Effect of the daily injection of tolbutamide into pregnant rats on the pancreatic insulin content of their offspring

The pancreas of pups born to rats injected daily with tolbutamide (75 mg/kg) throughout pregnancy contained significantly less insulin than those born to saline-injected rats. The difference was no longer statistically significant 5 days after birth. Intraperitoneal injection of the drug caused a transient fall in maternal and probably fetal blood glucose. At the concentration of 200 μg/ml, tolbutamide did not significantly influence insulin release by the rat fetal pancreas in vitro. The reduction of pancreatic insulin in the tolbutamide exposed pups may, therefore, be explained by decreased fetal blood sugar or alternatively by direct inhibition by tolbutamide of insulin synthesis by rat fetal B-cells. These and previous results lead us to question the so-called “B-cytotrophic” effect of sulfonylurea derivatives in normal rodents.     

Inhibition of sucrase by tris in rat and man,demonstrated by oral loading tests with sucrose

In the course of work concerned with the inhibition of small intestinal carbohydrate digesting enzymes, experiments were performed on rats and two healthy volunteers using tris as a sucrase inhibitor. The following results were obtained: (1) Tris does not lower the blood glucose in fasting rats after oral or subcutaneous doses up to 500 mg/kg, when administered as neutral solution (pH 7.0). (2) Tris reduces the glycemia in rats and human subjects after a sucrose load. In addition, the insulinemia caused by administration of sucrose is reduced in man. This smoothing effect on both curves is dose-dependent. A delay of gastric emptying by tris could be excluded. (3) After a glucose or maltose load in rats, tris has no effect on the blood sugar curve. (4) The marked smoothing effect of tris after sucrose loading is probably caused by its well-known in vitro inhibitory effect on intestinal sucrase activity of pigs and humans.     

Comparative evaluation of the hypoglycemic activity of the vegetal complex of Phaseolus vulgaris and chlorpropamide in experimental diabetes

Experiments on rabbits with alloxan diabetes showed that the plant complex (PC) reduced the level of glycemia after single administration for 6-8 h by 27-32%. A similar effect was demonstrated with chlorpropamide. However the PC produced a longer hypoglycemic effect. In course treatment the PC returned the blood level of glucose (5.14 +/- 0.62 mmol/l) to normal on the 11th day whereas with chlorpropamide this indicator was almost normal (6.6 +/- 1.1 mmol/l) on the 15th day only. A rapid decrease in the blood glucose concentration caused by the PC was observed in AIS induced hyperglycemia. The PC demonstrated its sugar reducing action by extrapancreatic means.     

Prostaglandins affect the central nervous system to produce hyperglycemia in rats

The influence of prostaglandins (PG) on central nervous system regulation of blood sugar homeostasis was studied in rats. Substances were injected into the third cerebral ventricle of anesthetized rats while rectal temperature and hepatic venous plasma glucose concentration were recorded. Stereotaxic microinjection of PGD2, E1, E2, and F2 alpha produced hyperglycemia and hyperthermia. The relative order of potency in hyperglycemia, PGF2 alpha greater than D2 greater than E1 greater than E2, was not consistent with that of hyperthermia, PGE2 greater than F2 alpha greater than E1 greater than D2, which suggests that hyperglycemia was a primary, not secondary, response to hyperthermia. Injection of PGF2 alpha caused a dose dependent (5-200 micrograms) increase in the hepatic venous plasma glucose level. Neither the injection of PGF2 alpha (50 micrograms) into the cortex nor into the systemic vein caused hyperglycemia. The injection of PGF2 alpha into the ventricle resulted in the increase of not only glucose, but also glucagon, epinephrine, and norephinephrine in the hepatic venous plasma. However, constant infusion of somatostatin through the femoral vein completely prevented the increase of glucagon after administration of PGF2 alpha, although the increase of plasma glucose level was still observed. PGF2 alpha-induced hyperglycemia did not occur in adrenodemedullated rats. Intravenous injection of naloxone or propranolol did not affect the hyperglycemia, but phentolamine significantly prevented the hyperglycemic effect of PGF2 alpha. These results suggest that intraventricular PGF2 alpha affects the central nervous system to produce hyperglycemia by increasing epinephrine secretion from the adrenal medulla.     

~（18）F-FDG PET/CT扫描对孤立性肺结节病诊断价值的探讨

目的本文运用18F-FDG PET/CT对孤立性肺结节病进行扫描来探讨其诊断价值。方法患者禁食6小时以上,按0.12 mci/kg经静脉注入18F-FDG示踪剂于体内。注射前监测血糖,需要注射胰岛素控制血糖在≤7.8 mmol以下,再行静脉注入18F-FDG示踪剂。注射后平静休息60 min,然后,在自然平静呼吸下行全身GE Discovery LS PET/CT扫描仪检查。结果病理检查显示21例诊断肺癌,8例为良性肿瘤;PET/CT扫描检查显示23例诊断肺恶性肿瘤,6例患者为良性肿瘤。结论 18F-FDG-PET/CT显像对SPN有很好的诊断价值,能进一步提高诊断的准确率,值得临床广泛开展。     

The effect of chronic prolactin administration upon the blood sugar,insulin and free fatty acid response to a glucose load in the dog

Summary The effect of chronic prolactin treatment on blood sugar, serum immunoreactive insulin and free fatty acid levels has been studied in normal dogs in the post-absorptive condition and during an i.v. glucose tolerance test. It was observed that: 1) the chronic administration of prolactin failed to affect either blood sugar or serum immunoreactive insulin levels in these animals in the post-absorptive condition and induced a very minor non-significant increase in serum free fatty acid concentration; 2) although prolactin chronic administration induced a moderate reduction in the blood sugar response in the first fifteen min after the glucose load, the average glucose level, k_glucose, and serum IRI profile were unaffected; 3) prolactin administration slightly accelerated the fall of FFA levels during glucose administration as well as the return to baseline values in spite of the high blood glucose and insulin levels. In dogs having undergone chronic prolactin treatment the serum FFA concentration was higher than in non injected animals in the final stages of the test, i.e. at the moment when blood glucose and insulin had returned to basal levels. The physiological significance of these changes is discussed. Traduzione a cura degli AA.     

Effect of cortisol on utilization and hepatic release of glucose in the marsupial brush-tailed opossum, Trichosurus vulpecula.

Brush-tailed opossums were prepared surgically with indwelling heatic and jugular venous catheters for blood sampling without disturbance in the conscious state. Hepatic extraction of Rose Bengal was 21 +3 (s.d.) % and hepatic clearance, used as a measure of hepatic blood flow, was 42.5 +7 ml/kg/min. Hepatic relaease of new glucose, calculated from the thorias vena caval-hepatic venous difference in glucose specific activity at equilibrium during i.v. infusion of [14C]glucose and hepatic blood flow, was 3.5 + o.0 mg/kg/mim. This was not changed by i.v. infusions of 10% ethanolic aline or cortisol in ethanolic saline, at 1mg/kg/h for 90 min, although the cortisol infusion caused the peripheral blood glucose concentration to rise form 56.5 + 7.3 to 83.2 + 10.3 mg/100ml. The rate of metabolic clearance of glucose fell from 6.1 +1.1 to 4.2 +0.9 ml/kg/min during i.v. cortisol infusion. Daily i.m. injection of 1 mg cortisol accetate/kg for 5 days caused an increase in hepatic new glucose release to 8.0 + 1.6 mg/kg/min. The findings support the propostion that, in the marsupial, the short-term effect of cortisol on plasma glucose concentration is due to inhibition of peripheral glucose utilization, whereas the long-term effect is due to increased hepatic glucose production.     

Evaluation of the antibiotic effect of treatment of maxillary sinusitis.

As the effect of antibiotic treatment of maxillary sinusitis has been questioned, the elimination of bacteria from sinus secretions was studied during antibiotic treatment. Penicillin V, azidocillin, tetracycline or doxycycline was administered to 54 patients with maxillary sinusitis. Samples of sinus secretion were aspirated both before treatment and 2-3 days after the onset of treatment. When the antibiotic concentration was below the upper limit of MIC for sensitivity group 1, bacterial growth was present in practically all samples. When the antibiotic concentration equalled or was above this limit, there was no bacterial growth in about half of the samples. A prerequisite for antibiotic effect--elimination of bacteria--is that the antibiotic concentration is well above the MIC of the bacteria at the site of infection. The choice between bactericidal or bacteriostatic antibiotics appeared unimportant. Bacterial survival in the maxillary sinus despite a high antibiotic concentration in the sinus illustrates that MIC values determined in the laboratory do not always mirror the sensitivity of bacteria to antibiotics in vivo.     

Effect of a large dose of insulin and of blood sugar level on glucose uptake in tissues of eviscerated nephrectomized rats

Summary Eviscerated nephrectomized rats were used as peripheral tissue preparations for the study of insulin tolerance. In these experiments, the amount of glucose necessary to maintain a hypoglycaemic, normoglycaemic or hyperglycaemic level with and without a large dose of insulin was determined by constant intravenous infusion of glucose. Without insulin, the hypoglycaemic and the hyperglyeaemic levels were maintained with the same amount of glucose as that required in normoglycaemia. With a large dose of insulin, the glucose requirement was strikingly increased. In comparison with the values obtained at corresponding blood sugar levels without insulin, the increase of glucose requirement was about 3-fold at the hypoglycaemic, 10-fold at the normoglycaemic and 20-fold at the hyperglycaemic levels respectively. A confirmation of the results obtained by the infusion technique was provided by the observation of the fall in blood sugar concentration following hyperglycaemia due to a single injection of glucose. Without insulin, the fall in blood sugar was a linear function of time, whereas following the injection of a large dose of insulin it was an exponential function of time. The role of peripheral tissues in insulin tolerance is discussed in the light of these results. Taken in part from the thesis submitted by N.Bilić for the Ph.D. degree at University of Zagreb, Yugoslavia. This work was supported in part by grants from the SR Croatian Research Fund 30/0 and the Federal Research Fund 493/1.     

Lack of effect of parathyroid hormone on hepatic glucose metabolism in the dog

It has been suggested that raised levels of parathyroid hormone (PTH) may induce glucose intolerance and impair insulin action in primary as well as secondary hyperparathyroidism. Furthermore, PTH is known to stimulate glycogenolysis in isolated hepatocytes and renal cortical cells. We administered a bolus of bovine 1:84 PTH to 8 awake dogs, and measured hepatic glucose production by the primed-constant ³H-3-Glucose infusion technique for 2 hr. PTH injection had no effect on fasting plasma glucose concentration or hepatic glucose production. Plasma insulin and glucagon, serum ionized and total calcium, and serum phosphate did not show any significant change following PTH administration. Synthetic bovine 1:34 PTH, administered to another 3 dogs using the same experimental protocol, also failed to affect any of the measured parameters. To investigate the possible synergism between PTH and other glycoactive hormones, we infused glucagon (3 ng/min · kg, 5 dogs) or epinephrine (0.1 ng/min · kg, 6 dogs) with or without 1:84 PTH in matched experiments. Glucagon alone caused a 22% rise (p < 0.01) in plasma glucose concentration and a 27% rise (p < 0.05) in hepatic glucose production; epinephrine alone induced a 54% rise (p < 0.01) in plasma glucose and a 39% increase (p < 0.01) in glucose production. When PTH injection was combined with glucagon or epinephrine infusion, no further stimulation of hepatic glucose production was observed. In another 6 awake dogs with portal and hepatic venous and arterial catheters, the hepatic response to PTH was determined both by measuring net hepatic glucose balance (hepatic plasma flow times transhepatic glucose concentration difference) and by tracer methodology. While the two techniques showed excellent agreement, both failed to show any effect of PTH. Four dogs in this group received 1:84 PTH obtained from commercial source. In all the other studies here reported, 1:84 PTH prepared in our laboratory was used. Both preparations caused a marked rise in phosphate excretion in dogs, and had the same potency as standard synthetic bovine 1:34 PTH in stimulating c-AMP generation by isolated renal tubular membranes. We conclude that the acute administration of PTH does not stimulate hepatic glucose production in the dog.     

Minocycline-induced loss of potassium from erythrocytes: identification of a family with an augmented response.

The effect of several tetracycline antibiotics of human erythrocytes was examined because of previous findings that these drugs bind to erythrocyte membranes. Minocycline and cetocycline, two highly lipid-soluble analogues, but not tetracycline, induced loss of K+ from red blood cells. Loss of K+ increased linearly with time of incubation, concentration of minocycline, and temperature. The effect of minocycline was inhibited by plasma and calcium. The cells from one volunteer consistently showed an augmented response to minocycline; similar findings for family members of the volunteer suggested a dominant autosomal mode of inheritance. The only abnormality noted in the subject was mild reticulocytosis and a slightly reduced K+ content in his red blood cells. Preliminary studies did not demonstrate alterations in protein composition of his red blood cell membranes, enhanced osmotic fragility, or defects in Ca++-dependent or ouabain-sensitive (Na+-K+)-dependent adenosine triphosphatase activity. The exact site of the minocycline effect remains to be determined.     

Glucagon, its discovery and description and the work of Max Bürger

After intravenous injection of technical insulin (lower degree of purity) already in 1923 Murlin observed transient initial increases of blood sugar. He suggested that this would be caused by another hormone and he gave him the name of glucagon. Nearly from 1928 Bürger dealt with the synergistic effect of muscle work and intravenous application of insulin on the blood sugar. Here he also established the blood sugar increasing principle glucagon. Subsequently by animal experimental and clinical examinations he essentially contributed to the characterization of the substance itself and its mode of action. He always acknowledged the priority of Murlin. The statement of the A-cells of the pancreas as the place of the synthesis of glucagon, the clarification of its structure and its pure preparation caused the fact that nowadays comprehensive knowledge about the second pancreatic hormone is available.     

An Evaluation of Secondary Failure to Tolbutamide Therapy

Summary: An evaluation of the hypoglycaemic effect of tolbutamide was performed over 69 months in 50 newly diagnosed ketosis resistant diabetics who were predominantly obese, female, and Negro in origin. All were participants in the University Group Diabetes Programme, and were randomly assigned to four treatment groups (placebo, tolbutamide, constant insulin, and variable insulin), which were indistinguishable by baseline characteristics.
The hypoglycaemic effect of intravenously administered tolbutamide showed no evidence of change with time and was not significantly different in tolbutamide treated patients. The hypoglycaemic effect of orally administered tolbutamide in the fasting state was also maintained throughout. After a glucose load a specific impairment of the hypoglycaemic effect of tolbutamide was noted during the course of the study. However, a progressive rise in blood sugar levels occurred in all treatment groups after the first twelve months of therapy both in the fasting state and after a glucose load, and this was greater than any changes in treatment response. The changes in blood sugar levels were not related to changes in body weight.
The results show that the delayed reappearance of hyperglycaemia associated with tolbutamide therapy is not primarily and drug related phenomenon.     

绞股兰对实验动物血糖水平的影响

绞股兰(Gynostemma PentaphyllumMaki)又名七叶胆,为葫芦科绞股兰属植物。1970年代以来日本学者对其进行了大量的化学及药理研究,研究表明:绞股兰具有抑制肿瘤细胞繁殖,抗细胞衰老,增加细胞衰老,增加细胞传代次数,降低其氧化脂质,     

Effects of propranolol on blood sugar,insulin and free fatty acids

Summary Three types of experiment were carried out in normal subjects to determine the effect of therapeutic doses of oral Propranolol on 1. the blood sugar, plasma insulin and free fatty acids (FFA) during prolonged fasting and exercise, 2. intravenous glucose tolerance and the rise in insulin level after intravenous glucose, and 3. the intravenous glucose tolerance on exercise. Propranolol caused only slight lowering of the blood sugar in normals, even after 24 h fasting. This was most noticeable during exercise. There was no significant effect of Propranolol on fasting insulin levels, on glucose tolerance at rest or exercise, or on the response of plasma insulin levels to intravenous glucose. Lowering of plasma FFA levels was found in all subjects when taking Propranolol particularly during and after exercise. Possible mechanisms of hypoglycaemia in those cases reported in the literature are discussed. It is concluded that hypoglycaemia is not a major problem in Propranolol therapy.These studies were carried out as part of an elective period in the Departments of Medicine and Experimental Pathology in the University of Birmingham.     

In-feed antibiotic effects on the swine intestinal microbiome

Antibiotics have been administered to agricultural animals for disease treatment, disease prevention, and growth promotion for over 50 y. The impact of such antibiotic use on the treatment of human diseases is hotly debated. We raised pigs in a highly controlled environment, with one portion of the littermates receiving a diet containing performance-enhancing antibiotics [chlortetracycline, sulfamethazine, and penicillin (known as ASP250)] and the other portion receiving the same diet but without the antibiotics. We used phylogenetic, metagenomic, and quantitative PCR-based approaches to address the impact of antibiotics on the swine gut microbiota. Bacterial phylotypes shifted after 14 d of antibiotic treatment, with the medicated pigs showing an increase in Proteobacteria (1-11%) compared with nonmedicated pigs at the same time point. This shift was driven by an increase in Escherichia coli populations. Analysis of the metagenomes showed that microbial functional genes relating to energy production and conversion were increased in the antibiotic-fed pigs. The results also indicate that antibiotic resistance genes increased in abundance and diversity in the medicated swine microbiome despite a high background of resistance genes in nonmedicated swine. Some enriched genes, such as aminoglycoside O-phosphotransferases, confer resistance to antibiotics that were not administered in this study, demonstrating the potential for indirect selection of resistance to classes of antibiotics not fed. The collateral effects of feeding subtherapeutic doses of antibiotics to agricultural animals are apparent and must be considered in cost-benefit analyses.     

The mechanism of the effect of oxytocin on plasma concentrations of glucose, insulin and glucagon in conscious dogs

Injections and infusions of oxytocin into conscious dogs caused an increase in plasma concentrations of glucose, insulin and glucagon. When blood glucose was clamped at a raised level the injection of oxytocin still increased insulin and glucagon concentrations in plasma. Infusion of somatostatin suppressed plasma concentrations of glucagon and insulin but did not prevent oxytocin-induced increments in blood glucose. Injection of oxytocin still caused a marked release of glucagon, whereas the insulin response was greatly diminished. When endogenous insulin and glucagon secretion was suppressed by infusion of somatostatin and glucose levels were stabilized by concomitant infusions of glucagon and insulin, injections of oxytocin did not alter blood glucose concentrations. It is concluded that the increase in blood glucose following the administration of oxytocin is secondary to the release of glucagon and that oxytocin exerts a direct stimulatory effect on glucagon and possibly insulin secretion.     

Comparison of blood glucose and insulin concentrations in man after intravenous injection of 1.0, 0.1 and 0.01 mg of glucagon (author's transl)]

The effect of various doses of glucagon on hyperglycemic action and insulin secretion was studied in 12 healthy volunteers to determine whether 1.0 mg of glucagon, the usual dose, is indeed necessary to obtain an adequate hyperglycemic response. For this purpose 2.0, 1.0, 0.5, 0.1 and 0.01 mg of glucagon (Novo) were used respectively to confirm the existence of a dose response relationship. Of these doses, three different doses were administered to one subject within a week after overnight fasting. Maximum increment of blood glucose was not statistically significant between 1.0 (32.5+/-4.4mg/dl) and 0.01 mg (29.5+/-2.7 mg/dl), averaging about 30 mg/dl. The peak time of blood glucose concentration was 30 min. with 1.0 mg, and 10 min. with 0.01 mg. On the contrary, insulin secretion after glucagon injection decerased as the dose decreased. Maximum blood insulin (IRI) concentration was 69.7+/-17.2muu/ml with 1.0 mg, and 25.3+/-11.3 muu/ml with 0.0l mg (p less than 0.05). The peak time of insulin concentration was 2 min. with 1.0 mg, and 10 min. with 0.01 mg. From these data it is concluded that the dose response relationship after intravenous glucagon injection of between 1.0 mg and 0.01 mg doses exist concerning insulin sercretion, but not concerning hyperglycemic response.     

Modeling the Effect of Subcutaneous Lixisenatide on Glucoregulatory Endocrine Secretions and Gastric Emptying in Type 2 Diabetes to Simulate the Effect of iGlarLixi Administration Timing on Blood Sugar Profiles

Background:As type 2 diabetes (T2D) progresses, intensification to combination therapies, such as iGlarLixi (a fixed-ratio GLP-1 RA and basal insulin combination), may be required. Here a simulation study was used to assess the effect of iGlarLixi administration timing (am vs pm) on blood sugar profiles.Methods:Models of lixisenatide were built with a selection procedure, optimizing measurement fits and model complexity, and were included in a pre-existing T2D simulation platform containing glargine models. With the resulting tool, a simulated trial was conducted with 100 in-silico participants with T2D. Individuals were given iGLarLixi either before breakfast or before an evening meal for 2 weeks and daily glycemic profiles were analyzed. In the model, breakfast was considered the largest meal of the day.Results:A similar percentage of time within 24 hours was spent with blood sugar levels between 70 to 180 mg/dL when iGlarLixi was administered pre-breakfast or pre-evening meal (73% vs 71%, respectively). Overall percent of time with blood glucose levels above 180 mg/dL within a 24-hour period was similar when iGlarLixi was administered pre-breakfast or pre-evening meal (26% vs 28%, respectively). Rates of hypoglycemia were low in both regimens, with a blood glucose concentration of below 70 mg/dL only observed for 1% of the 24-hour time period for either timing of administration.Conclusions:Good efficacy was observed when iGlarlixi was administered pre-breakfast; however, administration of iGlarlixi pre-evening meal was also deemed to be effective, even though in the model the size of the evening meal was smaller than that of the breakfast.     

Diarrhoea associated with medullary carcinoma of the thyroid

Diarrhoea, which is present in roughly one third of cases of medullary carcinoma of the thyroid, was investigated in five cases.Excessive loss of water and electrolytes in the stools was the major factor. Steatorrhoea was mild or absent, and intestinal absorption of glucose and vitamin B(12) was normal; the histological appearance of the small intestinal mucosa was normal or subnormal. Water and sodium diarrhoea seems to be linked to a sometimes considerable increase in the rate of transit through the small intestine and colon, and may be relieved by codeine or codethyline. The frequent increase in the maximum blood sugar level during an oral tolerance test should not be interpreted as evidence of a paradiabetic condition. In fact, the intravenous glucose tolerance test is usually normal and the excessive rise in blood sugar after oral administration seems to be the consequence of the increased rate of transit through the small intestine.The link between the tumour and the disordered motility seems definite in view of certain cases in which removal of the tumour caused the diarrhoea to disappear immediately. Production by the tumour of serotonin or other derivatives of tryptophan or of kallikrein, which activates bradykinin, is rare. With regard to prostaglandins, high concentrations have been observed in the tumours and in the venous blood draining the tumours, but their presence in systemic blood is inconstant. The only hormonal substance, concentration of which seems to be definitely increased in the systemic blood of patients with a medullary carcinoma of the thyroid, is thyrocalcitonin but this hormone does not seem to have any effect on the motor activity of the digestive tract.