bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Blood Saccharoid Content in Neuropsychiatric Patients
Authors: Baiter Abraham M , Efron Herman Y
Published: December 2014

Glucose tolerance tests were obtained in 430 psychiatric inpatients with both the Folin-Wu and Somogyi-Nelson methods on the same blood sample. Blood was drawn in the fasting state and at one-half, one, two and three hours after ingestion of glucose. By the Somogyi-Nelson method the curves of 170 subjects were classified as normal and 260 as abnormal. The saccharoid content of the blood was operationally defined as the Folin-Wu value minus the Somogyi-Nelson value with the latter taken as the “true” blood sugar. In marked contrast to previous studies of others with nonpsychiatric subjects the mean saccharoid values were not constant in either the normal or abnormal group but varied significantly from one time period to the next. The variations in saccharoids observed in the abnormal group over the testing interval were different from the variations for the normals. Within each group, there was no association between age and either saccharoid content or blood sugar level. Saccharoid content was not related to deviations from average weight. A “rule of thumb” suggested by the data is that if one wants to estimate “true glucose” from the Folin-Wu with 95 per cent certainty, then the constant to subtract varies with the time interval after glucose ingestion and is in the range of approximately 0 to 47 mg./lOO ml. Estimation of true blood sugar content from a Folin-Wu reading that is close to the borderline range by subtraction of a constant is seen as an extremely dubious procedure.
An Abnormal Insulin in Juvenile Diabetes Mellitus
Authors: Elliott Robert B , O'Brien Donough , Roy Claude C
Published: December 2014

A technic is described for the isolation of insulin from serum using a series of gel nitrations in combination with an interim complexing with guinea pig anti-insulin serum. Insulin thus derived from the serum of juvenile diabetic subjects was shown to be significantly more resistant to insulinase than that from normal persons. It is suggested that there is a genetically determined structural difference in the insulin of diabetic children which contributes importantly to the underlying biochemical disorders of the disease.
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.
Inactivation of Insulin by Adipose Tissue
Authors: Girolamo Mario Di , Rodman Daniel , Malkin Martin F , Garcia Luis A
Published: December 2014

A previous investigation in this laboratory demonstrated that rat adipose tissue contains an insoluble peptidase system which cleaves and inactivates adipokinetic hypophyseal peptides; adipose tissues from the rabbit and guinea pig possess little or no capacity to inactivate these peptides. The present study demonstrates that adipose tissues from the rat or hamster, but not from the rabbit or guinea pig, cleave and inactivate insulin. Incubation of bovine insulin with homogenized adipose tissue from the rat causes cleavage of the peptide into at least seven fragments and disappearance of the peptide's hypoglycemic activity. Unlike native insulin, the insulin fragments which contain tyrosine are soluble in 5 per cent trichloracetic acid. The insulin-inactivating system is located in the insoluble portion of homogenized adipose tissue. Inactivation of insulin does not proceed at a detectable rate at 0° C. The capacity of the insoluble fraction of rat adipose tissue homogenate to cleave and inactivate insulin is abolished by exposure to 100° C. for two minutes. An insulin-inactivating system with the same properties is found in lesser amount in hamster adipose tissue. It is not present in detectable amount in the adipose tissue of the rabbit or guinea pig. The adipose enzyme system which inactivates insulin resembles the system which inactivates hypophyseal peptides in regard to the characteristics described above.
A New Carbohydrate Solution for Testing Glucose Tolerance
Authors: Leonards Jack R , McCullagh E Perry , Christopher Terrence C
Published: December 2014

During the standard 100 gm. glucose tolerance test, nausea or vomiting is a frequent side effect. In preparation for a large-scale survey for detection of diabetes a more palatable solution that causes no side effects was developed. The solution was made of partially hydrolyzed cornstarch, flavored with cola extract, and carbonated, yielding a product that tastes like a popular cola beverage. Glucose tolerance curves in sixty-three subjects after either 75 or 100 gm. of the new carbohydrate solution were, for practical purposes, identical to those after 100 gm. of glucose. Administration of the new solution was exceptionally well tolerated in 85,000 persons thus far tested for diabetes.
Presence of Iron in Osteoid Seams of Bone from Patients with Diabetes Mellitus
Authors: Villanueva A R , Kelin M
Published: December 2014

Iron, demonstrated with the Prussian blue test, has been observed in the osteoid seams that accompany lamellar bone formation in seventeen out of nineteen diabetic cases, while it was absent in this location in all sixty nondiabetic persons used as controls. The iron is homogeneously distributed throughout the osteoid, it is not paniculate, and it is extracellular. This distinguishes it from hemosiderin-bound iron which is both paniculate and usually intracellular.
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.
Effect of Chlorpropamide on Urea Synthesis and Glyconeogenesis in the Liver
Authors: Pogátsa Gábor , Káldor Antal
Published: December 2014

Chlorpropamide present in concentrations of 50 or 100 mg./100 ml. reduces glucose output by isolated rat livers perfused with Tyrode's solution. The release of amino acid nitrogen was increased by chlorpropamide in livers perfused with glucose-free Tyrode's solution but was decreased when both chlorpropamide and glucose were present in the perfusing fluid. Chlorpropamide was without effect on urea production by the isolated perfused liver.
Isoantibodies to Human Pancreas: A Preliminary Report
Authors: Villavicencio E , Thurnau Gary , Goetz Frederick C
Published: December 2014

One hundred and forty-two diabetics, 163 blood bank donors, ten patients with carcinoma of the pancreas, ten patients with chronic pancreatitis, six patients with acute pancreatitis, and a number of patients with miscellaneous diagnoses were tested for evidence of isoantibodies to the pancreas using the tanned cell hemagglutination technic as described by Boyden, the test tube precipitin method, the Ouchterlony gel-diffusion method or a combination of these. None showed isoantibodies to pooled human pancreas. Further investigation of this problem is warranted.
Observations on the Uptake of Insulin Conjugated with Fluorescein Isothiocyanate by Diabetic Kidney Tissue
Authors: Farrant P C , Shedden W I H
Published: December 2014

Kidney tissue from the majority of patients dying with diabetes mellitus was found totake up insulin labeled with fluorescein isothiocyanate. Kidney tissue from patients with renal disease in the absence of diabetes occasionally showed a similar uptake. No insulin uptake was observed in the kidneys of nondiabetic patients dying of causes other than renal disease. These findings were compared with those of a study reported elsewhere.
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.
Potentiation of Insulin Action by Calcium and Magnesium
Authors: Planchart Alfredo
Published: December 2014

Recent experiments have shown that commercial insulin produces an increase in short circuit current across the isolated short-circuited frog skin.1 This in vitro phenomenon was observed only in the presence of Ca++ and Mg++ which suggested that these ions were necessary for the action of insulin in such an experimental system. The present study utilizing intact mice was designed to determine the effect of added Ca++ and Mg++ in an in vivo system.
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.
Stimulatory Effect of Chelating Agents and Mesoxalate on the In Vivo Release of Insulin in the Pancreas of the Dog: The Possible Role of Amino Acids
Authors: Ninomiya Rikuo , Miura Yasusada , Kosaka Kinori , Nakao Kiku , Okinaka Shigeo
Published: December 2014

Plasma ILA has been assayed in the blood of the pancreatic vein in dogs by measuring the fall in blood glucose level in hypophysectomized-adrenodemedullated rats. The infusion of EDTA, L-histidine, glycine and L-leucine into the pancreatic artery increased the ILA in the pancreatic effluent, the increase being most pronounced fifteen to thirty minutes after the cessation of a ten-minute infusion. No increase in the ILA was observed in the pancreatic vein draining the nonperfused pancreatic area. Mesoxalate stimulated the release of insulin, but its effect was not characteristic of the chelating agents with respect to time course of action. Vagotomy abolished the effect of both chelating agents and mesoxalate. These findings indicate the in vivo stimulation of the release of biologically active insulin by chelating agents and mesoxalate.
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.
Magnesium Deficiency and Carbohydrate Metabolism
Authors: Kahil M E , Parrish J E , Simons E L , Brown H
Published: December 2014

Diet-induced magnesium deficiency in puppies resulted in an increased rate of glucose removal from the blood after intravenous glucose infusions. The levels of immunoassayable insulin in the plasma of these animals were comparable to those of the controls. The accelerated removal of glucose from the plasma was reversed with magnesium treatment. Incubation of intact diaphragms from magnesium-deficient rats demonstrated an increased sugar (2-DG) and amino acid (AIB) uptake from magnesiumfree buffer. Although the plasma magnesium concentration rapidly decreased in the deficient rats, a considerably longer period of time elapsed before the changes in sugar transport became apparent. Kinetic studies suggested that the enhanced permeability was due to carrier mediated transport rather than to diffusion. Tissue magnesium levels remained normal despite a significant decrease in the serum magnesium. These studies suggest that some general characteristic of membrane structure and function is affected by the extracellular concentration of magnesium.
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.
Effect of Antagonistic Albumin on Insulin-stimulated Intracellular Metabolic Pathways
Authors: Davidson Mayer B , Goodner Charles J
Published: December 2014

Previous data on incorporation of glucose C-14 into glycogen by the rat diaphragm had suggested that this synthetic pathway was unaffected by the albumin-associated insulin antagonist. To test the hypothesis that only the transport functions of insulin were blocked by this antagonist, studies on two insulin-stimulated intracellular pathways independent of transport were carried out. The increase in tissue levels of the I form of glycogen synthetase seen with insulin was not affected by antagonistic albumin (human fraction V). The D form of glycogen synthetase was also unaffected. However, insulin-stimulated adenine-8-C-14 incorporation into RNA was completely abolished by this albumin. A nonantagonistic albumin (bovine fraction V) by itself increased RNA synthesis indicating that the inhibition of insulin-stimulated RNA synthesis was not a general property of the albumin molecule. The physical-chemical and metabolic characteristics of the albumin-associated antagonist are summarized and are considered to be incompatible with the postulated physiological role for this insulin antagonist.
Rat Serum “Bound” Insulin: In Vivo Biologic Effects in Rats
Authors: Antoniades Harry N
Published: December 2014

Intravenous administration of partially purified preparations of rat serum “bound” insulin into hypophysectomized rats, produced hypoglycemia and stimulated the incorporation of glucose carbon into the glycogen of muscle and adipose tissue and into the fat of the adipose tissue of these animals. Intraperitoneal injections of rat “bound” insulin into intact, fed rats also stimulated the incorporation of glucose carbon into the glycogen of muscle and adipose tissue and into the fat of the adipose tissue. Rat “bound” insulin, like human, was less effective in stimulating glycogen synthesis than fat synthesis on adipose tissue, as compared with crystalline insulin.

The in vivo biologic effects of rat “bound” insulin in rats correspond to those produced by human “bound” insulin or crystalline bovine insulin. The properties of rat “bound” insulin appear to be similar to those of human “bound” insulin. Rat “bound” insulin, like human, was obtained from sera by resin adsorption and elution, was biologically active in vivo, inactive on isolated hemidiaphragm, unless adipose tissue extract (ATE) was added into the incubating medium, and unreactive with anti-insulin antisera.
Effects of Insulin upon Glucose Metabolism and Protein Synthesis by the Anterior Pituitary in Vitro
Authors: Goodner Charles J
Published: December 2014

The effects of insulin upon the metabolism of glucose by single rat anterior pituitary glands in vitro have been compared with the effects of raising the concentration of glucose in the suspending medium. The pattern of stimulation with insulin differed from that induced by increasing glucose. Insulin enhanced glucose oxidation, glycogenesis and lipogenesis out of proportion to the increase in glucose uptake.

The anterior pituitary exhibited relative insensitivity to insulin in vitro compared to muscle and adipose tissue. Stimulation of glucose metabolism was detectable at 1,000 uU. insulin per milliliter medium, and maximum stimulation occurred between 0.1 and 1.0 U. per milliliter. Insulin sensitivity was not altered by fasting. The effect of insulin was attenuated upon substituting phosphate for bicarbonate as buffer in the incubation medium.

The incorporation of glycine C-14 into tissue protein was stimulated by insulin and this effect was undiminished in the absence of glucose in the medium. The incorporation of C-14-alpha-amino-isobutyric acid from the medium into the anterior pituitary was greater than that reported for rat diaphragm and was not affected by insulin.

The data indicate that insulin could potentially affect hormonogenesis in anterior pituitary through stimulation of protein synthesis. The cell types responsive to insulin and the physiologic consequences of insulin activity upon the anterior pituitary remain to be established.
Intravenous Glucose Tolerance Test in Pregnancy in Women Living in Chronic Hypoxia
Authors: Calderón Rolando , Llerena L Alberto , Munive Leopoldo , Kruger Francisco
Published: December 2014

Rapid intravenous glucose tolerance tests have been performed in women living at high altitude in an environment of chronic hypoxia (average values: barometric pressure 445 mm. Hg, alveolar p02 46.0 mm. Hg, arterial p02 45.1 mm. Hg). The hypoxic group had a curve of the same shape but with lower values when compared with that of women born and living at sea level.

At sea level pregnancy modified the curve obtained when compared with that of nonpregnant women, but at high altitude pregnancy did not modify the curve. As a possible explanation a higher basal level of insulin in the high altitude group is suggested.
Studies of Glucose Metabolism Immediately Following Total Pancreatectomy
Authors: Kosaka Kinori , Mizuno Yoshiatsu , Ogata Yasuzo , Kuzuya Nobusada
Published: December 2014

Blood sugar changes were studied in anesthetized dogs before and after pancreatectomy, which was carried out in two stages, the latter being relatively atraumatic. The blood sugar remained normal for 1.5 to 4 hrs. after total pancreatectomy, then increased to the diabetic level.

Comparison of glucose tolerance before and immediately after acute pancreatectomy revealed no significant change by either intravenous or intraduodenal route.

Thus, a sudden cessation of insulin supply does not necessarily result in immediate hyperglycemia. A normal glucose tolerance appears possible temporarily in the absence of any increase in insulin secretion.
A Comparison of the Oral Sodium Tolbutamide Test and the Oral Glucose Tolerance Test in Selected Hospital Patients
Authors: Tittle C Robert , Kerr John H
Published: December 2014

Increasing use of the two-hour postprandial blood glucose test in screening for diabetes detection has resulted in an increased number of borderline oral glucose tolerance tests, and the dilemma of their proper interpretation. In spite of controlled pretest precautions, the two-hour-lag oral glucose tolerance test with fasting normoglycemia may lack specificity as an index of latent diabetes. The intravenous tolbutamide test as a supplemental test may offer greater specificity in the diagnosis of early diabetes, and a recent oral modification of this test offers added convenience and safety without sacrificing reliability.

This is a report based upon the oral test performed on a group of 105 hospital patients selected because each had an elevated second-hour blood sugar level with fasting normoglycemia on a standard oral glucose tolerance test. An abnormal oral sodium tolbutamide test was elicited in fifty-two of this group of 105, and the abnormal tolbutamide test correlated significantly with a positive family history of diabetes, an obstetrical history suggestive of diabetes, or those patients with an elevated third-hour blood sugar level on oral glucose tolerance. In only six of the 105 patients studied were the results of the oral sodium tolbutamide tests classified as borderline between normal and abnormal by the criteria of Boshell and Vecchio.

We conclude that the oral sodium tolbutamide test seems to be a valuable additional study in the appraisal of minimally abnormal oral glucose tolerance results at least in the presence of obesity, liver disease, hyperthyroidism, uremia, myocardial infarction, chronic pancreatitis, spontaneous hypoglycemia, and lymphomas and related neo-plasia representing the major disease categories in our study group.
Tolbutamide Loading in the Initial Therapy of Diabetes Mellitus
Authors: Arora Ravindra S , Hardy Patrick , Perkoff Gerald T
Published: December 2014

A controlled study has been made comparing a loading dose schedule of tolbutamide with a maintenance dose schedule in the initial therapy of fourteen patients with maturity-onset diabetes mellitus. No advantage of one dose schedule over another was found. Since hypoglycemia may occur when large doses of tolbutamide are used, these results provide supporting evidence for those who recommend use of low doses of this drug in the initial therapy of patients with diabetes mellitus.
Prolonged Hypoglycemia Following Acetohexamide Administration: Report of Two Cases with Impaired Renal Function
Authors: Alexander Ralph W
Published: December 2014

Prolonged hypoglycemia was precipitated by acetohexamide in two patients with renal failure. In one case the hypoglycemia lasted eight days after withdrawal of the drug, representing the longest recorded such reaction to the sulfonylureas. The cause for the prolonged reactions in these two cases appeared to be the renal retention of acetohexamide metabolites possessing unaltered hypoglycemia potency. A classification of the pathogenesis of prolonged hypoglycemia secondary to sulfonylureas is given and related to the two reported patients.
Assay of Insulin Antagonism by Serial Incubation of Paired Rat Hemidiaphragms
Authors: Davidson Mayer B , Goodner Charles J
Published: December 2014

A method utilizing serial incubations of paired rat hemidiaphragms has been developed. In this technic, two basal glucose uptakes and two uptakes in the presence of insulin can be determined in a single rat, thus eliminating rat to rat variations when comparing two insulin effects. This system, particularly useful for the study of insulin antagonism, was applied to the assay of the albumin-associated antagonist in various human and commercial preparations. The presence of higher concentrations of this antagonist in untreated adult-onset diabetes was confirmed in two out of three diabetic patients tested. Albumin from a third diabetic patient was stimulatory. Varying amounts of antagonism were found in the commercial albumin preparations. Evidence is presented suggesting that total bound FFA do not play an important role in the albumin-associated insulin antagonism.
Effect of Human Serum Albumin on the Glucose Metabolism of Isolated Rat Diaphragm and Its Response to Insulin
Authors: Buse Maria G , McMaster Jan , Buse John
Published: December 2014

The effect of human serum albumin prepared by Cohn method 6 on the glucose metabolism of isolated rat diaphragms was studied. In the absence of insulin 5 per cent albumin slightly inhibited glucose uptake and lactate production but not glycogen synthesis. Albumin partially inhibited the stimulatory effect of insulin on glucose uptake, lactate production and glycogen synthesis. The insulin antagonistic effect of 5 per cent albumin was due in part only to increased H+ ion concentration in the medium. Albumin (1.25 per cent) did not affect glucose utilization or lactate production with or without insulin. Albumin (5 per cent) alone slightly but significantly augmented the penetration of d-xylose into “intact” diaphragms. In the presence of insulin and albumin the space of distribution of d-xylose was significantly less than with insulin alone.

The albumin preparations contained free fatty acids and citrate; however, the insulin antagonism of 5 per cent albumin could not be reproduced with palmitate or citrate. Following dialysis and lyophilization 5 per cent albumin assayed at controlled pH did not affect glucose uptake, lactate production or glycogen synthesis either in the presence or absence of insulin. The noninhibitory albumin was extracted with TCA-ethanol, dialyzed, lyophilized and assayed as above. It significantly inhibited the stimulatory effect of insulin on glucose uptake, lactate production and glycogen synthesis.

It is suggested that several factors can be associated with albumin and antagonize the stimulatory effect of insulin on muscles in vitro. These factors will have to be separated and characterized before the biological significance of the “synalbumin antagonist” of insulin can be evaluated.
Metabolism of Lactate in Alloxan Diabetic Acidosis
Authors: Steenrod William J , Prahl James W , Barron Edward J
Published: December 2014

Normal and alloxan diabetic rats were injected with DL-lactate-l-C-14, DL-lactate-2-C-14 and L(+) lactate-l-C-14 and the total excretion of radioactivity determined. The uncontrolled diabetic rat expired about 15–20 per cent less C-14-O2 than the normal animals. The diabetic animals excreted about twice as much radioactivity in the urine as the normal animals; in these diabetic animals essentially all of the radioactivity was found in glucose.

After evaluation of all the possible reasons for the difference in amount of C-14-O2 expired by normal and diabetic animals it was concluded that lactate is metabolized at essentially the same rate in both animals but that in the diabetic animal, a greater portion of the carbon atoms of lactate is incorporated into glucose and less converted to CO2.
Sulfated Insulin in Mild, Moderate, Severe and Insulin-resistant Diabetes Mellitus
Authors: Little J Alick , Arnott James H
Published: December 2014

Moloney and co-workers prepared sulfated insulin and showed it to be less antigenic and less neutralizable by antibodies than unmodified insulin. The present study compares sulfated insulin with commonly used insulins (Regular, Protamine Zinc, Lente and NPH) in twenty-four hospitalized adult diabetics. The bases of comparison were units of insulin per day, three daily blood glucose levels and urine glucose content.

In six severe, ketosis-prone diabetic patients, sulfated insulin in approximately equal doses failed to control the disease nor did the usual long acting insulins.

In four mild diabetic patients sulfated insulin had no apparent advantage over other insulins.

For nine of twelve moderate diabetic patients less or equal units of sulfated insulin provided better control.

In two insulin resistant patients sulfated insulin very greatly reduced insulin requirements (to 5 per cent and 37 per cent) and provided much better control.

Hypoglycemia was no more frequent with sulfated insulin and there were no important toxic side effects. It appears to be a promising advance in the treatment of insulin resistant diabetes and prolonging its action may further enhance its usefulness.
Sex Distribution and Frequency of Diabetic Concomitants or Complications
Authors: Danowski T S , Limaye N R , Cohn R E , Grimes B J , Narduzzi J V , Shelkrot J W
Published: December 2014

The data herein presented or reviewed indicate that the prevalence of concomitants or complications of diabetes such as hypertension, obesity, retinopathy, neuropathy, etc. may vary greatly from clinic to clinic. Though variable diagnostic criteria, observer error, ethnic or national differences may account for some of the disparity, selection of patients through death, economic factors, etc., which results in clinic rosters which are not representative of the total diabetic population also plays a role of undetermined significance. Hence definitive statements concerning the relative predisposition of males and females to concomitants or complications of diabetes must await standardization of population and criteria, data on incidence as well as prevalence, and expression of such data on a cumulative basis. Until then we can only speak of findings in limited populations because we have as yet no basis for intergroup comparisons.
Stimulation of Release of Insulin by an Extract of Intestinal Mucosa
Authors: Duprè J , Beck J C
Published: December 2014

The mechanism of action of an extract of intestinal mucosa that accelerates the disposal of glucose given intravenously in normal man was investigated. The active material is biologically distinguishable from pancreozymin, and its effects cannot be attributed to insulin, insulin-like activity, glucagon or amino acids in the preparation. The extract enhances the increase in blood-insulin concentration which occurs in response to the intravenous infusion of glucose in normal man and which has been compared with that following ingestion of glucose. No response was demonstrable in insulin-treated juvenile-onset diabetes, and it is suggested that the extract acts in normal subjects by stimulating the jrelease of endogenous insulin. It is concluded that an insujln-aecretagogue, derived from the small intestine, may be concerned in the response to ingested glucose, and that such, an agent may be present in the active extract.
Effect of Tolbutamide on Postnatal Neogenesis of the Islet of Langerhans in Mouse
Authors: Bunnag Srichitra C , Warner Nancy E , Bunnag Sirotma
Published: December 2014

Tolbutamide stimulates postnatal neogenesis of the islets of Langerhans as demonstrated by enumeration of the islets, in vivo studies and radioautography. This drug first causes transient dilatation of insular vessels and rapid blood flow, followed by de granulation of the beta cells. Reappearance of granules, proliferation of the small pancreatic ducts, formation of new islets and an increased number of small islets occur during chronic administration of tolbutamide. The implications of these findings for the management of juvenile diabetes are discussed.
Effect of Alloxan Diabetes on Cholesterol Flux into Aorta
Authors: Matsuda Ichiro , Kalant Norman
Published: December 2014

The rate of flux of cholesterol from plasma to aortic wall has been measured in normal and diabetic rats given an atherogenic diet. At any given time, there were significant linear relations between plasma cholesterol concentration and influx rate and between influx rate and aortic cholesterol concentration, These relationships altered with time in a manner to suggest the development of an inhibition to cholesterol influx. Diabetic animals had higher levels of plasma cholesterol, but the interdependencies among the three parameters noted were qualitatively the same as those of the nondiabetics, suggesting that the increased susceptibility of diabetics to the development of atherosclerosis is due to more severe hypercholesterolemia. The flux rate of cholesterol into the aorta was much higher than the net rate of cholesterol deposition, indicating that a large part of the influx is in the form of exchange with a labile pool. On replacement of the atherogenic diet by a normal diet, the plasma cholesterol fell promptly to normal while the aortic cholesterol fell more slowly and did not return to the normal level. The results applied equally to unesterified and total cholesterol and to cholesterol of whole plasma or low density lipoproteins.
Effect of Tolbutamide on “Free” and “Complexed” Serum Insulin
Authors: Gundersen Kare
Published: December 2014

Serum insulin levels have been determined in non-diabetics and non-insulin requiring diabetics during the oral tolbutamide test. Using diluted sera, with the addition of heparin to measure “free” and “complexed” insulin by the rat diaphragm insulin bioassay, there was little evidence that tolbutamide has any appreciable effect on the dissociation of “complexed” insulin by this method. Several patients appeared to have no “complexed” insulin in their sera at any time. Obese subjects had higher serum insulin levels than those of normal weight.
Arterial Fluorescein Studies in Diabetic Retinopathy
Authors: Kohner E M , Dollery C T , Paterson J W , Oakley N W
Published: December 2014

Fifteen patients with diabetic retinopathy were studied by fluorescence angiography after injections of sodium fluorescein into the innominate artery. This method allows individual capillaries to be visualized in life and restudied at intervals.

Microaneurysms were the most conspicuous feature. Many were situated on vessels at the edge of areas of capillary closure but others were located on capillaries which appeared otherwise normal. Regions of capillary closure were common and occurred even in the milder retinopathies. The areas involved ranged from about 0.1 mm. up to 5 mm. in diameter. Other capillary changes included general dilatation, shunt vessel formation and new vessel systems. Abnormalities of arterioles were seen in severe retinopathy. Three patients who had extensive destruction of the perimacular capillary bed also had occlusion of arterioles and venules surrounding the macula.

These observations are discussed in relation to the pathogenesis of diabetic retinal vascular disease.
Triamcinolone Provocative Test in Offspring of Two Diabetic Parents
Authors: Navarrete Victoriano N , Torres Isabel H
Published: December 2014

In fifty-five subjects, with two diabetic parents, and who had a previous normal glucose tolerance test, 67.2 per cent showed abnormalities when tested by a triamcinolone glucose tolerance test (54.5 per cent abnormals and 12.7 per cent suspicious). This result contrasted with an incidence of 1.6 per cent abnormal tests and an additional 1.6 per cent suspicious tests in a control group matched for age and sex.

It is suggested that the triamcinolone provocative test be further employed in the search for diabetic tendencies in suspicious or likely subjects.
Use of Chlorpropamide in the Treatment of Diabetes in Pregnancy
Authors: Douglas C P , Richards R
Published: December 2014

In an underdeveloped community there are many logistic difficulties in the control and management of diabetes mellitus. Because it often was impossible to carry out insulin therapy at home, one of us (R.R.) made early use of oral hypoglycemic drugs in the diabetic clinic at the University of the West Indies in Kingston. Since 1961 sulfonylureas have been used in pregnant diabetic patients. The present report describes the results of chlorpropamide treatment in 34 pregnant diabetic women.
Insulin-like Activity in Children as Measured by Epididymal Fat Pad Assay
Authors: Wolfe Ava J
Published: December 2014

Age-matched series of control and “latent diabetic” children were given intravenous glucose tolerance tests and sera obtained for assay of insulin-like activity (ILA). The rat epididymal fat pad method was used, measuring incorporation of C-14 of glucose-1-C-14 into both CO2 and glycogen. Glycogen yielded the lower results and the greater statistical precision.

ILA was divided into “suppressible” and “nonsuppres-eible” fractions on the basis of inactivation by a guinea pig anti-insulin serum. Extraction with acid-ethanol did not increase the “suppressible” fraction, and added very little useful information to the study.

The chief difference between the two series was the smaller response of “suppressible” ILA after glucose in the “latent diabetics” than in the controls. This difference was most marked (p < .001) at fifteen minutes when the control response was maximal. By contrast, “nonsuppres-sible” ILA was not altered by a glucose load, but the baseline level was higher in the controls (p < .05).

In the fasting state, “suppressible” ILA was higher in the “latent diabetics” than in the controls when CO2 was measured, but this difference was not seen with glycogen.

In each series, the fifteen-minute ILA response depended on the k value for rate of glucose disappearance as determined by simultaneous capillary blood glucose levels. But even when matched for similar k values, this response was greater in the controls than in the “latent diabetics.” In the controls with k values > 2.3, “suppressible” ILA attained fifteen minutes after glucose showed an upward trend with increasing age.
A Computer Program for Immunoassay of Protein Hormones, with Special Reference to Insulin and Growth Hormone
Authors: Morgan Carl R , Hardigg Jack B , Fisher Donald D
Published: December 2014

A Fortran language program suitable for use in computer processing of two-antibody radioimmunoassay data has been developed. Radioisotope counts transferred to punch-cards are automatically converted to a semilog plot of standard values from which assay values are derived and “printed out” as microunits of insulin and/or milli-micrograms of growth hormone per milliliter of serum or plasma.