Our objective was to establish a diabetes mellitus type 2 (DM2) model in rats using a high-fat diet and streptozotocin (HF-STZ). Male Wistar rats (240-250g) were divided into a control group ...(commercial feed), and HF-STZ group, (66.5%-commercial feed, 13.5%-lard, and 20%-sugar). STZ (40mg/kg i.p.) or vehicle was administered on the 13th day. An oral glucose tolerance test (OGTT) was performed (2.5mg of glucose/kg v.o.) on both groups. After 39 days of treatment, blood and tissue samples were collected for analyses. The weight gain after STZ administration was lower in the HF-STZ group than in the control group with reductions in muscle mass and adipose tissue. The HF-STZ group showed hyperglycemia after STZ administration (glucose on day 39: HF-STZ: 499 ± 60; control: 134 ± 9mg/dL). Serum glucagon was 23% lower, and insulin levels were unaltered. The HOMA index was 4-times higher in the HF-STZ. The HF-STZ group showed increased post-prandial (330%) and fasting (125%) triglycerides, and while glycogen content in the liver and muscles decreased (70-80%). The area under the curve (OGTT) was 282% higher in the HF-STZ group. The combination of high-fat diet with STZ (i.p) generated rats with hyperglycemia associated with hypertriglyceridemia and introduced many other alterations present in human DM2.
The aim of this study was investigate the effects of a low-protein, high-carbohydrate (LPHC) diet introduced to rats soon after weaning. The animals were distributed in the following groups: LPHC45: ...fed an LPHC diet (6%-protein, 74%-carbohydrate) for 45 days; C45: fed a control (C) diet (17%-protein, 63%-carbohydrate) for 45 days; R (Reverse): fed with LPHC for 15 days followed by C diet for 30 days. The LPHC45 group showed alterations in the energetic balance with an increase in brown adipose tissue, and in glucose tolerance, and lower final body weight, muscle mass and total protein in blood when compared with C45 group. The HOMA-IR index was similar between LPHC45 and C45 groups, but this parameter was lower in LPHC45 compared with R groups. Serum adiponectin was higher in LPHC45 group than C45 and R groups. The R group presented higher fed insulin than C45 and LPHC45 and higher T4 compared with C45 group. Total cholesterol in R group was higher when compared with LPHC45 group. Thus, the data show that the change of the diet LPHC for a balanced diet led to different metabolic evolution and suggest that the different response can be due to different levels of adiponectin.
A low-protein, high-carbohydrate (LPHC) diet for 15 days increased the lipid content in the carcass and adipose tissues of rats. The aim of this work was to investigate the mechanisms of this lipid ...increase in the retroperitoneal white adipose tissue (RWAT) of these animals. The LPHC diet induced an approximately two- and tenfold increase in serum corticosterone and TNF-α, respectively. The rate of de novo fatty acid (FA) synthesis in vivo was reduced (50%) in LPHC rats, and the lipoprotein lipase activity increased (100%). In addition, glycerokinase activity increased (60%), and the phosphoenolpyruvate carboxykinase content decreased (27%). Basal U-
14
C-glucose incorporation into glycerol-triacylglycerol did not differ between the groups; however, in the presence of insulin, U-
14
C-glucose incorporation increased by 124% in adipocytes from only control rats. The reductions in IRS1 and AKT content as well as AKT phosphorylation in the RWAT from LPHC rats and the absence of an insulin response suggest that these adipocytes have reduced insulin sensitivity. The increase in NE turnover by 45% and the lack of a lipolytic response to NE in adipocytes from LPHC rats imply catecholamine resistance. The data reveal that the increase in fat storage in the RWAT of LPHC rats results from an increase in FA uptake from circulating lipoproteins and glycerol phosphorylation, which is accompanied by an impaired lipolysis that is activated by NE.
Tapioca starch (TS) is produced from Cassaca roots and it is differentiated from other starches because it contains about 17-20% amylase and low amount of residual substances. Propranolol (POP) is a ...non-selective beta-adrenergic blocking agent and it is in the World Health Organization's List of Essential Medicines. The aim of this work was to investigate the potential of TS in the development of POP tablets by means of direct compression. Its evaluation was performed by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR) relaxometry, scanning electron microscopy (SEM), uniformity of weight, drug content, disintegration, friability, hardness, dissolution test and drug release kinetics. The TS granules were spherical with mean diameter of 10.09 ± 1.85 µm. The XRD, FTIR and NMR suggested physical interaction between TS and POP. The tablets presented average diameter of 1.1 ± 0.0 cm, 0.24 ± 0.02 cm thickness and average weight of 0.544 ± 0.003 g. The hardness of tablets was 10.98 ± 0.31 N and the percentage of friability was 25.74 ± 0.08%. POP was released after 45 min and the release kinetics properly fitted the Hixson-Crowell equation.
In the present paper the anti-diabetic effects of stem-bark extract (ethanol 70%) of
Vatairea macrocarpa, a traditional diabetes mellitus treatment widely used in Brazil, are reported. The extract ...was administered orally at a dose of 250 or 500
mg/kg, for 22 days, to normal and streptozotocin-diabetic rats. In extract treated (500
mg/kg) diabetic rats serum and urinary glucose, urinary urea, food and fluid intake were decreased, while body weight gain was increased, all of which indicate an improvement in diabetic state (
p
<
0.05). No effects of the extract were observed in non-diabetic rats. In extract treated (500
mg/kg) diabetic group HOMA-R (homeostasis model for assessment of insulin resistance) was lower at the end of 22 days, as compared to diabetic non treated control group. Insulin was the reference substance used in the experiments. In an oral glucose tolerance test, the time to reach maximal glycemia was greater in diabetic 500
mg/kg treated group than in control group. These anti-diabetic effects could be related to an improved insulin resistance, although a possible effect on pancreatic B-cell function cannot be excluded. Thus, our data of sub-chronic experiments suggest that long-term use of
V. macrocarpa stem-bark extract may be helpful in treating diabetic conditions.
The aim of this study was to evaluate thermogenesis in the interscapular brown adipose tissue (IBAT) of rats submitted to low-protein, high-carbohydrate (LPHC) diet and the involvement of adrenergic ...stimulation in this process. Male rats (~100 g) were submitted to LPHC (6 %-protein; 74 %-carbohydrate) or control (C; 17 %-protein; 63 %-carbohydrate) isocaloric diets for 15 days. The IBAT temperature was evaluated in the rats before and after the administration of noradrenaline (NA) (20 µg 100 g b w⁻¹ min⁻¹). The expression levels of uncoupling protein 1 (UCP1) and other proteins involved in the regulation of UCP1 expression were determined by Western blot (Student’s t test, P ≤ 0.05). The LPHC diet promoted a 1.1 °C increase in the basal temperature of IBAT when compared with the basal temperature in the IBAT of the C group. NA administration promoted a 0.3 °C increase in basal temperature in the IBAT of the C rats and a 0.5 °C increase in the IBAT of the LPHC group. The level of UCP1 increased 60 % in the IBAT of LPHC-fed rats, and among the proteins involved in its expression, such as β3-AR and α1-AR, there was a 40 % increase in the levels of p38-MAPK and a 30 % decrease in CREB when compared to the C rats. The higher sympathetic flux to IBAT, which is a consequence of the administration of the LPHC diet to rats, activates thermogenesis and increases the expression of UCP1 in the tissue. Our results suggest that the increase in UCP1 content may occur via p38 MAPK and ATF2.
The our objective was to investigate the adaptations induced by a low-protein, high-carbohydrate (LPHC) diet in growing rats, which by comparison with the rats fed a control (C) diet at displayed ...lower fasting glycemia and similar fasting insulinemia, despite impairment in insulin signaling in adipose tissues. In the insulin tolerance test the LPHC rats showed higher rates of glucose disappearance (30%) and higher tolerance to overload of glucose than C rats. The glucose uptake by the soleus muscle, evaluated in vivo by administration of 2-deoxy-
14
Cglucose, increased by 81%. The phosphoenolpyruvate carboxykinase content and the incorporation of 1-
14
Cpyruvate into glucose was also higher in the slices of liver from the LPHC rats than in those from C rats. The LPHC rats showed increases in
l
-lactate as well as in other gluconeogenic precursors in the blood. These rats also had a higher hepatic production of glucose, evaluated by in situ perfusion. The data obtained indicate that the main substrates for gluconeogenesis in the LPHC rats are
l
-lactate and glycerol. Thus, we concluded that the fasting glycemia in the LPHC animals was maintained mainly by increases in the hepatic gluconeogenesis from glycerol and
l
-lactate, compensating, at least in part, for the higher glucose uptake by the tissues.
The aim of this study was to investigate tumor necrosis factor alpha (TNF-α)- and noradrenaline (NE)-stimulated lipolysis in retroperitoneal (RWAT) and epididymal (EAT) white adipose tissue as a ...means of understanding how low-protein, high-carbohydrate (LPHC) diet-fed rats maintain their lipid storage in a catabolic environment (marked by increases in serum TNF-α and corticosterone and sympathetic flux to RWAT and EAT), as previously observed. Adipocytes or tissues from the RWAT and EAT of rats fed an LPHC diet and rats fed a control (C) diet for 15 days were used in the experiments. The adipocytes from both tissues of the LPHC rats exhibited lower TNF-α- stimulated lipolysis compared to adipocytes from the C rats. The intracellular lipolytic agents IBMX, DBcAMPc and FSK increased lipolysis in both tissues from rats fed the C and LPHC diets compared to basal lipolysis; however, the effect was approximately 2.5-fold lower in adipocytes from LPHC rats. The LPHC diet induced a marked reduction in the β
3
and α
2
-AR, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) content in RWAT and EAT. The LPHC diet did not affect TNF-α receptor 1 content but did induce a reduction in ERK p44/42 in both tissues. The present work indicates that RWAT and EAT from LPHC rats have an impairment in the lipolysis signaling pathway activated by NE and TNF-α, and this impairment explains the reduced response to these lipolytic stimuli, which may be fundamental to the maintenance of lipid storage in LPHC rats.
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•Lecitase properties were modulated via immobilization.•Immobead-350 was activated with epoxy, divinylsulfone or glutaraldehyde groups.•All biocatalysts kept about 80% of their ...activity after 30 days of storage at 4 °C.•Enantio-specify versus R/S-methyl mandelate depended on the Leci biocatalysts.
Lecitase Ultra (Leci) was immobilized on Immobead-350 (IB-350) activated with epoxy (EPO), amino-divinylsulfone (DVS) or amino-glutaraldehyde (GLU) groups. Leci-GLU had 27% more activity versus p-nitro-phenyl butyrate (p-NPB) than Leci-EPO, after 3 h of immobilization using 100 mg of enzyme/g of support (immobilization yield was 84.1%, expressed activity versus p-NPB was around 10%), the covalent immobilization was show for Leci-GLU and Leci-DVS. After 10 consecutive cycles of p-NPB hydrolysis, its activity remained unaltered. Leci-GLU was the most stable preparation at 65 °C and pH 7 (29 folds more stable than the free enzyme) and in the presence of 30% acetonitrile at 30 °C and pH 7 (almost 2 folds more stable than the free enzyme). Very interestingly, the activity versus methyl mandelate and synthesis of benzyl acetate was quite high. Although the other biocatalysts had preference for the S-methyl mandelate, Leci-GLU preferred the R-isomer at pHs 5 (VR/VS = 6.6) and 7 (VR/VS = 3.5). In the enzymatic synthesis of benzyl acetate, the most active biocatalyst was also Leci-GLU (2.1 U/mg), being almost 2 folds more active than Leci-DVS. According to the results, it was concluded that the Lecitase immobilization on IB-350 using different chemistries greatly influenced its catalytic properties.
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