Influence of acute and chronic administration of benzylamine on glucose tolerance in diabetic and obese mice fed on very high-fat diet

The combination of vanadate plus benzylamine has been reported to stimulate glucose transport in rodent adipocytes and to mimic other insulin actions in diverse studies. However, benzylamine alone activates glucose uptake in human fat cells and increases glucose tolerance in rabbits. The aim of this work was to unravel the benzylamine antihyperglycemic action and to test whether its chronic oral administration could restore the defective glucose handling of mice rendered slightly obese and diabetic by very high-fat diet (VHFD). When VHFD mice were i.p. injected with benzylamine at 0.7 to 700 micromol/kg before glucose tolerance test, they exhibited reduced hyperglycemic response without alteration of insulin secretion. Whole body glucose turnover, as assessed by the glucose isotopic dilution technique, was unchanged in mice perfused with benzylamine (total dose of 75 micromol/kg). However, their in vivo glycogen synthesis rate was increased. Benzylamine appeared therefore to directly facilitate glucose utilisation in peripheral tissues. When given chronically at 2000 or 4000 micromol/kg/d in drinking water, benzylamine elicited a slight reduction of water consumption but did not change body weight or adiposity and did not modify oxidative stress markers. Benzylamine treatment improved glucose tolerance but failed to normalize the elevated glucose fasting plasma levels of VHFD mice. There was no influence of benzylamine ingestion on lipolytic activity, basal and insulin-stimulated glucose uptake, and on inflammatory adipokine expression in adipocytes. The improvement of glucose tolerance and the lack of adverse effects on adipocyte metabolism, reported here in VHFD mice allow to consider orally given benzylamine as a potential antidiabetic strategy which deserves to be further studied in other diabetic models.     

The glucose tolerance, insulin response and pancreatic exocrine function in patients after acute pancreatitis

In 25 patients having a history of acute pancreatitis (AP) in anamnesis one year ago and in 12 control subjects the insulin response to oral glucose was investigated and in some cases the exocrine function of pancreas was evaluated. The disturbances in glucose tolerance occurred in about 30% of the patients and were associated with impairment of insulin response and deterioration of exocrine pancreatic function. The double cortisone and glucose load did not influence the glucose tolerance in the patients. In persons investigated during AP and one year later only slight improvement of insulin response was noted. The results support the significance of follow-up studies of carbohydrate tolerance and insulin response in patients after AP for the evaluation of the diabetic risk in such cases.     

Continuous glucose monitoring in cystic fibrosis patients according to the glucose tolerance.

Cystic fibrosis (CF) is associated with a long preclinical state of abnormal glucose tolerance. The aim of this study was (i) to evaluate the profile of glucose tolerance in young adults with CF and (ii) to compare these results with those obtained by a continuous subcutaneous glucose monitoring (CGMS). CF subjects with fasting glycemia inferior to 126 mg/dl were included in the study. An oral glucose tolerance test (OGTT) identified the subjects either with a normal glucose tolerance (NGT), or impaired glucose tolerance (IGT), or diabetes. CGMS (Medtronic) was performed during 3 days to analyze mean glucose level, high glucose excursions, and glucose area under the curve (AUC). Forty-nine patients were included in the study. NGT (n=22), IGT (n=17), and diabetes groups (n=10) were comparable except with regard to age and BMI (p<0.001). HbA1c values in diabetes group were significantly higher (p<0.001) than in NGT and IGT groups. CGMS revealed peaks of glucose values superior to 200 mg/dl at least once after a meal in 8 patients (36%) with NGT, in 9 patients (52%) with IGT, and in all patients with diabetes (p<0.01). Mean CGMS glucose and glucose AUC values increased in patients with diabetes compared to patients with NGT and IGT (p<0.05). Peak of CGMS glucose reached 182+/-60 mg/dl in NGT group despite the normal glucose profile at OGTT. In conclusion, CGMS revealed pathological glucose excursions not only in patients with impaired glucose tolerance at OGTT but also in patients with a normal glycemic profile. CGMS could be a useful tool for the early detection of hyperglycemia in patients with CF.     

Chlorogenic acid reduces the plasma glucose peak in the oral glucose tolerance test: effects on hepatic glucose release and glycaemia

The effects of chlorogenic acid (CA) on hepatic glucose output, blood glucose levels and on glucose tolerance were analysed. Hepatic uptake of CA and its effects on hepatic catabolism of L-alanine and glucose-6-phosphatase (G-6-Pase) activity were also evaluated. CA (1 mM) inhibited about 40% of G-6-Pase activity (p < 0.05) in the microsomal fraction of hepatocytes, but no effect was observed on production of glucose from gluconeogenesis or on L-alanine catabolism, at various concentrations of CA (0.33, 0.5 and 1 mM), in liver perfusion experiments. Since there were indications of a lack of uptake of CA by the liver, it is possible that this compound did not reach sufficiently high intracellular levels to inhibit the target enzyme. Accordingly, intravenous administration of CA also failed to provoke a reduction in blood glucose levels. However, CA did promote a significant reduction (p < 0.05) in the plasma glucose peak at 10 and 15 min during the oral glucose tolerance test, probably by attenuating intestinal glucose absorption, suggesting a possible role for it as a glycaemic index lowering agent and highlighting it as a compound of interest for reducing the risk of developing type 2 diabetes.     

Effects of coffee consumption on glucose tolerance, serum glucose and insulin levels--a cross-sectional analysis.

OBJECTIVE: Coffee has several metabolic effects that could reduce the risk of type 2 diabetes. Our objective was to examine the effects of coffee consumption on glucose tolerance, glucose and insulin levels. RESEARCH DESIGN AND METHODS: A subsample of subjects aged 45 to 64 years in 1987 and in 1992 from the population-based FINRISK study (12,287 individuals) was invited to receive the standard oral glucose tolerance test at baseline. Plasma samples were taken after an overnight fast, and a two-hour oral glucose tolerance test was administered. Fasting and two-hour plasma glucose and insulin were measured in 2434 subjects with data on coffee use and potential confounders. RESULTS: After adjustment for potential confounding factors (age, body mass index, systolic blood pressure, occupational, commuting and leisure time physical activity, alcohol and tea drinking, smoking), coffee consumption was significantly and inversely associated with fasting glucose, two-hour plasma glucose, and fasting insulin in both men and women. Coffee consumption was significantly and inversely associated with impaired fasting glucose, impaired glucose regulation, and hyperinsulinemia among both men and women and with isolated impaired glucose tolerance among women. CONCLUSIONS: In this cross-sectional analysis, coffee showed positive effects on several glycemia markers.     

Influence of oral glucose load upon blood glucose level in relation to the time of day

Blood glucose levels were estimated at different times of day in fasted rats and after 30, 60,90 and 120 min, since oral glucose load. Circadian variations in basal glucose levels and in the levels after glucose load were observed with the highest values noted between 11 a.m. and 7 p.m., and the lowest ones about midnight. These variations were most prominent when the measurements were performed 60 min after glucose load. Circadian variation in glucose tolerance was also revealed with the best tolerance at about midnight while the worst one was noted at noon and in the afternoon.     

Seasonal variations in plasma glucose and insulin concentrations after glucose loading in the edible dormouse (Glis glis L.).

Glucose tolerance tests made in the Edible dormouse showed annual variations in B cell secretory capacity, associated with glucose tolerance changes. 1. During autumn and winter, the B cell is sensitive to glucose, and insulin regulates the high peripheral consumption of this hexose. 2. At the beginning of spring, insulin secretion decreases and glucose tolerance is impaired. In June, the B cell response si low or absent and a poor tolerance to glucose still persists. 3. The variations in B cell activity can be related to changing energy requirements during the year.     

Carbohydrate metabolism in pregnancy. Part II. Relation between maternal glucose tolerance and glucose metabolism in the newborn.

The objective of clinical management of the pregnant diabetic woman is to prevent the serious adverse effects of an abnormal glucose environment on the fetus. Neonatal glucose assimilation and insulin release over the first two hours of life were correlated with various indices of maternal carbohydrate metabolism in the third trimester. Of the 31 mothers studied 21 were defined as normal and 10 as having chemical diabetes. Neontal glucose assimilation during the first two hours of life correlated strongly with functions of both maternal glucose tolerance and mean diurnal glucose level, the strongest correlation being with the area under the three-hour oral glucose tolerance curve (P less than 0.001), Two-hour neonatal plasma glucose values of under 1.7 mmol/1 (30 mg/100 ml) were found only in the newborn of women whose glucose tolerance area measured over 41.6 area units (750 traditional units); thus, even in the borderline diabetic range glucose tolerance testing during the last trimester of pregnancy may be valuable in predicting likelihood of neonatal hypoglycaemia. The findings also shed light on the possible sensitizing role of mild maternal hyperglycaemia on fetal insulin production and secretion.     

The relation between free fatty acid levels and tolerance for glucose in a triple glucose tolerance test

The improved glucose tolerance observed in a multiple glucose tolerance test (Staub-Traugott effect) has been observed in dogs with concomitant measurement of immunoreactive insulin (IRI) and plasma free fatty acid (FFA). It was possible to reduce and in one experiment eliminate the improved glucose tolerance observed in the Staub-Traugott procedure. This was done in successive experiments in which the glucose challenge dose was 1 × BW^{0 period; 7} grams: (1) by injecting octanoate (0.1 mmoles/kg each hour) at the same time as the glucose; (2) by supplementing the injections with the infusion of octanoate (0.1 mmoles/kg/15 mins) during the second and third hours; (3) by repeating this last procedure after a seven day fast. Similar experiments were carried out with a larger glucose challenge dose (1 g/kg).Glucose tolerance appeared to depend as strongly on FFA levels as it did on IRI levels, and improvement in glucose tolerance occurred only when there was an associated reduction in FFA for a given glucose challenge. A measure of the Staub-Traugott effect was defined in terms of the different glucose utilizations during a multiple glucose tolerance test. An increase in the mean FFA levels achieved before or during a multiple glucose tolerance test lessened or eliminated the Staub-Traugott effect.     

The prognostic value of different glucose abnormalities in patients with acute myocardial infarction treated invasively

ABSTRACT: BACKGROUND: Diabetes (DM) deteriorates the prognosis in patients with coronary heart disease. However, the prognostic value of different glucose abnormalities (GA) other than DM in subjects with acute myocardial infarction (AMI) treated invasively remains unclear. AIMS: To assess the incidence and impact of GA on clinical outcomes in AMI patients treated with percutaneous coronary intervention (PCI). METHODS: A single-center, prospective registry encompassed 2733 consecutive AMI subjects treated with PCI. In all in-hospital survivors (n = 2527, 92.5 %) without the history of DM diagnosed before or during index hospitalization standard oral glucose tolerance test (OGTT) was performed during stable condition before hospital discharge and interpreted according to WHO criteria. The mean follow-up period was 37.5 months. RESULTS: The incidence of GA was as follows: impaired fasting glycaemia - IFG (n = 376, 15 %); impaired glucose tolerance - IGT (n = 560, 22 %); DM (n = 425, 17 %); new onset DM (n = 384, 15 %); and normal glucose tolerance NGT (n = 782, 31 %). During the long-term follow-up, death rate events for previously known DM, new onset DM and IGT were significantly more frequent than those for IFG and NGT (12.3; 9.6 and 9.4 vs. 5.6 and 6.4 %, respectively, P < 0.05). The strongest and common independent predictors of death in GA patients were glomerular filtration rate < 60 ml/min/1,73 m^2 (HR 2.0 and 2.8) and left ventricle ejection fraction < 35 % (HR 2.5 and 1.8, all P < 0.05) respectively. CONCLUSIONS: Glucose abnormalities are very common in AMI patients. DM, new onset DM and IGT increase remote mortality. Impaired glucose tolerance bears similar long-term prognosis as diabetes.     

Diagnosis of diabetes mellitus and disorders of glucose tolerance in patients after acute pancreatitis

The study aimed at evaluating an incidence of diabetes mellitus and carbohydrate tolerance disorders as well as insulinemia in patients with the history of the acute pancreatitis. Baseline glycemia was determined in 50 patients with a history of the acute pancreatitis and in 15 healthy individuals (aged between 18 and 65 years). Blood sugar was then determined 30, 60, 90 and 180 minutes following loading with 75 g of glucose. Fasting insulinemia and that following loading with 75 g glucose were determined at the same time period. Diabetes mellitus was diagnosed in 6 patients (12%) whereas carbohydrate tolerance in 4 patients (8%). A decrease in insulin response to carbohydrates was noted in 36 patients (72%) with a history of the acute pancreatitis in comparison with the control group. The obtained results suggest that the acute pancreatitis significantly decreases endocrine functioning of the pancreas. Therefore, metabolism of carbohydrates should be checked particularly in the individuals with a history of the acute pancreatitis without the symptoms of both diabetes mellitus and sugar tolerance disorders but with the signs of decreased insulin response to carbohydrates.     

Evaluating the glucose tolerance test in mice

The objective of this study was to determine the optimal conditions under which to assess glucose tolerance in chow- and high-fat-fed C57BL/6J mice. Mice were fed either chow or high-fat diet for 8 wk. Variables tested were fasting duration (0-, 3-, 6-, and 24-h and overnight fasting), route of administration (intraperitoneal vs. oral) load of glucose given (2, 1, or 0.5 g/kg and fixed 50-mg dose), and state of consciousness. Basal glucose concentrations were increased in high-fat- compared with chow-fed mice following 6 h of fasting (9.1 +/- 0.3 vs. 7.9 +/- 0.4 mmol/l P = 0.01). Glucose tolerance was most different and therefore significant (P = 0.001) in high-fat-fed mice after 6 h of fasting (1,973 +/- 96 vs. 1,248 +/- 83 mmol.l(-1).120 min(-1)). The difference in glucose tolerance was greater following an OGTT (142%), in contrast to an IPGTT, with a 127% difference between high fat and chow. We also found that administering 2 g/kg of glucose resulted in a greater level of significance (P = 0.0008) in glucose intolerance in high-fat- compared with chow-fed mice. A fixed dose of 50 mg glucose regardless of body weight was enough to show glucose intolerance in high-fat- vs. chow-fed mice. Finally, high-fat-fed mice showed glucose intolerance compared with their chow-fed counterparts whether they were tested under conscious or anesthetized conditions. We conclude that 2 g/kg glucose administered orally following 6 h of fasting is best to assess glucose tolerance in mice under these conditions.     

Comparison between the oral glucose tolerance test and the glucose infusion test in the characterization of protodiabetes]

Within 3 days the 2-hour glucose infusion test (GIT) and the 50gm oral glucose tolerance test (oGTT) were performed in 113 normal weight and 33 obese persons suspected to protodiabetes and in 14 control subjects respectively. The results are compared with criteria from a group of healthy persons without any heredity of diabetes worked out in our laboratory. In about 66 per cent of the investigated subjects a concordance between both tests could observed in carbohydrate tolerance. Abnormal results were found more frequently after the oral glucose application. From these finding it was concluded a higher sensitivity of the oGTT. On the other hand followup studies of the disagreed diagnosis have shown that in 91 per cent the test results of the GIT were reproduced. The insulin secretion pattern agreed in 70 per cent between both tests. Whereas the insulin secretion pattern during the oGTT does not allowed to differ between the groups using the glucose infusion test we were able to observe a significant diminished hormone release in the initial as well as in the late phases, if the carbohydrate tolerance was pathologically. Summarizing the results we concluded that the GIT is characterized by a good reproducibility and a higher diagnostic importance than the 50 gm oGTT.     

Normalization effect of preceding protein meals on “diabetic” oral glucose tolerance in Eskimos

Routine testing of 76 clinically non-diabetic Eskimos showed marked impairment of oral glucose tolerance in 54% but normal intravenous glucose tolerance in most of these.Total insulin output following the glucose drink was not found different in Eskimos with normal and abnormal glucose tolerance nor did lean meat meals given 60 minutes before the glucose significantly increase it.Intolerance to oral glucose loads appeared significantly related to a delay of insulin release and both timing of insulin response and shape of blood glucose curve normalized in the meat-preceded tests.     

The effect of prior exercise on oral glucose tolerance in late gestational women

Glucose tolerance deteriorates over the course of a normal human pregnancy as a result of increased peripheral insulin resistance. In contrast, physical exercise has been shown to improve glucose tolerance and blunt the insulin response to a glucose load in insulin-resistant individuals. The purpose of this study was to determine the effect of exercise on glucose tolerance and the insulin response in healthy women during the third trimester of pregnancy (33 weeks of gestation). Five subjects underwent oral glucose tolerance tests (a) 30 min following a 30-min exercise bout on a cycle ergometer at a relative intensity of 50% maximal aerobic capacity, and (b) on a control day without prior exercise. The area under the glucose concentration curve was not different between trials, while the area under the insulin concentration curve was decreased by 23% in the exercise trial compared with the control trial (P less than 0.05). These results suggest that the insulin response to a glucose load is improved in late gestational women by a single bout of moderate intensity exercise.     

Effects of isoflurane anesthesia on glucose tolerance and insulin secretion in Yucatan minipigs.

Isoflurane's effect on intravenous glucose tolerance and insulin secretion was studied in six Yucatan minipigs. Unanesthetized animals, with previously placed indwelling venous catheters, were tested while resting comfortably in slings. The same animals were then retested during isoflurane anesthesia. Serum glucose and insulin concentrations were measured at predetermined times in response to an intravenous bolus of dextrose. The glucose disappearance rate (k), baseline plasma insulin concentration, the area under the insulin response curve, and the insulinogenic index were significantly lower in the anesthetized animals than in controls. The results of this study indicate that anesthesia with isoflurane significantly alters the glucose/insulin response to an intravenous glucose tolerance test and, therefore, is unsuitable for studies when glucose tolerance is to be assessed.     

Effects of exogenous growth hormone on insulin action and glucose metabolism in the dwarf 'little' mouse

The in vivo actions of growth hormone (GH) on insulin activity and glucose homeostasis were examined in the GH-deficient Little mouse. The insulin-like action of GH was revealed during glucose tolerance tests on the animals after acute treatment with the hormone and the insulin-antagonistic action was demonstrated in both glucose tolerance tests and insulin tolerance tests on the mice after chronic GH infusion. The primary mechanism of the GH actions is to influence the responses of the target tissues to circulating insulin in vivo. The pancreatic function seems to be of little importance in the alteration of glucose metabolism after acute exposure to GH as no significant change of the levels of plasma insulin was detected. It is concluded that the GH-deficient Little mouse is an ideal laboratory model for the elucidation of the molecular mechanism of the interaction between insulin and GH in the regulation of carbohydrate metabolism.     

Plasma insulin and C-peptide responses to oral glucose load after physical exercise in men with normal and impaired glucose tolerance

Blood glucose, plasma insulin and C-peptide responses to oral glucose tolerance test (OGTT) were studied under basal conditions and immediately after 90-min exercise (60% VO2 max) in nondiabetic subjects with normal or impaired glucose tolerance. During the postexercise recovery blood glucose response to OGTT was increased in normal subjects and markedly decreased in those with impaired glucose tolerance, while insulin and C-peptide responses were diminished in both subgroups. The ratio of blood glucose to insulin was similarly elevated in all subjects. Comparing with basal conditions no significant changes were found in C-peptide to insulin ratio in response to OGTT after exercise, although a tendency towards an elevation of this ratio was noted in the subjects with impaired glucose tolerance. The data indicate that the reduced insulin response to OGTT during postexercise recovery in healthy subjects is due to diminished insulin secretion without any substantial changes in the hormone removal from blood, whereas in the glucose intolerant men the latter process may be enhanced.     

Energy balance and diabetes. The effects of cold exposure, exercise training, and diet composition on glucose tolerance and glucose metabolism in rat peripheral tissues

The effects of cold exposure, exercise training, and diet (high fat versus high carbohydrate) on glucose tolerance and glucose metabolism in rat peripheral tissues will be briefly reviewed. Stimulation of energy expenditure by cold exposure (4 degrees C) or exercise training generally leads to decreased plasma insulin levels and to an improvement in glucose tolerance, suggesting that insulin action on peripheral tissues is increased when energy expenditure is stimulated. On the contrary, feeding high-fat diets to sedentary rats living in the warm (25 degrees C) induces hyperinsulinemia and insulin resistance resulting in a marked deterioration of glucose tolerance. Nevertheless, cold exposure reverses the diabetogenic effects of high-fat feeding, demonstrating that nutrition-induced insulin resistance is amplified in sedentary animals living at temperatures close to thermoneutrality. Radioactive tracer studies of 2-deoxyglucose uptake in peripheral tissues revealed that cold exposure synergistically potentiates the effects of insulin on glucose uptake in skeletal muscles as well as in white and brown adipose tissues. However, more recent data showed that cold exposure improves glucose tolerance and stimulates glucose uptake in starved animals (ie., in the virtual absence of circulating insulin) nearly by the same order of magnitude as in fed animals. It is therefore concluded that cold exposure, and possibly also exercise, improve glucose tolerance and stimulate glucose uptake in peripheral tissues primarily by enhancing glucose oxidation via insulin-independent pathways, and secondarily by increasing the responsiveness of peripheral tissues to insulin.     

Studies on oral glucose intolerance in fish

The oral glucose tolerance test, a diagnostic procedure used in the detection of human diabetes, was used to study carbohydrate metabolism in rainbow trout, Salmo gairdneri (Richardson). Fish exhibited pronounced and persistent hyperglycaemia on oral glucose administration. Hyperglycaemia was accompanied by decrease in blood amino acids, serum free fatty acids and cholesterol and marked increase in hepatic storage of glycogen. The incidence of oral glucose intolerance results, at least in part from insufficient circulating insulin. Exogenous insulin exerts a hypoglycaemic action and effectively abolishes the hyperglycaemia resulting from glucose administration. Tolbutamidc, the sulphonylurea hypoglycaemic drug, is without effect. Possibly as an indirect result of hyperadreno-corticism, oral glucose tolerance is markedly improved in the pre-spawning female. Long-term feeding of high carbohydrate diet to goldfish Carassius auratus (L.) resulted in gross hepatomegaly due to excessive hepatic glycogen accumulation and, possibly, fatty change of the liver. Protein metabolism was impaired as evidenced by protein depletion. Such degenerative changes in liver metabolism are probably a direct result of oral glucose intolerance and reflect a metabolism adapted to diets normally low in available carbohydrate.