreases serum E2 concentration in OVX and E2-supplemented females, but increases serum testosterone in males.     

Hypoglycemic and β-cells regenerative effects of Aegle marmelos (L.) Corr. bark extract in streptozotocin-induced diabetic rats

The aim of this study was to examine the antidiabetic potential of Aegle marmelos (L.) Corr. (Rutaceae) bark in a diabetic rat model. Dose dependent effects of methanol extract of Aegle marmelos bark (AM) (200 and 400 mg/kg) on blood glucose, plasma insulin, glycated haemoglobin (HbA1c), total protein, hepatic glycogen, marker enzymes of hepatic function and carbohydrate metabolism were evaluated in (streptozotocin) STZ-induced diabetic rats by oral administration for 30 days. Structural integrity of pancreatic islets was assessed by routine histology while, their functional status was assessed by immunolocalization for insulin. High-performance liquid chromatography (HPLC) study established that AM contained antihyperglycemic constituents, aegelin (1.27% w/w) and lupeol (0.29% w/w). AM at 200 and 400 mg/kg showed significant reduction in blood glucose level by 19.14% and 47.32%, respectively in diabetic rats. AM treatment significantly increased insulin level, and produced similar effects on other biochemical parameters. Histological studies showed the regenerative effect of AM on the β-cells of diabetic rats. Immunohistochemical observations in the extract treated diabetic rats showed increased insulin-immunoreactive β-cells. These findings suggest that A. marmelos bark extract has the therapeutic potential in STZ-induced hyperglycemia; hence it can be used in the treatment of diabetes mellitus.     

In vivo recovery effect of silibinin treatment on streptozotocin-induced diabetic mice is associated with the modulations of sirt-1 expression and autophagy in pancreatic β-cell

Improper adjustments of autophagy and silent information regulator 1 (Sirt-1) expression were reported to be closely associated with metabolic disorders. In this study, we examined the roles of Sirt-1 and autophagy in streptozotocin-induced diabetes mellitus, assessed the relationship between autophagy and Sirt-1, and investigated the protective mechanism of silibinin. Diabetes was induced in 6-week-old mice by intravenous injection of streptozotocin (150 mg/kg/day, for 2 weeks). In the treatment groups, silibinin (50 mg/kg/day, intramuscular injection, for 8 weeks) or inhibitors (50 mg/kg/day, subcutaneous injection, for 8 weeks) were given. Diabetic control animals received vehicle for the same time. Compared with diabetic controls, silibinin or autophagy inhibitor, 3-methyladenine, treated mice showed decreased levels of glycosylated hemoglobin A1C (P < 0.01), serum triglyceride (P < 0.01), cholesterol (P < 0.01), blood glucose (P < 0.05), autophagy (P < 0.05), and apoptosis ratio (P < 0.05) of pancreatic β-cells. Systemic administration of silibinin reversed streptozotocin-induced downregulation of Sirt-1 expression. Sirt-1 may play a role in regulating the physiological level of autophagy and is associated with loss of pancreatic β-cells and metabolic biochemical disorders. Through promoting Sirt-1 expression and recovering autophagy physiologically, silibinin may reverse hyperglycemia and repair damaged pancreatic β-cells.     

In vivo recovery effect of silibinin treatment on streptozotocin-induced diabetic mice is associated with the modulations of Sirt-1 expression and autophagy in pancreatic β-cell

Improper adjustments of autophagy and silent information regulator 1 (Sirt-1) expression were reported to be closely associated with metabolic disorders. In this study, we examined the roles of Sirt-1 and autophagy in streptozotocin-induced diabetes mellitus, assessed the relationship between autophagy and Sirt-1, and investigated the protective mechanism of silibinin. Diabetes was induced in 6-week-old mice by intravenous injection of streptozotocin (150?mg/kg/day, for 2 weeks). In the treatment groups, silibinin (50?mg/kg/day, intramuscular injection, for 8 weeks) or inhibitors (50?mg/kg/day, subcutaneous injection, for 8 weeks) were given. Diabetic control animals received vehicle for the same time. Compared with diabetic controls, silibinin or autophagy inhibitor, 3-methyladenine, treated mice showed decreased levels of glycosylated hemoglobin A1C (P?相似文献   

Inhibition of PKC-θ preserves cardiac function and reduces fibrosis in streptozotocin-induced diabetic cardiomyopathy

Background and Purpose

T-cell infiltration, interstitial fibrosis and cardiac dysfunction have been observed in diabetic patients with cardiovascular diseases. PKC-θ is crucial for the activation of mature T-cells. We hypothesized that inhibition of PKC-θ might protect diabetic hearts through inhibition of T-cell stimulation and maintenance of tight junction integrity.

Experimental Approach

A model of type 1 diabetes was induced by streptozotocin (STZ) (50 mg kg^–1 for 5 days) in male C57BL/6J wild-type (WT) mice and Rag1 knockout (KO) mice which lack mature lymphocytes. A cell-permeable selective PKC-θ peptide inhibitor (PI) was administered i.p. (0.2 mg kg^–1·day^–1) for 4 weeks (first phase) and 2 weeks (second phase). At the end of the 11th week, cardiac contractile force was measured in isolated perfused hearts. Cardiac morphology and fibrosis were determined. Phosphorylation of PKC-θ at Tyr³⁵⁸, infiltrated T-cells and tight junction protein ZO-1 within the hearts were detected, using immunohistochemcial techniques.

Key Results

PI did not affect high blood glucose level in both WT and Rag1 KO diabetic mice. Diabetes induced cardiac fibrosis in WT mice but not in Rag1 KO mice. PI attenuated cardiac fibrosis and improved cardiac contractility of WT diabetic hearts. PI decreased expression of phosphorylated PKC-θ, reduced the infiltration of T-cells and increased ZO-1 expression within WT diabetic hearts.

Conclusion and Implications

Inhibition of PKC-θ improves cardiac function and reduces cardiac fibrosis in WT mice with streptozotocin-induced diabetes. Mature T-cells play a key role in pathophysiology of diabetic cardiomyopathy.     

Metabolism of β-myrcene in vivo and in vitro: its effects on rat-liver microsomal enzymes

Abstract

1. Metabolites isolated from the urine of rats after oral administration of β-myrcene (I) were: 10-hydroxylinalool (II), 7-methyl-3-methylene-oct-6-ene-1,2-diol (IV), 1-hydroxymethyl-4-isopropenyl cyclohexanol (VI), 10-carboxylinalool (III) and 2-hydroxy-7-methyl-3-methylene-oct-6-enoic acid (V).

2. Liver microsomes prepared from phenobarbital-treated rats convert β-myrcene (I) to 10-hydroxylinalool (II) in the presence of NADPH and oxygen. NADH neither supported this reaction nor did it show any synergistic effect. The rate of conversion was significantly greater in microsomes prepared from phenobarbital-treated rats than from 3-methylcholanthrene-treated or control microsomal preparations. The formation of 10-hydroxylinalool (II) was inhibited by metyrapone, carbon monoxide, SKF-525A, p-chloromercuric benzoate (p-CMB) and cytochrome c.

3. Titration of phenobarbital-induced liver microsomes with β-myrcene (I) produced a series of type I difference spectra with peaks around 387–390?nm and troughs around 421–425?nm. The K_s for β-myrcene was 10.6 μM.

4. Administration (four days) of β-myrcene (I) to rats did not result in any significant effect on the hepatic drug-metabolizing enzymes.     

Intravenous immunoglobulin improves glucose control and β-cell function in human IAPP transgenic mice by attenuating islet inflammation and reducing IAPP oligomers

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by β-cell loss, insulin resistance, islet inflammation and amyloid deposits derived from islet amyloid polypeptide (IAPP). Reducing toxic IAPP oligomers and inhibiting islet inflammation may provide therapeutic benefit in treating T2DM. Intravenous immunoglobulin (IVIg) is an efficient anti-inflammatory and immunomodulatory agent for the treatment of several autoimmune or inflammatory neurological diseases. However, whether IVIg has therapeutic potential on T2DM remains unclear. In present study, we showed that IVIg treatment significantly improved glucose control and insulin sensitivity, and prevented β-cell apoptosis by lowering toxic IAPP oligomer levels, attenuating islet inflammation and activating autophagy in human IAPP transgenic mouse model. These results suggest that IVIg is a promising therapeutic potential for T2DM treatment.     

Antagonism of the antidepressant-like effects of clenbuterol by central administration of β-adrenergic antagonists in rats

Rationale Stimulation of central ₂ adrenergic receptors produces antidepressant-like effects on behavior. At present, it is not known what brain sites are involved in mediating such effects, although some recent evidence suggests the importance of the dorsal hippocampus.Objective Experiments were carried out to determine whether central administration of -adrenergic antagonists blocks antidepressant-like effects produced by peripheral administration of the ₂-adrenergic agonist clenbuterol.Methods The following were determined: 1) the ability of ICV or intrahippocampal administration of the non-selective adrenergic antagonists propranolol and CGP-12177, which are lipophilic and hydrophilic, respectively, to antagonize the effects of peripherally administered clenbuterol on differential-reinforcement-of-low-rate (DRL) behavior; 2) the effects of clenbuterol, administered bilaterally into the dorsal hippocampus, on DRL behavior.Results The antidepressant-like effects of clenbuterol, i.e. reduced response rate and increased reinforcement rate under the DRL schedule, were antagonized by either ICV or bilateral intrahippocampal infusions of propranolol or CGP-12177; CGP-12177 was approximately 8-fold more potent than propranolol. Direct infusion of clenbuterol into the bilateral dorsal hippocampus also produced antidepressant-like effects.Conclusions Central -adrenergic receptors, in particular those in the dorsal hippocampus, are involved in the mediation of the antidepressant-like effect of clenbuterol. Probably resulting from its enhanced access to the sites of action, the hydrophilic antagonist CGP-12177 was more potent than the lipophilic antagonist propranolol, even though they exhibit similar potency in vitro.     

Kinetics of butyrate metabolism in the normal colon and in ulcerative colitis: the effects of substrate concentration and carnitine on the β-oxidation pathway

Aliment Pharmacol Ther 2011; 34: 526–532

Summary

Background Butyrate, a colonic metabolite of carbohydrates, is considered as the major energy source for the colonic mucosa. An impaired butyrate metabolism has been reported in ulcerative colitis (UC), however, the cause still remains unknown. Aim In the present study, we investigated whether higher butyrate concentrations could normalise the oxidation rate in UC. Furthermore, it was investigated whether carnitine could enhance the butyrate oxidation. Methods Mucosal biopsies from a total of 26 UC patients and 25 controls were incubated with ¹⁴C‐labelled Na‐butyrate and the produced ¹⁴CO₂ was measured. First, the rate of oxidative metabolism was compared at three different concentrations of Na‐butyrate (0.05 mm , 1 mm and 10 mm ). Then, incubations of biopsies were performed with carnitine alone or combined with ATP. Results Overall, butyrate oxidation in UC was significantly lower than that in controls. The maximum rate of butyrate oxidation was achieved in UC and control subjects from 1 mm onwards. Increasing the butyrate concentration to a level to be present in the colonic lumen, i.e. 10 mm , did not increase the rate of butyrate oxidation in UC to the rate observed in controls. Addition of carnitine alone or combined with ATP caused no effects. Conclusions Saturation of butyrate kinetics was achieved from 1 mm in UC and control subjects. The rate of butyrate metabolism was significantly impaired in active ulcerative colitis. The addition of compounds interfering with the β‐oxidation pathway had no effect on the butyrate metabolism in UC.     

Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin–cadmium induced diabetic nephrotoxic rats

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)–cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ–Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ–Cd induced diabetic nephrotoxic rats.     

Sulforaphane protects against cytokine- and streptozotocin-induced β-cell damage by suppressing the NF-κB pathway

Sulforaphane (SFN) is an indirect antioxidant that protects animal tissues from chemical or biological insults by stimulating the expression of several NF-E2-related factor-2 (Nrf2)-regulated phase 2 enzymes. Treatment of RINm5F insulinoma cells with SFN increases Nrf2 nuclear translocation and expression of phase 2 enzymes. In this study, we investigated whether the activation of Nrf2 by SFN treatment or ectopic overexpression of Nrf2 inhibited cytokine-induced β-cell damage. Treatment of RIN cells with IL-1β and IFN-γ induced β-cell damage through a NF-κB-dependent signaling pathway. Activation of Nrf2 by treatment with SFN and induction of Nrf2 overexpression by transfection with Nrf2 prevented cytokine toxicity. The mechanism by which Nrf2 activation inhibited NF-κB-dependent cell death signals appeared to involve the reduction of oxidative stress, as demonstrated by the inhibition of cytokine-induced H₂O₂ production. The protective effect of SFN was further demonstrated by the restoration of normal insulin secreting responses to glucose in cytokine-treated rat pancreatic islets. Furthermore, pretreatment with SFN blocked the development of type 1 diabetes in streptozotocin-treated mice.     

Does impairment of renal and hepatic function influence the metabolism of thrombolytics in patients with myocardial infarction?

Thrombolytic agents activate plasminogen and induce a systemic fibrinolytic and anticoagulant state. Two thrombolytic drugs are used frequently in practice: streptokinase (SK) and alteplase (t-PA). Streptokinase mainly undergoes renal elimination with a half-life of 11-17 min, while alteplase is eliminating by the liver with a half-life of 4-6 min. Our goal was to examine whether renal and hepatic function influence the elimination and metabolism of thrombolytics and the efficacy of percutaneous coronary intervention (PCI) after using alteplase or streptokinase. 416 patients with myocardial infarction (MI) were treated from January 2001 to December 2003 (228 male and 189 female). Alteplase was used in 9 men and 6 women (mean age: 53.88 +/- 9.61 vs. 65.33 +/- 9.87 years, p = 0.07). Patients who underwent rescue PCI after administration of alteplase had slightly higher hepatic enzyme levels/alanine transaminase (ALT): 47.85 vs. 41.4 U/l; gamma-glutamyl transpeptidase (GGT): 69.5 vs. 44.8 U/l/. All patients treated with alteplase survived, rescue PCI was done in 8 cases. Streptokinase was used in 36 men and 28 women (mean age: 63.33 +/- 10.51 vs. 63 +/- 12.03 years, p = 0.9). We did not find a difference between serum creatinine levels of patients who received streptokinase and underwent PCI as compared to those who had not. Rescue PCI was done in 16 cases. 12 patients died in this group. In conclusion we have not found a significant correlation between the use of the thrombolytics and hepatic or renal function; this could indicate that such a slight impairment of liver and renal function does not influence pharmacokinetic properties of thrombolytics.     

Protective effects of icariin on learning and memory deficits induced by aluminium in rats

This study examined the protective effects of icariin （ICA） on the learning and memory deficits in Aluminium （Al） -treated rats and potential mechanisms. The screened, qualified rats were treated with 1. 6 g/L AlCl3 in drinking water for 8 months, and the ability of spatial learning and memory was tested by Morris water maze. Aluminium （Al） administration significantly increased the mean escape latency searching distance in place navigation test, and decreased the searching time in the quadrant once the platform was in space probe test and adjusted searching distance in space probe test, indicative of brain spatial learning and memory deficits. ICA treatment （60, 120 mg/kg, i. g 3 month） significantly protected against Al-induced spatial learning and memory deficits, as evidenced by decreased escape latency and searching distance, and by increased the searching time in the quadrant once the platform was adjusted via searching distance compared with the Al alone group. To examine the mechanisms of the protection, the activities of superoxide dismuase （SOD） and the contents of maloidaldehyde （MDA） in hippocampus were assayed by commercial kits, and the level of Aβ1-40 in hippocampus was examined by immunohistochemistry （IHC）, respectively. ICA treatment significantly increased the activities of SOD, decreased the content of MDA and the level of Aβ1-40 in hippocampus in a dose - dependent manner. In summary, this study demonstrates that ICA is effective in improving the ability of spatial learning and memory of Al-intoxicated rats.     

The effects of glyburide and insulin on the decreased β-adrenergic responsiveness of the gastrointestinal tract in rats with non-insulin-dependent diabetes

• 1.1. Decreased β-adrenergic responses have been reported in gastro-intestinal tract of rats with diabetes mellitus. Effects of glyburide and insulin on the decreased β-adrenergic responsiveness of the gastro-intestinal tract due to non-insulin-dependent diabetes were investigated using duodenum, jejunum and ileum from rats which were injected with alloxan in their neonatal periods.
• 2.2. Insulin treatment of non-insulin-dependent diabetic rats for 10 days corrected the decreased β-adrenergic responses of the isolated duodenum, jejunum and ileum confirming the previous results obtained from insulin-dependent diabetic rats.
• 3.3. Glyburide treatment alone for 3 weeks also reversed the changes in the gastro-intestinal β-adrenergic responses of non-insulin-dependent diabetic rats. Combination of glyburide with insulin, however, did not cause an additive or supra-additive interaction in terms of β-adrenergic sensitivities of the diabetic tissues.
• 4.4. The results obtained in the present study strongly suggested that non-insulin-dependent diabetes may cause a decrease in the number of gastro-intestinal β-adrenoceptors, while glyburide and insulin treatments correct the changes related to β-adrenoceptors. The effect of insulin on the β-adrenergic sensitivity of diabetic rat duodenum, jejunum and ileum may occur via a direct mechanism, whereas glyburide seems to be effective on the β-adrenergic responses through the increases in the insulin secretion and/or in the number of gastro-intestinal insulin receptors.