Oral Glucose Overload Research Articles

Aerobic interval exercise improves parameters of nonalcoholic fatty liver disease (NAFLD) and other alterations of metabolic syndrome in obese Zucker rats

Metabolic syndrome (MS) is a group of metabolic alterations that increase the susceptibility to cardiovascular disease and type 2 diabetes. Nonalcoholic fatty liver disease has been described as the liver manifestation of MS. We aimed to test the beneficial effects of an aerobic interval training (AIT) protocol on different biochemical, microscopic, and functional liver alterations related to the MS in the experimental model of obese Zucker rat. Two groups of lean and obese animals (6 weeks old) followed a protocol of AIT (4 min at 65%-80% of maximal oxygen uptake, followed by 3 min at 50%-65% of maximal oxygen uptake for 45-60 min, 5 days/week, 8 weeks of experimental period), whereas 2 control groups remained sedentary. Obese rats had higher food intake and body weight (P < 0.0001) and suffered significant alterations in plasma lipid profile, area under the curve after oral glucose overload (P < 0.0001), liver histology and functionality, and antioxidant status. The AIT protocol reduced the severity of alterations related to glucose and lipid metabolism and increased the liver protein expression of PPARγ, as well as the gene expression of glutathione peroxidase 4 (P < 0.001). The training protocol also showed significant effects on the activity of hepatic antioxidant enzymes, although this action was greatly influenced by rat phenotype. The present data suggest that AIT protocol is a feasible strategy to improve some of the plasma and liver alterations featured by the MS.

Hiperglicemias durante el embarazo

Entre los meses de junio a setiembre de 1991, se eligieron al azar 50 gestantes en el tercer trimestre de embarazo con la finalidad de evaluar los niveles de glicemia. Todas fueron pacientes hospitalizadas por complicaciones médicas, obstétricas o en inicio de trabajo de parto. Siguiendo las recomendaciones de la Segunda Conferencia Internacional sobre Diabetes Mellitus Gestacional, las gestantes fueron sometidas a la prueba de una hora con sobrecarga oral de glucosa y se consideró hipoglicemia durante el embarazo cuando el valor de la glucosa plasmática fue mayor o igual a 130 mg/dl. La edad materna promedio fue de 24.7 +/- 7.1 años con rango de 14 a 40 años. De las 50 gestantes, 24 (48%) tenían antecedentes de riesgo para Diabetes Mellitus Gestacional y 26 (52%) no. No se encontró diferencia significativa en la incidencia de Hiperglicemia entre estos dos grupos. Tampoco se encontró correlación entre la edad materna y los valores de glucosa en cada uno de los grupos. En la muestra estudiada, 50 gestantes, se encontró un caso manifiesto de Hiperglicemia en el grupo con riesgo y un caso en el grupo sin riesgo; estos dos casos representan una incidencia total de 4% de Diabetes Gestacional.

Menstrual Cycle Alterations during Adolescence: Early Expression of Metabolic Syndrome and Polycystic Ovary Syndrome

Study ObjectiveTo assess the importance of the menstrual pattern as a marker for clinical and laboratory alterations related to metabolic syndrome (MS) and polycystic ovary syndrome (PCOS) among Brazilian adolescents. DesignA cross-sectional study. SettingEndocrine Gynecology Outpatient Clinic of the Adolescent Health Studies Center (NESA) at the Pedro Ernesto University Hospital. Participants59 girls (12-19 years old) were classified by their menstrual cycles as regular (n = 23) and irregular (n = 36). InterventionNone. Main Outcome MeasuresBiochemical collections were made of peripheral blood after fasting for 12 hours, and the oral glucose tolerance test with 75 g of anhydrous glucose. ResultsPCOS, MS, and the criteria for MS were significantly more frequent (P < .05) in the subgroup with irregular menstruation. Adolescents with irregular cycles presented a significant increase in waist circumference, glycemia 2 hours after oral glucose overload (2 h), fasting and 2-h insulin, HOMA-IR, and triglycerides. In contrast, the glucose/insulin ratio, quantitative insulin-sensitivity check index, and HDL serum levels were significantly lower among patients with irregular menstruation, compared to those with regular cycles. In the logistic regression, we noted that insulin 2 h ≥ 75 μIU/mL (r = 1.90; P = .018), waist circumference > 95 cm (r = 2.21; P = .006) and diagnosis of PCOS (r = 1.93; P = .023) were significantly correlated to irregular cycles. ConclusionsWe concluded that close observation of menstrual cycle patterns is an important tool for identifying adolescents at higher risk of developing PCOS and MS.

Two-hour insulinemia after oral glucose overload and women at risk of pregnancy-induced hypertensive disorders

Objective: Pregnant women with impaired insulin sensitivity are at risk for developing pregnancy-induced hypertensive disorders (PIHD). We analyzed glucose and insulin circulating levels throughout a 2-h oral 75 g glucose tolerance test in pregnant women, and related the 2-h insulinemias to PIHD prevalence. Methods: Pregnant women (gestational week 24–28) were submitted to a glucose overload, and glucose and insulin plasma concentrations were measured throughout the test. These peripheral metabolite levels, the homeostasis model assessment (HOMA) values and the glucose to insulin ratio (G:Ir) were analyzed. Anthropometric parameters and pregnancy outcome were recorded. Results: Women with normal fasting glycemia, insulinemia and HOMA values, G:Ir and 2 h-glycemia but whose 2 h-insulinemia was higher than 215.25 pM were at greater risk for developing late pregnancy hypertension and preeclampsia compared to women of similar characteristics but whose 2 h-insulinemias were lower than 215.25 pM. Conclusion: 2-h insulinemias higher than 215.25 pM after a 75 g glucose overload could be highly indicative of women at increased risk of developing PIHD.

Relationship between glycated hemoglobin and glucose concentrations in the adult Galician population: selection of optimal glycated hemoglobin cut-off points as a diagnostic tool of diabetes mellitus

Aims/hypothesisTo analyze the relationship between glucose and glycated hemoglobin (HbA1c) in the adult Galician population, evaluate the use of HbA1c for the screening and diagnosis of diabetes, and calculate the diagnostic threshold required for this purpose. MethodsWe analyzed data on 2848 subjects (aged 18–85 years) drawn from a study undertaken in 2004 to assess the prevalence of diabetes in Galicia. For study purposes, diabetes was defined using the criteria recommended in 2002. Participants were classified into four glucose-based groups. The relationship between glucose and HbA1c was described using linear regression models, generalized additive models and Spearman's correlation. Diagnostic capacity was assessed, and optimal HbA1c cut-off points were calculated as a diabetes marker using the receiver operating characteristic curve. ResultsPrevalence of pre-diabetes, unknown diabetes and known diabetes was 20.86, 3.37 and 4.39%, respectively. The correlations between HbA1c and fasting glucose were higher than those obtained for HbA1c and glycemia at 2h of the oral glucose overload (0.344 and 0.270, respectively). Taking glucose levels as the gold standard, a greater discriminatory capacity was obtained for HbA1c (area under de cruve: 0.839, 95% confidence intervals: 0.788–0.890). Based on the study criteria, the optimal minimum and maximum HbA1c values were 5.9% and 6.7%, respectively. Conclusions/interpretationHbA1c did not prove superior to glycemia for diagnosis of diabetes in the adult Galician population, and cannot therefore be used to replace the oral glucose tolerance test for screening and diagnosis purposes. Indeed, determination of glucose is essential to verify the diagnosis in the majority of cases.

Nadir growth hormone after oral glucose overload in obese subjects

The nadir growth hormone (n-GH) in the oral glucose tolerance test (OGTT) is the gold standard for the demonstration of secretory autonomy of this hormone and a laboratory parameter necessary for the diagnosis of acromegaly (1,2). Although measurement of GH after oral glucose overload is not recommended during treatment with somatostatin analogs or GH receptor antagonists (3), normalization of n-GH continues to be necessary for the definition of “control” after surgical treatment of acromegaly (3). Nadir GH levels vary according to the assay used (4-7) and are influenced by gender, age and body mass index [BMI (4-6,8)]. The inverse correlation with BMI observed in normal subjects (4,6,8) and acromegalic patients (9) indicates the need for adjusting the n-GH cut-off as a function of BMI (4,6,8). We have previously defined n-GH reference values in subjects with a BMI ≤ 27 kg/m2 (5). The possibility that the current reference values are inadequate (overestimated) for obese subjects led to the elaboration of the present study, for which the objective was to evaluate the n-GH in the OGTT in subjects with a BMI ≥ 30 kg/m2. A total of 200 volunteers (120 women and 80 men) ranging in age from 18 to 70 years (median of 44 years), matched with 200 subjects from the previous study (5), who had a BMI ≥ 30 kg/m2 (median of 34.8 kg/m2) were studied. The selection criteria, protocol and statistical analysis are described in detail in the previous study (5). Briefly, apparently healthy subjects (excluding pregnant women) without associated diseases who were not using medications that might interfere with GH levels and who presented no abnormalities upon minimum laboratory assessment (glycemia, blood count, albumin, creatinine, TSH, GOT, GPT and bilirubin) were selected. The study was approved by the Ethics Committee of Santa Casa de Belo Horizonte. The GH Immulite kit (Diagnostic Products Corporation, Los Angeles, CA) was used for the measurement of GH since it is the kit most widely used in Brazil. In addition, the kit meets the requirements of calibrated standards against > 95% pure preparations of GH 22 kDa (10), its specificity for the 22 and 20 kDa isoforms is known (4), and its intraand interassay sensitivity and variability have been previously established (5,11). The cut-off was defined as the 97.5th percentile of the values found. The Spearman correlation test was used to analyze the correlation between n-GH and age, BMI. The nonparametric Kruskal-Wallis test and the parametric Shapiro-Wilk test were used to compare GH values obtained between groups. P values 35 years (n = 80), with higher values in the former (n-GH cut-off: 0.42 μg/L versus 0.3 μg/L, p < 0.05). There was an inverse correlation between n-GH levels and 1 Programa de Pos-graduacao, Santa Casa de Belo Horizonte, MG, Brazil 2 Faculdade de Medicina do Vale do Aco, Ipatinga, MG, Brazil

El ácido úrico es un predictor de desarrollo de diabetes mellitus tipo 2 en la población general

Abnormal uric acid levels are considered by some to be a risk factor for metabolic disorders, whereas others consider it to be just a marker. We therefore examined the association between plasma uric acid concentrations and the risk of type 2 diabetes mellitus. We undertook a prospective, 8-year study of 411 persons from the general population with no carbohydrate metabolism disorder at the start of the study evaluated by oral glucose overload. The following variables were measured at the beginning and end of the study: uric acid, triglycerides, cholesterol, high-density lipoprotein cholesterol, glucose and insulin in plasma, body mass index and waist-to-hip ratio. The participants were classified according to their plasma uric acid concentration, with a cut-off at the 33rd percentile (men, 291.45 and women, 208.18 micromol/l). Participants with plasma uric acid concentrations above the 33rd percentile at the start of the study had worse lipid and anthropometric profiles. These persons were at greater risk for carbohydrate disorder at the end of the 8- year follow-up study (relative risk, 1.73; 95% confidence interval, 1.04-2.8). No significant differences were found in age or in the remaining variables studied between these two groups. Increased uric acid levels in response to a possible chronic increase in oxidative stress may predict future disorders or complications such as type 2 diabetes in otherwise healthy persons.

Nanoparticulate biopolymers deliver insulin orally eliciting pharmacological response

The aim of this study was to characterize and evaluate a novel oral insulin nanoparticulate system based on alginate‐dextran sulfate core, complexed with a chitosan‐polyethylene glycol‐albumin shell. Insulin‐loaded nanospheres (25, 50, 100 IU/kg) administered orally to diabetic rats reduced glycemia in a dose dependent manner. This effect lasted over 24 h with a maximal effect after 14 h. Nanospheres increased insulin plasma level and improved glycemic response to an oral glucose overload. After 4 days oral administration (50 IU/kg/day), the metabolic status of diabetic rats improved with a reduction in water intake, urine excretion and proteinuria. FITC‐insulin‐loaded nanospheres administered to an isolated intestinal loop were taken up by the intestinal mucosa. They strongly adhered to villus apical enterocytes and markedly labeled Peyer's patches. It is concluded that nanospheres preserve insulin and exert an antidiabetic effect after oral administration. This is explained by a protective effect against proteolytic enzymes by the albumin coating, by the mucoadhesive properties of chitosan‐polyethylene glycol, and by the possibility of chitosan reversibly altering tight junctions leading to an improved absorption of insulin. This formulation demonstrates beneficial effects on diabetic symptoms and will be of interest in the treatment of diabetes with oral insulin. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5290–5305, 2008

The effects of duodenal-jejunal exclusion on hormonal regulation of glucose metabolism in Goto-Kakizaki rats

Background The antidiabetic effect of bariatric surgery has been interpreted as a conceivable result of surgically induced weight loss and decreased caloric intake. However, glycemic control often occurs within days, before significant weight loss has been reached. The aim of our work was to investigate the hormones that control glycemic status in diabetes mellitus after a duodenal-jejunal exclusion in an animal model of nonobese type 2 diabetes. Methods Twelve (12- to 14-week-old) rats (Goto-Kakizaki) randomly underwent one of the following procedures: gastrojejunal bypass (group 1, n = 6) or no intervention (controls) (group 2, n = 6). Both groups were fed with the same type and amount of diet. At basal time (preoperative) and after intervention (1 week and 1 month), weight and fasting glycemia were measured. An oral glucose tolerance test (OGTT) was realized at same times. Hormone levels (insulin, glucagons-like petide 1 [GLP-1], glucose-dependent insulinotropic peptide [GIP], glucagon, and leptin) were measured after 20 minutes of oral glucose overload. Age-matched Goto-Kakizaki rats were used as controls for all variables. Results Rats in group 1 and group 2 remained with the same weight during the protocol. The OGTT showed an improvement in glycemic levels in group 1; glucose levels were better at 1 week and 1 month after the surgery in all times of OGTT (basal, 10 minutes, and 120 minutes). Basal glucose levels at time 0 in basal time, at 1 week, and at 1 month were lower in group 1 than group 2. Postoral glucose overload levels of glucagon, insulin, GLP-1, and GIP remained unchaged during the treatment in both groups. In group 1, leptin levels had a significant decrease at 1 week and 1 month after surgery (basal time (6.1 ± 1.6 ng/mL) versuss 1 week (0.9 ± 0.9 ng/mL) versus 1 month (0.7 ± 0.6 ng/mL) ( P < .05). Conclusion Gastrojejunal bypass in a nonobese diabetic model improves glycemic control with a significant decrease in leptin levels, without changes in enteroinsular axis (GLP-1, GIP, glucagons, and insulin levels).

Estudio del metabolismo hidrocarbonado en pacientes con obesidad mórbida: influencia de la pérdida de peso

Examination of carbohydrate metabolism derangements in patients with morbid obesity and the influence of weight reduction through nutritional intervention. Assessment of gender influence on carbohydrate metabolism derangements and on response to diet. 59 patients with morbid obesity were studied with anthropometric assessment and with carbohydrate metabolism assessment through an oral glucose overload and measurement of insulin resistance, before and after a dietary intervention alternating diets of very low caloric content with conventional low-calorie diets. A very significant global weight reduction in both sexes was observed (95% confidence interval [CI], 26.9 to 39.8 kg in males, and 13.5 to 20.3 kg in women). A significant improvement in basal blood glucose was found in both sexes (95% CI: males, 0.44 to 46.5 mg/dl; women, 9.5 to 32.8 mg/dl), and in 120 minute oral glucose tolerance test (OGTT) blood glucose in women (95% CI: 3.5 to 52.9 mg/dl). Both males and women showed significant improvement in basal insulinemia (95% CI: males, 1.6 to 14.2 microU/ml; women, 3.9 to 8.5 microU/ml) and in sex hormone-binding globulins (SHBG) (95% CI: males, -30.1 to -13.3 nmol/l; women, -54 to -19.4 nmol/l). Both males and women showed an improvement of sensitivity to insulin measured with HOMA (HOMAIR) (95% CI: males, 1.46 to 3.59; women, 0.67 to 2.24). In patients with morbid obesity carbohydrate metabolism derangements are common. Weight reduction led to a significant reduction of these derangements.

Diagnosticando la diabetes mellitus tipo 2: en atención primaria, con la glucemia basal y la hemoglobina glucosilada es suficiente

To determine the validity of glycosylated hemoglobin (HbA1c) values as a method to diagnose type 2 diabetes mellitus (DM2) in a population at risk seen in primary care. Cross-sectional analytical study. Data were obtained for the Raval Sud study population (epidemiologic study of alterations in glucose metabolism in a population at risk). 454 subjects from this population (mean age, 65 +/- 3 years; 52% male) at high risk for DM2, seen at a primary care center, were included in the study. We recorded demographic data and laboratory values for fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), and HbA1c. The diagnostic criteria used for DM2 were those published by the WHO in 1999. Values for HbA1c were expressed as the number of standard deviations (SD) above the mean. Levels of HbA1c correlated with FPG (r=0.72) and glucose levels 2 h after oral glucose overload (r=0.43). Thirty percent of the patients with FPG between 110 and 125 mg/dL had HbA1c values higher than the reference limits. A combined technique based on FPG>125 mg/dL or FPG 110-125 mg/dL with HbA1c > or = 3 SD (5.94%) showed a sensitivity of 92% and a specificity of 95%. When FPG is inconclusive (110-125 mg/dL), an HbA1c value more than 3 standard deviations above the mean (>5.94%) is useful in suggesting a likely diagnosis of diabetes and identifying patients who require treatment.

Clonazepam increases in vivo striatal extracellular glucose in diabetic rats after glucose overload

Hyperglycemia modulates brain function, including neuronal excitability, neurotransmitter release and behavioral changes. There may be connections between the GABAergic system, glucose sensing neurons and glucose in the neuronal environment that shed light on the mechanism by which GABA A agents influence depressive behavior in diabetic rats submitted to the forced swimming test. We aimed to investigate whether clonazepam (CNZ), a GABA A receptor positive modulator, modifies in vivo striatal extracellular glucose levels in diabetic rats under fasting condition or after oral glucose overload. Streptozotocin diabetic and nondiabetic rats were submitted to in vivo striatal microdialysis. Perfusate samples were collected at baseline, during fasting and following administration of CNZ (0.25 mg/kg) and oral glucose overload. Blood glucose and striatal extracellular glucose were measured simultaneously at several time points. Fasting striatal glucose levels were higher in diabetic than in nondiabetic rats and the differences between these animals were maintained after glucose overload. The increases in extracellular striatal glucose after glucose overload were around 40% and blood to brain transference was decreased in diabetics. CNZ treatment paradoxically increased striatal glucose after glucose overload in diabetic rats, which may mark the dysfunction in brain glucose homeostasis.

Discriminatory capacity of high-normal (110-140 mg/dl) value of plasma glucose at the end of an oral glucose overload test

Discriminatory capacity of high-normal (110-140 mg/dl) value of plasma glucose at the end of an oral glucose overload test

Prevalencia de diabetes mellitus e intolerancia a la glucosa en población entre 30 y 75 años en Asturias, España

To know the prevalence of type 2 diabetes mellitus (DM2) and glucose intolerance (GIT) in the adult population in Asturias. Population based, cross-sectional study. A total of 1,034 individuals (54,1%, women) aged 30-75 years were randomly selected. Individuals responded to a questionnaire, underwent physical examination, and an oral glucose overload test; vein blood was extracted to determine both basal and 2-hour glucose levels. The diagnostic criteria set up by the World Health Organization in 1985 were used. The overall DM2 prevalence was 9.9% (8.2% to 11.7%), known DM 4% (2.8% to 5.1%), unknown DM 5.9% (4.5% to 7.4%). The unknown diabetes/hnown diabetes ratio was 1.5/1. The prevalence of GIT was 13.3 % (11.3% to 15.2%). The prevalence of DM for the Segi population (30-64 years) was 8.2% among men and 5.2% among women. Factors independently associated with DM included age, increased blood pressure, family history of diabetes, obesity, and hypertriglyceridemia. The prevalence of DM2 in the adult population of Asturias (9.9%) is moderately high and similar to that observed in our country and other white populations in the world. More than half of patients with DM are unaware of their condition; thus, planning strategies for and early diagnosis would be helpful for the high risk populations.

Plasma insulin levels are increased by sertraline in rats under oral glucose overload.

Recognition and control of depression symptoms are important to increase patient compliance with treatment and to improve the quality of life of diabetic patients. Clinical studies indicate that selective serotonin reuptake inhibitors (SSRI) are better antidepressants for diabetic patients than other drugs. However, preclinical trials have demonstrated that not all SSRI reduce plasma glucose levels. In fact, fluoxetine increases and sertraline decreases glycemia in diabetic and non-diabetic rats. In the present study we evaluated plasma insulin levels during fasting and after glucose overload after treatment with sertraline. Adult male Wistar rats were fasted and treated with saline or 30 mg/kg sertraline and submitted or not to glucose overload (N = 10). Blood was collected and plasma insulin was measured. The mean insulin levels were: fasting group: 25.9 +/- 3.86, sertraline + fasting group: 31.10 +/- 2.48, overload group: 34.1 +/- 3.40, and overload + sertraline group: 43.73 +/- 5.14 microU/ml. Insulinemia was significantly increased in the overload + sertraline group. There were no differences between the other groups. No difference in glucose/insulin ratios could be detected between groups. The overload + sertraline group was the only one in which a significant number of individuals exceeded the upper confidence limit of insulin levels. This study demonstrates that sertraline increases glucose-stimulated insulin secretion without any change in peripheral insulin sensitivity.

Endocrine and metabolic abnormalities involved in obesity associated with typical antipsychotic drug administration.

In this study, the authors assessed the endocrine system and glucose tolerance in obese and non-obese women chronically treated with typical antipsychotic drugs (AP). In particular, we tested the hypotheses that these subjects display hypogonadism and increased insulin resistance compared to healthy weight-matched controls, as these abnormalities create a tendency towards excessive body weight gain. Twenty-six AP-treated women were matched with 26 healthy women by age, body mass index and day of the menstrual cycle. The following serum variables were evaluated in each subject: glucose tolerance after an oral glucose overload, insulin, leptin, beta-endorphin, reproductive hormones, adrenal steroids and lipids. Compared to controls, AP-treated women displayed significantly higher levels of basal glucose, insulin after 60 min of the glucose overload, prolactin, thyroid stimulating hormone and beta-endorphin, with lower levels of C-Peptide, progesterone, 17-OH progesterone, androstenedione and high-density lipoprotein cholesterol. The levels of estradiol, estrone and leptin did not differ between the groups. Thus, women treated with typical AP appeared to display more insulin resistance than healthy controls, predisposing them to excessive weight gain. Insulin sensitivity might be further impaired when the subject switches to atypical AP administration. Metformin and related agents may reduce body weight in these subjects. The high levels of the opiate beta-endorphin suggest that opiate antagonists such as naloxone and naltrexone might be useful as well. Even though the luteal phase of the menstrual cycle appears to be severely disturbed, the normal serum levels of estradiol and estrone do not support the proposal derived from animal experimental studies about the use of estrogens or tamoxifen to counteract AP-induced obesity.

Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats.

Diabetic patients have a 20% higher risk of depression than the general population. Treatment with antidepressant drugs can directly interfere with blood glucose levels or may interact with hypoglycemic agents. The treatment of depression in diabetic patients must take into account variations of glycemic levels at different times and a comparison of the available antidepressant agents is important. In the present study we evaluated the interference of antidepressants with blood glucose levels of diabetic and non-diabetic rats. In a first experiment, male adult Wistar rats were fasted for 12 h. Imipramine (5 mg/kg), moclobemide (30 mg/kg), clonazepam (0.25 mg/kg), fluoxetine (20 mg/kg) sertraline (30 mg/kg) or vehicle was administered. After 30 min, fasting glycemia was measured. An oral glucose overload of 1 ml of a 50% glucose solution was given to rats and blood glucose was determined after 30, 60 and 90 min. Imipramine and clonazepam did not change fasting or overload glycemia. Fluoxetine and moclobemide increased blood glucose at different times after the glucose overload. Sertraline neutralized the increase of glycemia induced by oral glucose overload. In the second experiment, non-diabetic and streptozotocin-induced diabetic rats were fasted, and the same procedures were followed for estimation of glucose tolerance 30 min after glucose overload. Again, sertraline neutralized the increase in glycemia after glucose overload both in diabetic and non-diabetic rats. These data raise the question of whether sertraline is the best choice for prolonged use for diabetic individuals, because of its antihyperglycemic effects. Clonazepam would be useful in cases with potential risk of hypoglycemia.

GABA Agonists Differentially Modify Blood Glucose Levels of Diabetic Rats

This study described the effects of GABA agonists on glucose plasma concentrations of streptozotocin-induced diabetic rats. Low doses of an indirect GABA agonist, AOAA (aminooxyacetic acid); a GABAA and a GABAB agent, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridone) and baclofen, respectively; and a benzodiazepine were administered to non-diabetic and to diabetic rats. Plasma glucose concentrations were estimated during fasting and after an oral glucose load. Diazepam (1 mg/kg), baclofen (1 mg/kg) and AOAA (30 mg/kg), significantly decreased glycemia after oral glucose overload of streptozotocin-induced diabetes. None of the GABA-acting agents tested changed fasting or glucose overload glycemia of normal rats. Diazepam was the only drug to increase the fasting blood glucose concentration of diabetic rats. Treatment with AOAA or diazepam was accompanied by increased insulin plasma concentrations in diabetic rats to levels similar to the ones of non-diabetic animals. These results demonstrate that benzodiazepines and other GABA drugs act the endocrine pancreas in vivo, ultimately increasing plasma insulin and decreasing high blood glucose levels of diabetic rats. The acute and prolonged effects of the multitude of drugs acting on the GABAA-benzodiazepine-chloride ionophore complex remain to be broadly investigated as a therapeutic tool in diabetes.

Increased serum N-acetyl-beta-D-glucosaminidase and alpha-D-mannosidase activities in obese subjects.

We have studied N-acetyl-beta-D-glucosaminidase and alpha-D-mannosidase activities in human sera from 35 control subjects, 47 normo- and hyperinsulinemic obese persons, and 12 diabetic patients after a fasting period of 12 h and at 30, 60, 90, and 120 min after an oral glucose overload. The results show a significantly higher activity of these 2 enzymes in obese subjects and diabetic patients, of similar magnitude, especially in those obese persons with a higher grade of obesity. Moreover, the activity of these glycosidases decreases in a similar way in all these 3 groups after the oral glucose overload.