Hypoglycaemic activity of Bauhinia holophylla through GSK3-ß inhibition and glycogenesis activation.

CONTEXT: Bauhinia L. species, including Bauhinia holophylla (Bong.) Steud. (Fabaceae), have traditionally been used to treat diabetes. Bauhinia is a complex botanical genus, and the indiscriminate use of the diverse Bauhinia species is reflected in the experimental divergence of their medicinal potential. OBJECTIVE: The hypoglycaemic and hypolipidaemic effects, molecular mechanism of action and phytochemical properties of an authentic extract of B. holophylla leaves were evaluated. MATERIALS AND METHODS: A phytochemical study of a 70% EtOH extract was performed using FIA-ESI-IT-MS/MSn and HPLC-PAD-ESI-IT-MS. The extract (200 or 400 mg/kg b.w.) was administered for 14 days to streptozotocin-induced diabetic Swiss mice. Glucose tolerance and insulin sensitivity, blood parameters, gene and protein expression, and the in vivo and in vitro inhibition of intestinal glucosidases were assessed. RESULTS: HPLC-PAD-ESI-IT-MS analysis identified flavonoid derivatives of quercetin, myricetin, luteolin and kaempferol. Treatment with 400 mg/kg of the extract reduced blood glucose (269.0 ± 32.4 mg/dL vs. 468.0 ± 32.2 mg/dL for diabetic animals), improved glucose tolerance, decreased cholesterol and triglyceride levels, and increased the mRNA expression of proteins involved in glucogenesis in the liver and muscle, such as PI3-K/Akt, GS, GSK3-ß (ser-9), AMPK and Glut4. The activity of intestinal maltase was inhibited in vitro (IC50: 43.0 µg/mL for the extract compared to 516.4 µg/mL for acarbose) and in vivo. DISCUSSION AND CONCLUSIONS: Treatment with B. holophylla was associated with a marked hypoglycaemic effect through the stimulation of glycogenesis and inhibition of gluconeogenesis and intestinal glucose absorption, without increasing basal insulinaemia.

Optimized protocol for shotgun label-free proteomic analysis of pancreatic islets.

Pancreatic islets are crucial in diabetes research. Consequently, this protocol aims at optimizing both the protein-extraction process and the proteomic analysis via shotgun methods for pancreatic islets. Six protocols were tested, combining three types of chemical extraction with two mechanical extraction methods. Furthermore, two protocols incorporated a surfactant to enhance enzymatic cleavage. The steps involved extraction and concentration of protein, protein quantification, reduction, alkylation, digestion, purification and desalination, sample concentration to ∼1 µl, and proteomic analysis using the mass spectrometer. The most effective protocol involves either a milder chemical extraction paired with a more intensive mechanical process, or a more robust chemical extraction paired with a gentle mechanical process, tailored to the sample's characteristics. Additionally, it was observed that the use of a surfactant proved ineffective for these types of samples. Protocol 5 was recently used with success to examine metabolic changes in pancreatic islets of non-obese diabetic mice exposed to low doses of fluoride ions (F-) and the primary pathways altered by the treatment.

Maternal protein restriction combined with postnatal sugar consumption alters liver proteomic profile and metabolic pathways in adult male offspring rats.

This study investigated the impact of maternal protein restriction (MPR) and early postnatal sugar consumption (SUG) on the liver health of adult male descendant rats. Male offspring of mothers fed a normal protein diet (NPD) or a low protein diet (LPD) were divided into four groups: Control (CTR), Sugar Control (CTR + SUG), LPD during gestation and lactation (GLLP), and LPD with sugar (GLLP + SUG). Sugar consumption (10% glucose diluted in water) began after weaning on day 21 (PND 21), and at 90 days (PND 90), rats were sacrificed for analysis. Sugar intake reduced food intake and increased water consumption in CTR + SUG and GLLP + SUG compared to CTR and GLLP. GLLP and GLLP + SUG groups showed lower body weight and total and retroperitoneal fat compared to CTR and CTR + SUG. CTR + SUG and GLLP + SUG groups exhibited hepatocyte vacuolization associated with increased hepatic glycogen content compared to CTR and GLLP. Hepatic catalase activity increased in GLLP compared to CTR. Proteomic analysis identified 223 differentially expressed proteins (DEPs) among experimental groups. While in the GLLP group, the DEPs enriched molecular pathways related to cellular stress, glycogen metabolic pathways were enriched in the GLLP + SUG and CTR + SUG groups. The association of sugar consumption amplifies the effects of MPR, deregulating molecular mechanisms related to metabolism and the antioxidant system.

Diabetic older women without peripheral neuropathy amplify body sway but are capable of improving postural stability during a saccadic gaze task.

BACKGROUND: Diabetic older people tend to present deteriorated performance in balance and locomotion activities, even those without peripheral neuropathy. There is evidence that saccadic eye movements are used to reduce body sway in young and older healthy adults, but it has not been shown that diabetic older people preserve this visuomotor adaptation capacity. RESEARCH QUESTION: Are diabetic older women without peripheral neuropathy capable of improving postural stability during a saccadic gaze task? METHODS: Seventeen type 2 diabetic older women (68.2 ± 10.7 years old) and seventeen healthy women, age-matched controls (66.0 ± 8.4 years old) voluntarily participated in the study. All participants were instructed to stand upright, barefoot, as stable as possible, for 30 s. Participants maintained their feet parallel to each other, at standard and narrow bases of support, while either fixating on a stationary target (fixation condition) or performing horizontal saccadic eye movements to follow a target (eccentricity of 11° of visual angle), which continuously disappeared and reappeared immediately on the opposite side (saccade 0.5 Hz and saccade 1.1 Hz conditions). RESULTS: Results indicated that the diabetic group clearly had deteriorated postural control, as shown by increased values of mean sway amplitude and mean sway velocity. However, diabetic and control groups were similarly capable of using saccadic eye movements to improve their postural stability, reducing their sway velocity compared to a gaze fixation condition. SIGNIFICANCE: Diabetes per se (without peripheral neuropathy) amplifies postural sway of older women as compared to their healthy age-matched controls. However, diabetic older women without peripheral neuropathy are capable of improving postural stability during a saccadic gaze task.

Metabolic effect of low fluoride levels in the islets of NOD mice: integrative morphological, immunohistochemical, and proteomic analyses.

OBJECTIVES: Fluoride (F) has been widely used to control dental caries, and studies suggest beneficial effects against diabetes when a low dose of F is added to the drinking water (10 mgF/L). This study evaluated metabolic changes in pancreatic islets of NOD mice exposed to low doses of F and the main pathways altered by the treatment. METHODOLOGY: In total, 42 female NOD mice were randomly divided into two groups, considering the concentration of F administered in the drinking water for 14 weeks: 0 or 10 mgF/L. After the experimental period, the pancreas was collected for morphological and immunohistochemical analysis, and the islets for proteomic analysis. RESULTS: In the morphological and immunohistochemical analysis, no significant differences were found in the percentage of cells labelled for insulin, glucagon, and acetylated histone H3, although the treated group had higher percentages than the control group. Moreover, no significant differences were found for the mean percentages of pancreatic areas occupied by islets and for the pancreatic inflammatory infiltrate between the control and treated groups. Proteomic analysis showed large increases in histones H3 and, to a lesser extent, in histone acetyltransferases, concomitant with a decrease in enzymes involved in the formation of acetyl-CoA, besides many changes in proteins involved in several metabolic pathways, especially energy metabolism. The conjunction analysis of these data showed an attempt by the organism to maintain protein synthesis in the islets, even with the dramatic changes in energy metabolism. CONCLUSION: Our data suggests epigenetic alterations in the islets of NOD mice exposed to F levels comparable to those found in public supply water consumed by humans.

Vochysia tucanorum Mart. butanol fraction presents antitumoral activity in vivo and prevents the installation of cachexia in solid Ehrlich tumor model.

BACKGROUND: Cancer is a multifactorial disease caused by uncontrolled proliferation of cells. About 50-80% of cancer patients develop cachexia, a complex metabolic syndrome associated with an increase of mortality and morbidity. However, there are no effective therapies in medical clinic for cancer cachexia. Vochysia tucanorum Mart. is a common three of the Brazilian "Cerrado". The butanolic fraction of V. tucanorum (Fr-BuVt), very rich in triterpenes with various biological activities, might be interesting in being tested in cancer cachexia syndrome. Hence, the present study was undertaken to investigate the antitumoral activity of Fr-BuVt and its potential against cachexia development. METHODS: Ehrlich tumor was used as model of cancer cachexia. Ascitic Ehrlich tumor cells were collected, processed and inoculated subcutaneously in saline solution (1 × 107/100 µl; ≥95% viability) for the obtention of solid Ehrlich carcinoma. After inoculation, solid Ehrlich carcinoma-bearing mice were treated by 14 consecutive days by gavage with Fr-BuVt (200 mg/kg). Body weight and tumor volume were measure during the treatment period. Tumors were removed, weighed and properly processed to measure the content and phosphorylation levels of key-proteins involved to apoptotic and proliferation process by Western Blot. Muscles and adipose tissues were removed for weighed. Serum was collected to cytokines levels and energetic blood markers measurements. RESULTS: The treatment with the Fr-BuVt (200 mg/kg, 14 days) decreased the solid Ehrlich tumor volume and weight besides increased the expression of the pro-apoptotic proteins caspase-3 and BAX, but also decreased the expression of the proteins involved in proliferation NFκB, mTOR and ERK. In addition, our data shows that the administration of Fr-BuVt was able to prevent the installation of cancer cachexia in Ehrlich carcinoma-bearing mice, since prevented the loss of body weight, as well as the loss of muscle and adipose tissue. Moreover, an improvement in some blood parameters such as decrease in cytokines TNF-α and IL-6 levels is observed. CONCLUSIONS: The study revealed that Fr-BuVt has antitumoral activity and prevent installation of cancer cachexia in Ehrlich model. Therefore, Fr-BuVt may represent an alternative treatment for cancer cachexia.

Hypoglycemic active principles from the leaves of Bauhinia holophylla: Comprehensive phytochemical characterization and in vivo activity profile.

Bauhinia holophylla leaves, also known as "pata-de-vaca", are traditionally used in Brazil to treat diabetes. Although the hypoglycemic activity of this medicinal plant has already been described, the active compounds responsible for the hypoglycemic activity have not yet been identified. To rapidly obtain two fractions in large amounts compatible with further in vivo assay, the hydroalcoholic extract of B. holophylla leaves was fractionated by Vacuum Liquid Chromatography and then purified by medium pressure liquid chromatography combined with an in vivo Glucose Tolerance Test in diabetic mice. This approach resulted in the identification of eleven compounds (1-11), including an original non-cyanogenic cyanoglucoside derivative. The structures of the isolated compounds were elucidated by nuclear magnetic resonance and high-resolution mass spectrometry. One of the major compounds of the leaves, lithospermoside (3), exhibited strong hypoglycemic activity in diabetic mice at the doses of 10 and 20 mg/kg b.w. and prevents body weight loss. The proton nuclear magnetic resonance (1H NMR) quantification revealed that the hydroalcoholic leaves extract contained 1.7% of lithospermoside (3) and 3.1% of flavonoids. The NMR analysis also revealed the presence of a high amount of pinitol (4) (9.5%), a known compound possessing in vivo hypoglycemic activity. The hypoglycemic properties of the hydroalcoholic leaves extract and the traditional water infusion extracts of the leaves of B. holophylla seem thus to be the result of the activity of three unrelated classes of compounds. Such results support to some extent the traditional use of Bauhinia holophylla to treat diabetes.

Exercise training prevents hyperinsulinemia, muscular glycogen loss and muscle atrophy induced by dexamethasone treatment.

This study investigated whether exercise training could prevent the negative side effects of dexamethasone. Rats underwent a training period and were either submitted to a running protocol (60% physical capacity, 5 days/week for 8 weeks) or kept sedentary. After this training period, the animals underwent dexamethasone treatment (1 mg/kg per day, i.p., 10 days). Glycemia, insulinemia, muscular weight and muscular glycogen were measured from blood and skeletal muscle. Vascular endothelial growth factor (VEGF) protein was analyzed in skeletal muscles. Dexamethasone treatment evoked body weight loss (-24%), followed by muscular atrophy in the tibialis anterior (-25%) and the extensor digitorum longus (EDL, -15%). Dexamethasone also increased serum insulin levels by 5.7-fold and glucose levels by 2.5-fold compared to control. The exercise protocol prevented atrophy of the EDL and insulin resistance. Also, dexamethasone-treated rats showed decreased muscular glycogen (-41%), which was further attenuated by the exercise protocol. The VEGF protein expression decreased in the skeletal muscles of dexamethasone-treated rats and was unaltered by the exercise protocol. These data suggest that exercise attenuates hyperglycemia and may also prevent insulin resistance, muscular glycogen loss and muscular atrophy, thus suggesting that exercise may have some benefits during glucocorticoid treatment.

Effects of low-level fluoride exposure on glucose homeostasis in female NOD mice.

Water fluoridation is an important public health measure for the control of dental caries. Recent animal studies have shown that low doses of fluoride (F) in the drinking water, similar to those found in public water supplies, increase insulin sensitivity and reduce blood glucose. In the present study we evaluated the effects of low-level F exposure through the drinking water on glucose homeostasis in female NOD mice. Seventy-two 6-week mice were randomly divided into 2 groups according to the concentration of F in the drinking water (0-control, or 10 mg/L) they received for 14 weeks. After the experimental period the blood was collected for analyses of plasma F, glucose and insulin. Liver and gastrocnemius muscle were collected for proteomic analysis. Plasma F concentrations were significantly higher in the F-treated than in the control group. Despite treatment with fluoridated water reduced plasma levels glucose by 20% compared to control, no significant differences were found between the groups for plasma glucose and insulin. In the muscle, treatment with fluoridated water increased the expression of proteins related to muscle contraction, while in the liver, there was an increase in expression of antioxidant proteins and in proteins related to carboxylic acid metabolic process. Remarkably, phosphoenolpyruvate carboxykinase (PEPCK) was found exclusively in the liver of control mice. The reduction in PEPCK, a positive regulator of gluconeogenesis, thus increasing glucose uptake, might be a probable mechanism to explain the anti-diabetic effects of low doses of F, which should be evaluated in further studies.

Increased pancreatic islet mass is accompanied by activation of the insulin receptor substrate-2/serine-threonine kinase pathway and augmented cyclin D2 protein levels in insulin-resistant rats.

It is well known that glucocorticoids induce peripheral insulin resistance in rodents and humans. Here, we investigated the structural and ultrastructural modifications, as well as the proteins involved in beta-cell function and proliferation, in islets from insulin-resistant rats. Adult male Wistar rats were made insulin resistant by daily administration of dexamethasone (DEX; 1mg/kg, i.p.) for five consecutive days, whilst control (CTL) rats received saline alone. Structure analyses showed a marked hypertrophy of DEX islets with an increase of 1.7-fold in islet mass and of 1.6-fold in islet density compared with CTL islets (P < 0.05). Ultrastructural evaluation of islets revealed an increased amount of secreting organelles, such as endoplasmic reticulum and Golgi apparatus in DEX islets. Mitotic figures were observed in DEX islets at structural and ultrastructural levels. Beta-cell proliferation, evaluated at the immunohistochemical level using anti-PCNA (proliferating cell nuclear antigen), showed an increase in pancreatic beta-cell proliferation of 6.4-fold in DEX islets compared with CTL islets (P < 0.0001). Increases in insulin receptor substrate-2 (IRS-2), phosphorylated-serine-threonine kinase AKT (p-AKT), cyclin D(2) and a decrease in retinoblastoma protein (pRb) levels were observed in DEX islets compared with CTL islets (P < 0.05). Therefore, during the development of insulin resistance, the endocrine pancreas adapts itself increasing beta-cell mass and proliferation, resulting in an amelioration of the functions. The potential mechanisms that underlie these events involve the activation of the IRS-2/AKT pathway and activation of the cell cycle, mediated by cyclin D(2). These adaptations permit the maintenance of glycaemia at near-physiological ranges.

Prevention of Elevation in Plasma Triacylglycerol with High-Dose Bezafibrate Treatment Abolishes Insulin Resistance and Attenuates Glucose Intolerance Induced by Short-Term Treatment with Dexamethasone in Rats.

OBJECTIVE: Fibrates are used as lipid-lowering drugs and are well tolerated as cotreatments when glucose metabolism disturbances are also present. Synthetic glucocorticoids (GCs) are diabetogenic drugs that cause dyslipidemia, dysglycemia, glucose intolerance, and insulin resistance when in excess. Thus, we aimed to describe the potential of bezafibrate in preventing or attenuating the adverse effects of GCs on glucose and lipid homeostasis. METHODS: Male Wistar rats were treated with high-dose bezafibrate (300 mg/kg, body mass (b.m.)) daily for 28 consecutive days. In the last five days, the rats were also treated with dexamethasone (1 mg/kg, b.m.). RESULTS: Dexamethasone treatment reduced the body mass gain and food intake, and bezafibrate treatment exerted no impact on these parameters. GC treatment caused an augmentation in fasting and fed glycemia, plasma triacylglycerol and nonesterified fatty acids, and insulinemia, and bezafibrate treatment completely prevented the elevation in plasma triacylglycerol and attenuated all other parameters. Insulin resistance and glucose intolerance induced by GC treatment were abolished and attenuated, respectively, by bezafibrate treatment. CONCLUSION: High-dose bezafibrate treatment prevents the increase in plasma triacylglycerol and the development of insulin resistance and attenuates glucose intolerance in rats caused by GC treatment, indicating the involvement of dyslipidemia in the GC-induced insulin resistance.

Metabolic effect of low fluoride levels in the islets of NOD mice: integrative morphological, immunohistochemical, and proteomic analyses

Abstract Fluoride (F) has been widely used to control dental caries, and studies suggest beneficial effects against diabetes when a low dose of F is added to the drinking water (10 mgF/L). Objectives This study evaluated metabolic changes in pancreatic islets of NOD mice exposed to low doses of F and the main pathways altered by the treatment. Methodology In total, 42 female NOD mice were randomly divided into two groups, considering the concentration of F administered in the drinking water for 14 weeks: 0 or 10 mgF/L. After the experimental period, the pancreas was collected for morphological and immunohistochemical analysis, and the islets for proteomic analysis. Results In the morphological and immunohistochemical analysis, no significant differences were found in the percentage of cells labelled for insulin, glucagon, and acetylated histone H3, although the treated group had higher percentages than the control group. Moreover, no significant differences were found for the mean percentages of pancreatic areas occupied by islets and for the pancreatic inflammatory infiltrate between the control and treated groups. Proteomic analysis showed large increases in histones H3 and, to a lesser extent, in histone acetyltransferases, concomitant with a decrease in enzymes involved in the formation of acetyl-CoA, besides many changes in proteins involved in several metabolic pathways, especially energy metabolism. The conjunction analysis of these data showed an attempt by the organism to maintain protein synthesis in the islets, even with the dramatic changes in energy metabolism. Conclusion Our data suggests epigenetic alterations in the islets of NOD mice exposed to F levels comparable to those found in public supply water consumed by humans.

Myrcia bella Leaf Extract Presents Hypoglycemic Activity via PI3k/Akt Insulin Signaling Pathway.

Species of Myrcia are used by indigenous people and in traditional communities in Brazil for the treatment of Diabetes mellitus. We investigated the hypoglycemic effect of the extract of leaves of Myrcia bella in diabetic mice. The chemical fingerprinting of the 70% EtOH extract characterized as main constituents flavonoid aglycones, flavonoid-O-glycosides, and acylated flavonoid-O-glycosides derivatives of quercetin and myricetin. Mice were treated with saline or extract of M. bella (300 or 600 mg/Kg b.w.) for 14 days. Body weight and water and food intake were measured every day. Fasting blood glucose was measured weekly. At the end of the treatment, blood insulin, triglycerides, total cholesterol, and protein were measured. Glycogen content and expression of proteins of the insulin signaling pathway were measured in liver. The treatment with 600 mg/Kg reduced the fasting blood glucose in diabetic mice of the 7th day as water and food intake and increased hepatic glycogen. Total cholesterol and triglycerides were reduced in diabetic treated mice. The treatment increased the expression of IRS-1, PI3-K, and AKT in the livers of diabetic treated mice. The results indicate that the extract of the leaves of Myrcia bella has hypoglycemic properties and possibly acts to regulate glucose uptake by the liver.

High-fat diet obesity associated with insulin resistance increases cell proliferation, estrogen receptor, and PI3K proteins in rat ventral prostate.

In this study, we evaluated the effects of obesity and insulin resistance induced by a high-fat diet on prostate morphophysiology, focusing on cell proliferation, expression of androgen (AR) and estrogen receptors (ER) and proteins of the insulin signaling pathway. Adult male Wistar rats were fed a high-fat diet (20% fat) for 15 weeks, whereas control animals received a balanced diet (4% fat). Both groups were then divided and treated for 2 weeks with 1 mg/kg body weight/day of the aromatase inhibitor letrozole or vehicle only. The ventral prostate was analyzed with immunohistochemical, histopathological, stereological, and Western blotting methods. Obese rats showed insulin resistance, hyperinsulinemia, and reduced plasma testosterone levels. The incidence of prostatic intraepithelial neoplasia (PIN) was 2.7 times higher in obese rats and affected 0.4% of the gland compared with 0.1% PIN areas found in control rats. Obesity doubled cell proliferation in both prostate epithelium and stroma. AR content decreased in the prostate of obese rats and estrogen receptor beta (ERß) increased in this group. Protein levels of insulin receptor substrate 1 and protein kinase B diminished in the obese group, whereas phosphatidylinositol 3-kinase (PI3K) increased significantly. Most structural changes observed in the prostate of obese rats normalized after letrozole treatment, except for increased stromal cell proliferation and ERß expression, which might be associated with insulin resistance. This experimental model of obesity and insulin resistance induced by a high-fat diet increases cell proliferation in rat prostate. Such alterations are associated with decreased levels of AR and increased ERß and PI3K proteins. This change can facilitate the establishment of proliferative lesions in rat prostate.

Involvement of the cholinergic pathway in glucocorticoid-induced hyperinsulinemia in rats.

AIMS: We investigated the contribution of the cholinergic nervous system to dexamethasone-induced insulin resistance and hyperinsulinemia in rats. METHODS: Seventy-day-old Wistar male rats were distributed in groups: control (CTL), vagotomized (VAG), and sham operated (SHAM). On the 90th day of life, half of the rats were treated daily with 1mg/kg of dexamethasone for 5 days (CTL DEX, VAG DEX, and SHAM DEX). RESULTS: In the presence of 8.3mM glucose plus 100microM carbachol (Cch), isolated islets from CTL DEX secreted significantly more insulin than CTL. Cch-enhancement of secretion was further increased in islets from VAG CTL and VAG DEX than SHAM CTL and SHAM DEX, respectively. In CTL DEX islets, M3R and PLCbeta1 and phosphorylated PKCalpha, but not PKCalpha, protein content was significantly higher compared with each respective control. In islets from VAG DEX, the expression of M3R protein increased significantly compared to VAG CTL and SHAM DEX. Vagotomy per se did not affect insulin resistance, but attenuated fasted and fed insulinemia in VAG DEX, compared with SHAM DEX rats. CONCLUSION: These data indicate an important participation of the cholinergic nervous system through muscaric receptors in dexamethasone-induced hyperinsulinemia in rats.

Efeitos da administração de dexametasona in vivo sobreglicemia, insulinemia e substratos circulantes sãodependentes do tempo de tratamento / Effects of dexamethasone administration in vivo on glycaemia, insulinaemia and circulating substrates are dependents of timeof treatment

Terapias a base de glicocorticóides estão freqüentemente associadas a alteração da sensibilidade à insulina. No presente trabalho avaliamos alguns parâmetros metabólicos como glicose, insulina, proteínas e colesterolplasmáticos em ratos tratados com dexametasona (DEX) (1mg/kg, peso corpóreo, ip.) por diferentes períodos de tempo (24h, 72h e 120h). Os ratos tratados com dexametasona apresentaram resistência periférica à insulina após 24h de administração da droga como indicam os valores de insulina plasmática de jejum (1,3 vs. 6,8 ng/ml para ratos controle [CTL] e DEX, respectivamente) e do índice HOMA. Resistência periférica à insulina adicional ocorre até o final do tratamento nos ratos DEX. A glicemia permanece moderadamente elevada até o período de 72h. Entretanto, observa-se marcante hiperglicemia após 120h (79 vs. 160 mg/dl para ratos CTL e DEX, respectivamente). Aumento significativo dos níveis de proteínas totais e albuminas plasmáticas ocorre a partir de 72h de tratamento e de colesterol total a partir de 120h. Glicogênio e gordura hepáticos aumentam de maneira tempo-dependente nos ratos DEX. Correlação negativa foi observada entre os valores de insulinemia de jejum e peso nos grupos tratados com dexametasona (r > 0,95). Portanto, administração de dexametasona, 1mg/kg, induz resistência periférica à insulina de maneira tempo-dependente a partir de 24h e aumento dos níveis circulantes de glicose e proteínas plasmáticos após 72h de tratamento.

Glucocorticoid therapies are often associated with insulin sensitivity alteration. In the present study we evaluated some metabolical parameters such as plasma glucose, insulin, protein and cholesterol levels in ratstreated with dexamethasone (DEX) (1mg/kg, body weight, ip.) in different periods (24h, 72h and 120h). Dexamethasonetreated rats show peripherical resistance after 24h of drug administration as indicated by the fasting plasma insulin values (1.3 vs.6.8 ng/ml for controls [CTL] and DEX rats, respectively) and by HOMA index. Additional peripheral insulin resistance occurred until the end of treatment in DEX rats. The glycaemia remained slightly elevated until 72h period. However, marked hyperglycaemia was observed after 120h (79 vs.160 mg/dl for CTL and DEX rats, respectively). Significantly increase of plasma albumin and total proteins levels occurred from 72h of treatment and total cholesterol from 120h. Hepatic glycogen and hepatic fat increased in a time-dependent manner in DEX rats. Negative correlation was observed between fasting insulin and body weight values in dexamethasone-treated groups (r > 0.95). Therefore, dexamethasone administration, 1mg/kg, induces insulin peripheral resistance in a time-dependent manner from 24h and increase of circulating plasma glucose and proteins levels after 72h of treatment.