bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Sodium Tolbutamide on Pregnant Albino Rats and Their Young
Authors: Dawson John E 
Published: December 2014

The sodium salt of tolbutamide, in dosages ranging from 12.5 mg./kg. to 125 mg./kg. body weight, was administered to pregnant albino rats to determine its effect upon litter size, individual fetal weight, normal development of the young, and the fetal skeleton.
As the dosage level increased, a statistically significant decrease in fetal weight was observed. Tolbutamide administration had no detrimental effect upon the total number of implantations; however, a large number of resorptions occurred at the 125 mg./kg. level resulting in a decreased litter number.
The number of rats having litters with fetuses weighing less than three grams increased as the dosage increased from 12.5 mg./kg. to 100 mg./kg. levels.
No adverse effect on the maternal animal was noted except at the 100 mg./kg. and 125 mg./kg. levels. At these levels all animals experienced a localized tetanic response which varied in duration according to the level of injection.
The number of sternebrae, metacarpals, and metatarsals, as well as long bones, indicated that the number and size of bones varied inversely with increased dosage levels.
Normal skeletal development occurred despite dosages up to and including the 37.5 mg./kg. level. Abnormalities were observed from the 50 mg./kg. to the 125 mg./kg. level of administration.
Studies of Incorporation of Radioactivity into Lipids by Human Blood: II. Pattern of Incorporation of Radioactivity into Fatty Acids by Platelets from Normal Subjects and Patients in Diabetic Acidosis
Authors: Awai Kozi , Hennes Allen R 
Published: December 2014

Platelets from diabetics in acidosis incorporate significantly less C-14 into fatty acids than do platelets from control subjects. This decrease in incorporation of C-14 into fatty acids is not uniform. Incorporation of C-14 into myristic and palmitic acids, fatty acids presumably made by de novo synthesis, is suppressed to a much greater extent than is incorporation into other fatty acids.
Since some of these abnormalities of incorporation of C-14 by platelets from comatose diabetics could represent isotope dilution effects, we have been particularly interested in the analysis of these data in terms of percentage of total fatty acid C-14 incorporated into the various groups of fatty acids. Platelets from diabetics in acidosis have a pattern of incorporation of C-14 into platelet fatty acids which is much different from that of normal platelets. There is a great decrease in percentage of C-14 in myristic and palmitic acid with a relative increase in percentage of C-14 in fatty acids with retention time corresponding to arachidic acid (20:0) or greater. A significant increase in relative percentage of C-14 in fatty acids containing ten carbons or less is also seen. These findings presumably mean that the cytoplasmic or malonyl CoA pathway, which is involved primarily in synthesis of palmitic and myristic acids, is suppressed greatly in diabetic acidosis, while the mitochondrial or chainlengthening pathway is suppressed to a much smaller degree, or is actually stimulated. It is, therefore, important to consider qualitative as well as quantitative alterations in fatty acid synthesis in diabetes.
Galvanic Skin Reflex and Plasma Free Fatty Acids During Insulin Reactions
Authors: Bolinger Robert E , Stephens Ronald , Lukert Barbara , Diederich Dennis 
Published: December 2014

Hypoglycemic reactions, induced by insulin (0.2 U./kg. intravenously), were studied in sixteen diabetic and twelve nondiabetic control subjects. The course of the reaction was monitored by continuous recording of the galvanic skin reflex (GSR) and by determination of the levels of blood glucose and free fatty acids (FFA) at 10, 20, 30, 60 and 120 minutes. Symptoms of reaction appeared in all of the controls at 32 ± 12 minutes after the insulin at a mean blood glucose level of 22 ± 7 mg. per 100 ml., and in the eleven of the diabetics at 70 ± 30 minutes and at a mean glucose level of 280 ± 192 mg. per 100 ml.
Onset of the insulin reaction was documented by a sudden drop in GSR which corresponded with the onset of symptoms. The GSR fell to a mean of 75 per cent of the baseline value and returned to the baseline thirty minutes later. All of the controls and nine of the diabetics showed the GSR response.
The GSR correlates well with symptoms of insulin reactions. Evidence of insulin reaction occurring in nine diabetic patients at high blood glucose levels is documented by GSR response.
Free fatty acids (FFA) in the plasma showed a more rapid return to baseline values in those subjects manifesting the quicker GSR response. The change in the GSR is a more sensitive though less specific measure of the homeostatic response to insulin than the change in the FFA.
Statistical Aspects of the Mouse Diaphragm Test for Insulin
Authors: Wardlaw A C , Van Belle G 
Published: December 2014

This paper describes a variety of test designs and statistical technics for use with the mouse hemidiaphragm method for assaying insulin.
Designs for both qualitative tests and quantitative assays are presented together with examples. The only object of the qualitative test is to detect the presence of insulin in a sample, and this is done by demonstrating a significantly higher level of glycogen in hemidiaphragms incubated with the sample than in those incubated with insulin-free medium. Procedures for analysis of variance and for making tests of significance are given.
The aim of the quantitative assay is to estimate the potency in milliunits per milliliter and to assign confidence limits. For this purpose a test with standard insulin and the unknowns, each at two dose-levels, is utilized. The two-dose design is applicable to the assay of insulin either with or without anti-insulin serum. As previously reported, the use of this serum greatly increases the precision (λ-value) of the assay by increasing the slope of the doseresponse curve without simultaneously increasing the standard deviation. The antiserum may also be used to “bracket” the potency of samples within known limits, prior to carrying out a two-level quantitative assay.
Methods are described for ihe analysis of variance of the two-dose design and for the calculation of relative potency and confidence limits. Procedures are given for assessing the validity of the assays and also for combining the results of several independent tests.
Ethanol Metabolism and Experimental Diabetes
Authors: Clark William C , Hulpieu Harold R , Haines Robert J 
Published: December 2014

The influence of diabetes in dogs, varying in intensity from a mild, acute insulin deficiency produced by antiinsulin guinea pig serum to a severe diabetes in chronic pancreatectomized dogs deprived of insulin for seven days, was investigated.
The experimental diabetes, regardless of its severity, did not depress the rate of ethanol metabolism in these experiments. In not one of the experiments did the diabetic dog have an ethanol disappearance rate lower than the range observed in the control experiments. In fact the rate tended to be higher than that of the control experiments but the difference was not statistically significant. These findings confirm and extend those of Kinard and Cox but do not agree with those of B. B. Clark et al.
Insulin I-131 Binding in Serum from Normal and Diabetic Subjects by Ultracentrifugation and Gel Filtration
Authors: Chao P Y , Karam J H , Grodsky G M 
Published: December 2014

Ultracentrifugation and gel filtration were used to test for specific insulin-I-131 binding protein in the serum of normal subjects and in patients with overt or potential diabetes.
Such technics permit study of sera at physiologic pH, with physiologic concentrations of exogenous insulin added. They also eliminate the interference of electrical fields and, in ultracentrifugation, the need for artificial supporting media.
Whereas a specific binding protein was readily demonstrable in the serum of insulin-treated patients with high antibody titers, there was no evidence of a protein capable of binding exogenous labeled insulin in normal subjects nor in the serum of subjects with various types of diabetes and potential diabetes.
Serum from subjects who have a hyper-response of insulin to glucose loads, possibly caused by peripheral antagonism to insulin action, did not bind significant amounts of insulin-I-131.
Effects of Sudden Deprivation and Restoration of Insulin Secretion on Glucose Metabolism in Dogs
Authors: Wrenshall G A , Vranic M , Cowan J S , Rappaport A M 
Published: December 2014

Fourteen subtotally depancreatized aglycosuric dogs had the remaining pedunculated uncinate process enclosed in plastic casing and grafted subcutaneously. After one week the pedicle of the auto graft was clamped for thirty to sixty minutes. In seven dogs given intravenous glucose at the time of clamping, diabetes-like changes in glucose tolerance occurred which increased in magnitude with increasing duration of deprivation of exogenous insulin. In seven fasting dogs the blood glucose level was rising in the four- to tenminute interval after clamping. In three such dogs (one under local and two under Nembutal anesthesia) the method of successive measured injections of tracer (C-14-glucose U.L.) showed that the rate of glucose appearance had doubled and the rate of its disappearance was decreased to one third at one to thirteen minutes after clamping, resulting in high rates of accumulation of body glucose. The initial increase in the rate of glucose production appears to result from glycogenolysis.
Restoration of blood flow through the autograft (unclamping) caused a prompt decrease in rate of appearance of unlabeled glucose and increase in its rate of disappearance, resulting in restoration of these rates to their preclamping values within fifteen hours, and to a restored tolerance for intravenous glucose. The rapidity of these rate changes at clamping and unclamping demonstrates the importance of the continuous secretion of native insulin to prevent glucose accumulation in the partially depancreatized dog.
Studies of Incorporation of Radioactivity into Lipids by Human Blood: IV. Abnormal Incorporation of Acetate 1-C-14 into Fatty Acids by Whole Blood and Platelets from Insulin Independent Diabetics
Authors: Hennes Allen R , Awai Kozi 
Published: December 2014

The incorporation of acetate 1-C-14 into fatty acids by whole blood and platelets from insulin independent diabetics has been determined.
Whole blood from insulin independent diabetics incorporates significantly less C-14 into fatty acids than does whole blood from controls. As in previously reported studies done with blood cells from ketotic and nonketotic insulin dependent diabetics, a decreased percentage of fatty acid C-14 in palmitic acid (16:0) is found. This, however, exists as an isolated abnormality in whole bLiod from insulin independent diabetics. This abnormality may persist in some patients even when the fasting blood sugar is normal.
The incorporation of acetate C-14 into fatty acids by platelets from insulin independent diabetics is quite similar to that of the control group. However, the pattern of incorporation of C-14 into fatty acids is abnormal. Percentage of C-14 in both myristic and palmitic acids is decreased, while percentage of C-14 in saturated and unsaturated fatty acids with retention time corresponding to 20:0 or greater is increased. These abnormalities bear no relationship to the fasting blood sugar at the time of study.
These findings apparently mean that de novo synthesis of fatty acids is impaired in blood cells from both insulin dependent and insulin independent diabetics, while chain lengthening is relatively little affected.
Patterns of Decrease of Free Fatty Acids During Glucose Tolerance Tests
Authors: Shafrir Eleazar , Gutman Alisa 
Published: December 2014

In normal subjects the decrease of serum FFA levels after an oral glucose load was prompt and persistent with a drop to below 200 μEq./L. at one hour. Among patients with mild diabetes about 40 per cent showed FFA response similar to normal despite abnormal GT. Another 40 per cent diabetic patients had a delayed FFA decrease with a drop to minimum levels only after two hours and about 15 per cent of the patients had a deficient response with only a small decrease in FFA after glucose ingestion. In the two latter groups the slopes of FFA decrease (—log [FFA]/t) were less steep, indicating that the failure to reach the minimum level of normal subjects was not related to the higher initial serum FFA concentration.
The occurrence of normal pattern of FFA decrease among a large proportion of diabetics was taken as an indication of normal function of adipose tissue. The tissue remained sensitive to ILA even when available in diminished amounts as assessed by comparisons of rises in the glucose uptake of rat diaphragm. A delayed FFA decrease appeared associated with late appearance of ILA, whereas the inability of adipose tissue to arrest the outflow of FFA was consistent with scarcity of ILA. The differential effectiveness of insulin as a result of selective antagonism toward its action on tissues is discussed.
Childbearing Prior to Recognition of Diabetes: Recollected Birth Weights and Stillbirth Rate in Babies Born to Parents Who Developed Diabetes
Authors: Malins J M , FitzGerald M G 
Published: December 2014

Of 2,348 children born to women who later developed diabetes, 12.6 per cent had a recollected birth weight exceeding 10 lb. (4.5 kg.), compared with 5 per cent of a control group. The proportion of these heavy babies did not increase, as the diagnosis approached and was as great forty to sixty as zero to twenty years betore the diabetes was recognized. It was the same in each birth rank.
Men show no increased tendency to beget very large babies before the onset of diabetes.
The stillbirth rate in the five years preceding the diagnosis of diabetes was 13.8 per cent but before that period was not in excess of that in the general population.
Mass Screening for Diabetes in a Metropolitan Area Using Finger Blood Glucose after a Carbohydrate Load
Authors: Kent Gerald T , Leonards Jack R 
Published: December 2014

New technical methods and instruments have made possible large scale screening for diabetes. A palatable, refreshing, carbonated drink, containing the equivalent of 75 gm. of glucose, was developed which makes possible uniform carbohydrate administration without nausea. Portable, automatic, analytical instruments, capable of rapid and accurate determination of glucose by a ferricyanide reduction method, were designed and built. Only .075 ml. of blood, readily obtainable from a finger prick, was required. The result was available in seven minutes, each machine being capable of forty analyses per hour. The equipment was incorporated into mobile units for testing in a community, or setting up in industrial plants.
Confirmatory carbohydrate tolerance tests were done whenever possible on all individuals having capillary blood glucose levels above 140 mg. per 100 ml., two hours after the carbohydrate drink.
In a completed Pilot Study, 8,790 individuals were screened, with 709 initially positive; 560 individuals returned for carbohydrate tolerance tests, and of these 407 had abnormal curves, for atotal over-all incidence of 4.5 per cent.
An advantage of this method is that every individual screened has had, in effect, two carbohydrate tolerance tests before being referred to his physician.
Enzymatic Defects as Causes of Hypoglycemia
Authors: Illingworth Barbara 
Published: December 2014

A review of some of the enzymatic causes of hypoglycemia is presented. Evidence that there may be a diminished production of epinephrine or glucagonin certain cases of hypoglycemia is reviewed and the relationship of these hormones to the activation of glycogen phosphorylase is discussed.
Galactosemia, fructose intolerance and glycogen storage diseases are cited as examples of hereditary disorders attributable to specific enzyme defects and often accompanied by hypoglycemia. The deficiencies of galactose-1-phosphate uridyl transferase in galactosemia and aldolase in fructose intolerance result in the accumulation in the tissues of toxic quantities of intermediary metabolites (galactose-1-phosphate and fructose-1-phosphate, respectively) which secondarily affect the activities of other enzymes. In Type I glycogenosis, the hypoglycemia is explained by the deficiency of glucose-6-phosphatase. Other types of glycogenoses often provide examples of intermittent hypoglycemia. The role of gluconeogenesis in the maintenance of blood sugar levels has not been reviewed.
Carbohydrate Tolerance and Diabetes in a Total Community, Tecumseh, Michigan: 1. Effects of Age, Sex, and Test Conditions on One-hour Glucose Tolerance in Adults
Authors: Hayner Norman S , Kjelsberg Marcus O , Epstein Frederick H , Francis Thomas 
Published: December 2014

During initial examinations of the residents of Tecumseh, Michigan, one-hour 100-gm. glucose tolerance tests were applied to 2,983 persons sixteen years of age and older.
Distributions of one-hour blood glucose values divided by age, sex and interval since last food were unimodal with slight skewing toward higher levels. In general, means and variances of distributions for men and women of the same age tested under like circumstances were almost identical. In contrast, age and recent food independently exerted striking effects on one-hour levels. With increasing age through the seventh decade the whole one-hour glucosemia distribution shifted steadily toward higher levels, the slope of its regression on age approximating 13 mg. per 100 ml. per decade. Persons challenged within four hours of eating exhibited one-hour values averaging 25 mg. per 100 ml. below those of similar ages challenged at longer intervals after eating. The degree of depression of the one-hour value by recent food increased detectably with the total carbohydrate intake during the last four hours. No diurnal variation was noted; seasonal variation was observed only in males, whose values were slightly higher in autumn months than in other seasons.
The consistent observation of a linear age gradient challenges current diagnostic criteria for diabetes which take no account age. Instead, the present data suggest that much of what has been designated as maturity-onset diabetes results from a diminution of carbohydrate tolerance with age which is characteristic of the entire population. Accordingly, hypotheses regarding the etiology of diabetes must be rexamined.
Effect of a New Hypoglycemic Agent, 3,5-Dimethylpyrazole, on Carbohydrate and Free Fatty Acid Metabolism
Authors: Gerritsen George C , Dulin William E 
Published: December 2014

As a hypoglycemic agent, 3,5-dimethylpyrazole (U-6245) was found to be fifty-four times more potent orally than tolbutamide in glucose-injected, fasted intact rats. U-6245 increased glucose oxidation by intact rats. It lowered plasma free fatty acids but not blood sugar of eviscerate rats and was effective in decreasing the fasting bloodsugar levels of alloxan-diabetic rats which were unresponsive to tolbutamide. U-6245 markedly depressed plasma FFA fifteen minutes to three hours after its administration.
The mechanism of hypoglycemic activity of 3,5-dimethylpyrazole is not the same as insulin, sulfonylureas or biguanides in that: (1) It is ineffective in lowering the blood sugar of eviscerates while insulin is. (2) U-6245 is active in alloxan diabetic rats which are unresponsive to tolbutamide. (3) The pyrazole increases glucose oxidation and biguanides do not. Although the mechanism of action of 3,5-dimethylpyrazole is not understood, data are presented which support the hypothesis that its action may depend on its effect on plasma FFA and also on the presence of the liver and/or intestinal tract. Since the pyrazole increases glucose oxidation in intact rats, it appears that at least part of its action may be due to the stimulation of glucose oxidation by the intestinal tract and/or liver.
Severe Prolonged Hypoglycemia Following Tolbutamide and Carbutamide Treatment
Authors: Heikinheimo Rauno 
Published: December 2014

Two elderly, nondiabetic patients with uremia, one of whom had received on the preceding day one gram of carbutamide per os and the other one gram of tolbutamide intravenously, had severe, prolonged hypoglycemic reactions. The reaction lasted for six days in the former patient and was so severe that daily administration of glucose was necessary. The patient died from uremia thirteen days after taking the drug. The other patient was markedly hypoglycemic until his death three and one-half days later. A fairly large benign adrenocortical adenoma was found at autopsy in each patient.
The same agents were also administered once to four severely uremic patients, but no significant depression of the blood sugar level was elicited. The cause of the prolonged hypoglycemia in some subjects remains undetermined.
Carbohydrate Metabolism in Hyperadrenocorticism
Authors: Pupo Armando Aguiar , Wajchenberg Bernardo L , Schnaider José 
Published: December 2014

Investigations of tolerance to oral and intravenous glucose, intravenous and intra-arterial insulin, intravenous tolbutamide, and to subcutaneous glucagon were made in twelve patients with hyperadrenocorticism. The findings varied among patients, but certain trends were apparent.
Fasting blood sugar concentrations tended to be low. The results of oral glucose tolerance teats were diabetic in eleven patients. The rate of glucose disappearance during glucose loading was normal or increased in all. Intravenous tolbutamide caused prolonged hypoglycemia in three of five patients. Hypoglycemia after intravenous and intra-arterial insulin was decreased. Depression of serum phosphorus was less than normal. Glucagon caused a rise in blood sugar above that of normals.
The findings suggest that there is a normal or even increased rate of glucose utilization in clinical endogenous hyperadrenocorticism. The data are compatible with the view that the action of insulin on muscle tissue may be decreased with shift to other areas, perhaps adipose tissue.
Pancreatic A-Cell Tumor Associated with Severe Diabetes Mellitus
Authors: Yoshinaga Tetsuo , Okuno Giichi , Shinji Yoshitake , Tsujii Tsutomu , Nishikawa Mitsuo 
Published: December 2014

This paper describes a case of pancreatic A-cell tumor associated with severe diabetes mellitus and high levels of serum extractable glucagon-like activity. The tumor was detected clinically about six months before diabetes mellitus became manifest.
It is suggested that the development of diabetes mellitus in this case may have been influenced by the tumor and by the elevated serum glucagon-like activity.
Preferential Beef/Pork Insulin-binding Capacity: Radioimmunoelectrophoretic and Chromatographic Data in Patients with Dermal Reactions to Insulin
Authors: Devlin James G , O'Donovan D K 
Published: December 2014

In 50 per cent of a beef insulin-treated diabetic population immediate whealing to beef insulin was found. Only 6.2 per cent showed a similar response to pork insulin.
The plasma of patients with immediate whealing to beef insulin binds beef insulin in preference to pork insulin.
No difference in in vitro binding titer was found between groups exhibiting immediate whealing responses to insulin and those showing no such reaction. It has been confirmed by radioimmunoelectrophoretic and chromatographic procedures that the insulin IgG antibody complex can be fractionated into gamma1 and gamma2 components. The gammaj component was found to be relatively more clearly differentiated by radioimmunoelectrophoresis in the majority of patients with dermal responsiveness. The possible significance of these findings is discussed, and it is proposed that the whealing response described may rest on an antibody of some sort, although we were unable to incriminate either the insulin binding or the P.K. reaginic types in the serum.
An IgM insulin binding antibody was detected in four patients, three of whom were having acute local reactions at the site of insulin injection and two of whom had been receiving insulin for approximately four weeks.