MK-626, a dipeptidyl peptidase-4 inhibitor, does not improve the hyperglycemia or hyperinsulinemia of nonobese diabetic MKR mice.

Dipeptidyl peptidase-4 (DPP-4) inhibitors increase circulating levels of incretin hormones, which can enhance insulin secretion and ß cell function. The aim of this study was to evaluate the effectiveness of MK-626 (a novel DPP-4 inhibitor) to reduce the hyperglycemia and hyperinsulinemia of nonobese type 2 diabetic MKR mice. Twelve to 14-week-old hyperglycemic MKR mice were gavaged daily with MK-626 (3 mg/kg body weight) or vehicle (0.5% methyl cellulose (MC)) for 2 weeks. MK-626-treated mice displayed no change in body weight or adverse reactions, suggesting good tolerance of the drug. Fed blood glucose was significantly reduced over the 2-week experiment; however, it was also reduced in the MC group, suggesting an effect of gavage alone. Fed plasma insulin and glucagon levels and glucose tolerance of MK-626-treated mice were similar to those of MC mice. Therefore, treatment with MK-626 did not correct the prolonged hyperglycemia and impaired glucose tolerance of MKR mice.

Lipocalin-2 counteracts metabolic dysregulation in obesity and diabetes.

Regulation of food intake is a recently identified endocrine function of bone that is mediated by Lipocalin-2 (LCN2). Osteoblast-secreted LCN2 suppresses appetite and decreases fat mass while improving glucose metabolism. We now show that serum LCN2 levels correlate with insulin levels and ß-cell function, indices of healthy glucose metabolism, in obese mice and obese, prediabetic women. However, LCN2 serum levels also correlate with body mass index and insulin resistance in the same individuals and are increased in obese mice. To dissect this apparent discrepancy, we modulated LCN2 levels in mice. Silencing Lcn2 expression worsens metabolic dysfunction in genetic and diet-induced obese mice. Conversely, increasing circulating LCN2 levels improves metabolic parameters and promotes ß-cell function in mouse models of ß-cell failure acting as a growth factor necessary for ß-cell adaptation to higher metabolic load. These results indicate that LCN2 up-regulation is a protective mechanism to counteract obesity-induced glucose intolerance by decreasing food intake and promoting adaptive ß-cell proliferation.

Whole blood aggregation and coagulation in db/db and ob/ob mouse models of type 2 diabetes.

Type 2 diabetes in humans is associated with a significant hypercoagulable state; however, the effects of this on stroke and cardiovascular disease are not completely understood. The genetic mutations in db/db and ob/ob mice produce metabolic abnormalities similar to type 2 diabetes, but little is known about their platelet or coagulation properties. The objective of this study was therefore to examine platelet function and coagulation in db/db and ob/ob mice to determine the degree of alteration induced by type 2 diabetes. Male db/db and ob/ob mice, 8-16 weeks old, and their respective genetic control mice were used for all experiments. To examine platelet function and coagulation, we measured ADP-induced whole blood aggregation at baseline and after inhibition with aspirin and fucoidan, whole blood coagulation by thromboelastography, and platelet CD61 expression by flow cytometry. Both db/db and ob/ob mice demonstrated significantly less ADP-induced whole blood aggregation compared with control mice (db/db mice, P < 0.001; ob/ob mice, P < 0.01). Aggregation was significantly inhibited with aspirin in all groups; however, fucoidan inhibited aggregation only in control mice. The db/db and ob/ob mice demonstrated significantly less maximal clot strength compared with control mice (P < 0.01), and ob/ob mice demonstrated premature clot fibrinolysis measured by thromboelastography. In conclusion, the db/db and ob/ob type 2 diabetes mouse models do not demonstrate a hypercoagulable state similar to humans with this disease. We caution their use for studying cardiovascular and cerebrovascular disease in the setting of type 2 diabetes.

Royal jelly improves hyperglycemia in obese/diabetic KK-Ay mice.

The study examined whether royal jelly (RJ) can prevent obesity and ameliorate hyperglycemia in type 2 diabetes. This study utilized obese/diabetic KK-Ay mice. RJ (10 mg/kg) was administered by oral gavage. Body weight, plasma glucose and insulin levels were measured. mRNA and protein levels were determined using quantitative reverse transcription polymerase chain reaction and western blotting, respectively. Four weeks of RJ administration improved hyperglycemia and partially suppressed body weight gain, although the latter effect did not reach statistical significance. In addition, RJ administration did not improve insulin resistance. RJ administration suppressed the mRNA expression of glucose-6-phosphatase (G6Pase), a key enzyme of gluconeogenesis, in the liver. Simultaneously, RJ administration induced adiponectin (AdipoQ) expression in abdominal fat, adiponectin receptor-1 (AdipoR1) expression in the liver and phosphorylated AMP-activated protein kinase (pAMPK) expression, which suppressed G6Pase levels in the livers of KK-Ay mice. pAMPK levels were also increased in skeletal muscle, but glucose transporter-4 (Glut4) translocation was not increased in the RJ supplementation group. The improvement in hyperglycemia due to long-term RJ administration may be because of the suppression of G6Pase expression through the upregulation of AdipoQ and AdipoR1 mRNA and pAMPK protein expressions.

Liver alpha-amylase gene expression as an early obesity biomarker.

BACKGROUND: Obesity is a major health problem worldwide, for which preventive and therapeutic means are still needed. Alpha-amylase is a digestive enzyme whose inhibition has been targeted as a potential anti-obesity strategy. However, alpha-amylase gene expression has not been particularly attended to, and in contrast with pancreatic and salivary amylases, fewer studies have focused on liver alpha-amylase. The present study aimed at investigating the expression of alpha-amylase gene in obese and normal mice at RNA and protein level as well as acarbose effect on this gene expression in hepatocyte cell culture. METHODS: Control and case groups were fed by normal mouse pellet and high-fat diet respectively, during 8 weeks. After this period, serum biochemical parameters including glucose, cholesterol, triglycerides, AST, ALT and alpha-amylase were assayed. Liver alpha-amylase gene was analyzed by real time PCR, and liver enzyme was assayed with Bernfeld and ELISA methods Hepatocyte cell culture derived from both group were also treated by acarbose and alpha-amylase activity and gene expression was analyzed by above mentioned methods. RESULTS: All biochemical factors showed an increase in obese mice, but the increase in ALT and AST were not statistically significant. Alpha-amylase levels were also increased in obese mice, both at RNA and protein level, while a decrease was seen in obese mice derived hepatocytes after acarbose treatment. CONCLUSIONS: Elevated liver alpha-amylase levels may be indicative of initial stages of obesity and the use of acarbose could be considered as a treatment of obesity which could be potentially effective at multiple levels.

Serum lipoprotein and apolipoprotein profiles of the genetically obese ob/ob mouse.

The lipid transport system of 3-month-old male C57BL/6J obese (ob/ob) mice was investigated. Serum lipoproteins were separated by density gradient ultracentrifugation and characterized by their chemical and electrophoretic properties as well as their relative apolipoprotein contents, defined according to molecular weight and charge. Obese, ob/ob mice exhibited a marked hyperlipoproteinemia resulting from large increases in low-density lipoproteins (LDL, d 1.021-1.058 g/ml) and high-density lipoproteins (HDL, d 1.058-1.137 g/ml), particularly, the HDL2 subclass (d 1.058-1.109 g/ml). This increase in lipoproteins was entirely responsible for their hypercholesterolemia and hyperphospholipidemia. By contrast, these obese mice had a net decrease in very-low-density lipoproteins (VLDL, d less than 1.016 g/ml) and intermediate-density lipoproteins (IDL, d 1.016-1.021 g/ml), which accounted for their moderate hypotriglyceridemia. The chemical composition of heterogeneous light LDL (d 1.021-1.040 g/ml and dense LDL (d 1.040-1.058 g/ml) overlapped by HDL-like particles was highly modified. These modifications consisted of increases in the percentages of cholesteryl ester and phospholipid and decreases in that of triacylglycerol. There were also marked changes in the relative values of the apolipoproteins of VLDL, but principally, IDL and LDL. IDL and light LDL were poorer in apolipoproteins BH (Mr 340,000-320,000) and eventually in apolipoprotein BL (Mr 220,000-200,000) and enriched in apolipoproteins E (Mr 37,000-35,000) and C-A-II (Mr approximately equal to 12,000). A similar and very significant change occurred in VLDL for both the apolipoproteins BL and C-A-II. Dense LDL, mainly poorer in apolipoprotein BH and enriched in apolipoprotein A-I (Mr 28,000-27,000), closely resembled HDL2 in all the groups, and were enriched in apolipoproteins C-A-II in only the obese mice. We suggest that ob/ob mice are probably protected against atheromata because of the low VLDL and IDL levels, and the increase in HDL2.

Platelet aggregation in the cerebral and mesenteric microcirculation of mice with genetically determined diabetes.

Platelet aggregates were induced in pial arterioles of the following strains of mice with a genetic predisposition for diabetes: ob/ob and db+/db+. Aggregation was compared with that in 6J+/+ mice, the nondiabetic controls for ob/ob animals, and in +m/+m as well as db+/+m, the nondiabetic controls for db+/db+ mice. Aggregation was also induced within mesenteric arterioles of db+/db+ animals and compared with that in db+/+m mice. Aggregation was monitored microscopically, by measuring the time required for a noxious stimulus to initiate aggregation in an injured arteriole. Platelet aggregation was initiated with equal ease in the pial arterioles of ob/ob mice and their 6J+/+ controls. However, the onset of aggregation in the pial arterioles of the db+/db+ group was significantly delayed when compared with the onset in either of the nondiabetic control groups, +m/+m or db+/+m. A similar prolongation in the time required to produce aggregation was also observed in the mesenteric arterioles of the db+/db+ mice when compared with db+/+m controls. The basis for reduced platelet aggregation in the microcirculation of db+/db+ mice is not explained. The results differ from those showing enhanced aggregation in many in vitro studies of platelets from human diabetics and from those of in vivo studies of two other animal models described in the literature. However, not all published studies have reported enhanced aggregation. The delayed aggregation in the present study may provide a basis for analysis of factors that regulate platelet aggregation in diabetes.

Abnormalities of GIP in spontaneous syndromes of obesity and diabetes in mice.

The role of GIP in the pathogenesis of spontaneous syndromes of obesity-diabetes was examined in ob/ob mice of the Aston stock and db/db mice of the C57BL/KsJ background. Compared with lean controls, fed adult ob/ob and db/db mice, respectively, exhibited 1.8-fold and 2.1-fold increases in body weight, 1.8-fold and 2.8-fold elevations of plasma glucose, and 15.4-fold and 5.6-fold elevations of plasma insulin. As indicated by the relative magnitude of the hyperglycemia and hyperinsulinemia, db/db mice displayed a particularly severe form of diabetes. Plasma GIP concentrations of ob/ob and db/db mice were elevated 15.1-fold and 6.2-fold, respectively; the increments closely corresponded with the degrees of hyperinsulinemia. Small intestinal weight was increased 1.4-fold and 1.8-fold in ob/ob and db/db mice, respectively, but the intestinal GIP content expressed as microgram/g intestine or microgram/intestine was raised only in ob/ob mice (1.9-fold and 2.8-fold, respectively). Since glucose stimulation of insulin release is defective in both mutant strains, the results strongly implicate pathologically raised GIP concentrations in the hyperinsulinemia and related metabolic abnormalities of the obesity-diabetes syndromes. It is suggested that hypersecretion of GIP results in part from loss of normal feedback inhibition by endogenous insulin.

Behavioral manipulation of the diabetic phenotype in ob/ob mice.

The genetically obese mouse (C57BL/6J ob/ob) is a commonly used model of non-insulin-dependent diabetes mellitus. However, our studies demonstrate that, while the animal is significantly hyperinsulinemic, it in fact does not show consistent hyperglycemia in the resting state. During stress, both obese animals and their lean littermates become hyperglycemic, but the magnitude of the hyperglycemia is exaggerated in the obese mice. Obese animals also show an exaggerated plasma glucose increase in response to epinephrine injection. This increase in plasma glucose is accompanied by a decrease in plasma insulin in response to both stress and epinephrine. Our findings suggest that environmental stimuli influence the expression of diabetes in the C57BL/6J obese mouse and therefore must be considered in studies of this animal model of diabetes.

Abnormal thyroid hormone binding to serum proteins in ob/ob and db/db genetically obese mice.

Sera from ob/ob and db/db genetically obese mice exhibited abnormal nonspecific (no antibody present) binding measurements in T4 and T3 RIAs employing dextran-charcoal separations. They also showed decreased charcoal uptake compared to sera of lean controls in a conventional charcoal T4 uptake binding test. After correction for the abnormal nonspecific binding and after extraction of serum, mean serum T4 concentrations were similar in control and ob/ob mice. Mean serum T3 concentrations differed significantly (85 ng/dl in controls and 178 ng/dl in ob/ob) when a correction for altered binding in the T3 assay was made, but not when extracted serum was assayed (109 ng/dl in lean and 124 ng/dl in ob/ob). Dialyzable fractions of T4 and T3 were significantly reduced in both ob/ob and db/db mice. Free T4 concentrations were 0.82 +/- 0.05 (+/- SE) ng/dl in control and 0.61 +/- 0.05 ng/dl in ob/ob sera (P less than 0.01). Polyacrylamide gel electrophoresis showed increased binding of tracer T4 and T3 in ob/ob and db/db sera to a postalbumin with mobility similar to that of human T4-binding globulin. In ob/ob sera, this appeared to result from an increased binding capacity of the postalbumin. After in vivo iv injection of tracer T4 and T3 to ob/ob and lean control mice, analysis of tissue and plasma radioactivity showed that, except for T4 in cerebral cortex, tissue to plasma T4 and T3 ratios were lower in cerebral cortex, cerebellum, and liver of ob/ob mice. In summary, these data show increased binding of T4 and T3 to a postalbumin in two strains of genetically obese mice and, in the ob/ob strain, complex relationships between tissue and serum concentrations of thyroid hormones.

Plasma immunoreactive gastric inhibitory polypeptide in obese hyperglycaemic (ob/ob) mice.

Gastric inhibitory polypeptide (GIP), a recognized component of the enteroinsular axis, is raised in the plasma and intestine of obese hyperglycaemic (ob/ob) mice. To evaluate the control of plasma GIP and its role in the hyperinsulinaemia of the ob/ob syndrome, GIP and insulin were determined at different ages in fed mice, and at 10-12 weeks of age after fasting/refeeding and administration of GIP, different nutrients and insulin to mice fasted for 18 h. Plasma GIP and insulin were raised in adult (10- and 20-week-old) compared with younger (3- and 5-week-old) mice, although GIP was not increased in the presence of hyperinsulinaemia at 3 weeks of age. Fasting suppressed and refeeding promptly restored plasma GIP and insulin concentrations. Administration of GIP to mimic postprandial concentrations evoked a marked but transient insulin response which was protracted in the presence of rising hyperglycaemia. Orally administered fat, glucose and amino acids raised GIP concentrations with fat having a particularly strong effect. Glucose and amino acids also evoked prominent increases of insulin, but fat produced only a small rise in insulin in the absence of increasing glucose concentrations. Consistent with glucose-potentiation, a mixture of all three nutrients greatly augmented the insulin response without further increase of plasma GIP. Glucose-induced increase in endogenous insulin and doses of exogenous insulin up to 100 units/kg did not suppress basal, fat-stimulated or glucose-stimulated GIP release. The results indicate that raised GIP concentrations make an important contribution to the hyperinsulinaemia and related metabolic abnormalities of the ob/ob syndrome.

Regulation of plasma immunoreactive glucagon in obese hyperglycaemic (ob/ob) mice.

This study examines the role of glucagon in the pathogenesis of the obese hyperglycaemic (ob/ob) syndrome in mice. Plasma C-terminal immunoreactive glucagon concentrations were measured in fed and fasted ob/ob mice at different ages between 5-40 weeks, and in 20-week-old mice after the administration of established stimulators and inhibitors of glucagon secretion. Plasma glucagon concentrations were inappropriately raised irrespective of age, nutritional status and the accompanying prominent changes in plasma glucose and insulin concentrations. Glucose suppressed plasma glucagon in the fed but not the fasted state, suggesting a dependence on the marked hyperinsulinaemia associated with feeding. Administration of 0.25 units insulin/kg to fasted mice failed to affect plasma glucagon and glucose concentrations. Increasing the dose to 100 units/kg restored the normal suppressive actions of insulin. Fasted mice showed an exaggerated glucagon response to arginine but not to the parasympathomimetic agent pilocarpine. Fed mice displayed normal plasma glucagon responses to the sympathomimetic agents noradrenaline and adrenaline. Administration of insulin antiserum or 2-deoxy-D-glucose raised plasma glucagon concentrations of fed mice. Contrary to the lack of suppression by glucose in the fasted state, heparin-induced increase in free fatty acids reduced plasma glucagon concentrations. This study demonstrates inappropriate hyperglucagonaemia and defective A-cell function in ob/ob mice. The extent of the abnormality is exacerbated by fasting and appears to result from insensitivity of the A-cell to the normal suppressive action of insulin.

Anti-hyperglycaemic action of BRL 26830, a novel beta-adrenoceptor agonist, in mice and rats.

BRL 26830, (R*,R*)-(+/-)-methyl 4-[2-[(2-hydroxy-2-phenylethyl)amino] propyl] benzoate, is a new orally active anti-hyperglycaemic agent. In 24 hr-fasted rats and mice, BRL 26830 decreased the blood glucose concentration following the administration of a subcutaneous glucose load. It also improved oral and intravenous glucose tolerance in 24 hr-fasted rats and decreased the post-prandial blood glucose concentration following the consumption of the complete, milk-based, meal "Nutrament". BRL 26830 produced a dose-related increase in the plasma insulin concentration and since it was inactive in lowering blood glucose in streptozotocin-diabetic rats, it is likely that its acute action on glucose tolerance was through the stimulation of insulin secretion. In contrast to the sulphonylurea, glibenclamide, BRL 26830 had no effect on the blood glucose concentration in 5 hr-fasted rats and only produced a transient reduction in 24 hr-fasted rats. BRL 26830 did not improve glucose tolerance when given acutely to hyperinsulinaemic C57BL/6 ob/ob mice. However, chronic treatment of these mice with BRL 26830 for 14-43 days resulted in a significant improvement in glucose tolerance.

Glucose and insulin response to conditioned feeding in lean and genetically obese hyperglycemic (ob/ob) mice.

The study reported here investigated the role of neuroendocrine reflexes in the stimulation of insulin secretion associated with feeding in lean and genetically obese hyperglycemic (ob/ob) mice. Twenty-week-old mice were conditioned over four weeks to restricted feeding periods of consecutively seven, four and two hours a day. Basal plasma glucose concentrations before feeding were raised in conditioned lean mice but lowered in conditioned ob/ob mice, with normalization of glycemia in ob/ob mice by four weeks. Conditioned mice consumed more food during the feeding period than control mice prefasted for the same time. Although the quantity of food consumed was less than the normal 24-hour intake of age-matched mice fed ad libitum, body weights were well maintained, indicating adaptations of metabolic efficiency or energy expenditure or both. During the feeding period, conditioned mice displayed a markedly enhanced plasma insulin response accompanied by a smaller increase in plasma glucose despite the consumption of more food. An anticipatory rise in plasma insulin was not evident when food was withheld during the prescribed two-hour feeding period after four weeks of conditioning. The results demonstrate that basal glucose concentrations were normalized in ob/ob mice but raised in lean mice by the restricted conditioned feeding procedure. Basal insulin concentrations and body weights were not significantly altered, but conditioning to expect food augmented the insulin response initiated by feeding in both lean and ob/ob mice.

The influence of plasma insulin concentrations on tissue insulin levels in rodents: a study of the diabetic Chinese hamster and the ob/ob mouse.

Immunoreactive insulin was measured in acid-ethanol extracts of kidney, brain, liver, and heart from genetically diabetic Chinese hamsters and their nondiabetic controls and from obese (ob/ob) mice and their thin littermates. Selected samples were filtered on Sephadex G-50 columns and the insulin concentration determined. There was a good correlation between the insulin level measured in the acid-ethanol extracts of tissues and the insulin level after gel filtration, suggesting that the concentration measured in the whole extract is representative of the true insulin content. The present data demonstrate that different extrapancreatic organs contain characteristic amounts of insulin that are often (sometimes several-fold) higher than the insulin level of plasma. The tissue insulin concentrations also exhibit a wide range of values, with occasional high values. The data also show a direct correlation between plasma and kidney insulins but no relationship between plasma and brain insulins and a mixed correlation among plasma and liver and heart insulins.

Repeated electroconvulsive shock normalizes blood glucose levels in genetically obese mice (C57BL/6J ob/ob) but not in genetically diabetic mice (C57BL/KsJ db/db).

There are several conflicting reports on the effect of electroconvulsive shock (ECS) on diabetes in humans. The present study investigated the effect of repeated ECS on blood glucose levels in genetically obese mice, which are considered an animal model for non-insulin dependent (maturity onset) diabetes. These mice were compared with genetically diabetic mice which are thought to be an animal model for insulin-dependent (juvenile-type) diabetes. A marked decrease in blood glucose concentrations was observed in obese mice after the first ECS which lasted for 14 days after the last ECS. No effect was seen in genetically diabetic mice. The neural mechanisms by which ECS normalizes blood glucose in genetically obese mice are discussed.

Some physiological characteristics of (SLN X C3H/He)F1 obese mice.

(SLN x C3H/He)F1 mice of both sexes showed significantly heavier body weights than the parental strains associated with the higher food intake and an accumulation of adipose tissue in the subcutaneous and the abdominal regions. Furthermore, serum levels of free fatty acid and growth hormone of F1 mice were higher and lower, respectively, than those of the parental strains. The results indicate that the obesity of these F1 mice is ascribed to excess food intake and metabolic disorders and they are promising as an animal model for the study of several diseases related to obesity.

Aislamiento de componentes y efecto hipoglicemiante del extracto metanólico de albahaca (Ocium basilicum), en ratas C57bl/6 con hiperglicemia experimental / Isolation of components and hypoglycemic effect of methanolic basil extract (ocium basilicum) in C57bl/6 rats with experimental hyperglycemia

ResumenAntecedentes:la albahaca (Ocium basilicum) es una hierba perteneciente a la familia laminaceae, caracterizada por sus bondades medicinales. Se ha referido su uso en la terapéutica del cáncer, vitíiigo, hipercolesterolemia y la diabetes mellitus.Objetivo:evaluar el efecto hipoglicemiante del extracto metanólico de la albahaca, su aislamiento y purificación de sus principales compuestos.Métodos:las hojas y tallos fueron colectadas en el sector la Hechicera, estado Mérida, Venezuela.Las muestras se maceraron en 20L de metanol al 70% v/v, dosificándose a dosis crecientes entre 1,0 y 2,0 g/kg, usando como modelo experimental, ratas macho de la cepa C57BL/6, con hiperglicemia inducida con aloxano monohidratado. Se incluyó un control positivo usando como agente hipoglucemiante la sitagliptina (400μg/kg). El extracto se sometió a fraccionamiento mediante cromatografía de columna abierta, cuyas fracciones (175 ml cada una) se asociaron por similitud estructural y fueron dosificadas a la población en estudio. Se obtuvieron muestras sanguíneas seriadas de la vena de la base de la cola y se procesaron siguiendo el método de la glucosa oxidasa-peroxidasa.Resultados:se demostró una disminución de la concentración de glucosa sanguínea a la dosis de 2,0 g/kg (<120 mg/dL). Los análisis estructurales se realizaron mediante pruebas cromatográficas, espectroscópicas, espectrométricas y químicas. Del estudio se aislaron e identificaron los siguientes compuestos: nandecilato de metilo (C20O2H40); behenato de metilo (C23O2H46) hexacosanoato de metilo(C27O2H54), así como 18-metoxicarbonil-3,4-didehidroibogamina, el flavonoides 5,7,3´-trihydroxi-3,6,4´-trimetoxiflavona, los cuales son reportados por primera vez en los análisis fitoquímicos para O. basilicum.Conclusión:estos hallazgos sustentan el potencial uso de la albahaca como alternativa considerable en el tratamiento hipoglucemiante.

AbstractBackground:Basil (Ocium basilicum) is an herb belonging to the family laminaceae, characterized by its medicinal benefits. Its use has been referred for the treatment of cancer, vitiligo, hypercholesterolemia, and diabetes mellitus.Objective:to evaluate the hypoglycemic effect of the methanol extract of basil, isolation and purification of its main compounds.Methods:The leaves and stems were collected in the sector La Hechicera, Mérida, Venezuela State. Samples were macerated in 20L of methanol to 70% v/v, dosing to increaseddoses between 1.0 and2.0 g/kg, using as experimental model, male rats of the C57BL/6 strain with hyperglycemia induced with alloxan monohydrate. A positivecontrol was included using as a hypoglycemic agent sitagliptin (400μg/kg). The extract was submitted to fractionation by open column chromatography,, whose fractions (175 ml each) were partnered by structural similarity and were dosed to the population under study. Serial blood samples from the base of the tail vein were obtained and were processed using the method of the glucose oxidase-peroxidase.Results:they showed a decrease of the concentration of blood glucose at a dose of 2.0 g/kg (< 120 mg/dL). Structural analyses were conducted using chromatographic, spectroscopic, spectrometric and chemical tests. They were isolated from the study and the following compounds were identified: nandecilato of methyl (C20O2H40); methyl behenate (C23O2H46), methyl hexacosanoate (C27O2H54) as well as 18-methoxycarbonyl-3, 4-didehidroibogamina, 5,7,3´-trihydroxi-3,6,4´- trimetoxiflavona flavonoid, which are reported for the first time in the phytochemical analysis for O. basilicum.Conclusion:These findings support the potential use of Basil as a weed of traditional medicine in the hypoglycemic treatment.

Features of the metabolic syndrome in the Berlin Fat Mouse as a model for human obesity.

BACKGROUND: The Berlin Fat Mouse BFMI860 is a polygenic obesity mouse model which harbors a natural major gene defect resulting in early onset of obesity. To elucidate adult bodily responses in BFMI860 mice that develop juvenile obesity, we studied features of the metabolic syndrome at 20 weeks. METHODS: We examined fat deposition patterns, adipokines, lipid profiles in serum, glucose homeostasis, and insulin sensitivity in mice that were fed either a standard maintenance (SMD) or a high-fat diet (HFD). RESULTS: Like many obese humans, BFMI860 mice showed hyperleptinemia accompanied by hypoadiponectinemia already at SMD that was further unbalanced as a result of HFD. Furthermore, BFMI860 mice had high triglyceride concentrations. However, triglyceride clearance after an oral oil gavage was impaired on SMD but improved on HFD. The oral and intraperitoneal glucose as well as the insulin tolerance tests provided evidence for reduced insulin sensitivity under SMD and insulin resistance on HFD. BFMI860 mice can maintain normal glucose clearance over a wide range of feeding conditions according to an adaptation via increasing the insulin concentrations. CONCLUSIONS: BFMI860 mice show obesity, dyslipidemia, and insulin resistance as three major components of the metabolic syndrome. As these mice develop the described phenotype as a result of a major gene defect, they are a unique model for the investigation of genetic and pathophysiological mechanisms underlying the observed features of the metabolic syndrome and to search for potential strategies to revert the adverse effects under controlled conditions.

Serum concentrations of resistin-like molecules beta and gamma are elevated in high-fat-fed and obese db/db mice, with increased production in the intestinal tract and bone marrow.

AIMS/HYPOTHESIS: Resistin and the resistin-like molecules (RELMs) comprise a novel class of cysteine-rich proteins. Among the RELMs, RELMbeta and RELMgamma are produced in non-adipocyte tissues, but the regulation of their expression and their physiological roles are largely unknown. We investigated in mice the tissue distribution and dimer formation of RELMbeta and RELMgamma and then examined whether their serum concentrations and tissue expression levels are related to insulin resistance. METHODS: Specific antibodies against RELMbeta and RELMgamma were generated. Dimer formation was examined using COS cells and the colon. RELMbeta and RELMgamma tissue localisation and expression levels were analysed by an RNase protection assay, immunoblotting and immunohistochemical study. Serum concentrations in high-fat-fed and db/db mice were also measured using the specific antibodies. RESULTS: The intestinal tract produces RELMbeta and RELMgamma, and colonic epithelial cells in particular express both RELMbeta and RELMgamma. In addition, RELMbeta and RELMgamma were shown to form a homodimer and a heterodimer with each other, in an overexpression system using cultured cells, and in mouse colon and serum. Serum RELMbeta and RELMgamma levels in high-fat-fed mice were markedly higher than those in mice fed normal chow. Serum RELMbeta and RELMgamma concentrations were also clearly higher in db/db mice than in lean littermates. Tissue expression levels revealed that elevated serum concentrations of RELMbeta and RELMgamma are attributable to increased production in the colon and bone marrow. CONCLUSIONS/INTERPRETATION: RELMbeta and RELMgamma form homo/heterodimers, which are secreted into the circulation. Serum concentrations of RELMbeta and RELMgamma may be a novel intestinal-tract-mediating regulator of insulin sensitivity, possibly involved in insulin resistance induced by obesity and a high-fat diet.