bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Aspects of Labile Diabetes
Authors: Molnar George D , Gastineau Clifford F , Rosevear John W , Moxness Karen E 
Published: December 2014

Eighteen diabetic patients representing a spectrum from hyperlabile to stable forms of this disease were investigated under metabolic ward conditions. Hyperlabile patients had the greatest daily and hourly variation in glycosuria and the most marked ketonuria. In our hyperlabile patients, multiple daily injections of short-acting insulin proved to be the only therapeutic measure that provided significant improvement in diabetic regulation when dietary and general health measures were already optimal. In more stable patients, longer acting insulin injected less frequently was found to be satisfactory therapy if careful adjustments to individual needs were made.
Blood glucose and serum ketone-body and free fatty acid concentrations as well as qualitative estimates of glucose and ketone bodies in small samples of freshly voided urine were found to be suitable indicators of the immediate state of metabolic regulation. These parameters correlated with one another to a satisfactory degree, but they proved to be poorly correlated with measurements of urinary glucose and ketone bodies during periods of five to twenty-four hours. Quantitative analysis of individual blood samples or qualitative estimates of glucose or ketone bodies in freshly voided urine specimens proved to be unreliable indices of the patients' long-term metabolic compensation except in the most stable patients. Quantitations of urinary glucose and ketone bodiesin five, nine, and twenty-four-hour collections of urine, on the other hand, give satisfactory data to assess diabetic regulation, both as to accuracy of compensation and stability.
Production of Autoantibodies to Insulin in Man and Rabbits
Authors: Grodsky Gerold M 
Published: December 2014

To determine whether antibodies to exogenous insulin bind and inactivate endogenous insulin in vivo, technics were devised to isolate and measure directly antibody bound endogenous insulin in the presence of residual exogenous hormone in human and rabbit (leporine) serum. Insulin-antibody fractions in serum were isolated by ultra centrifugation or preferential salt precipitation, insulin was extracted by acid alcohol, and exogenous (bovine) and endogenous (human or leporine insulins) were differentially determined by immunoassay.
Insulin in the antibody fraction of normal serum is undetectable (&lt; 10μU. per ml.). In two resistant diabetic patients all measurable insulin proved to be bound to antibody. Exogenous insulin, which was 4 to 5 mU. per ml. seventeen hours after the last insulin treatment, remained elevated for three to sixteen days but disappeared after ten to twenty days. The subjects proved to be capable of secreting endogenous insulin that was almost completely bound to antibody in the serum. High concentrations of bound endogenous insulin (1 to 8 mU. per ml.) persisted for two to five weeks and levels were still elevated after fifty-four days. In immunized rabbits, only bound endogenous insulin was detectable three weeks after bovine insulin was discontinued. Levels remained high (1 to 2 mU. per ml.) for five weeks. Blood sugar was normal at all times, indicating that most of the bound insulin was biologically inactive.
In man and rabbits endogenous bound insulin decreased with declining antibody titers, hence did not serve as an antigenic stimulus sufficient to maintain antibody production.
Purified insulins, both human and leporine, competitively displaced bovine insulin-I-131 from the antibody sites of human and leporine serum respectively, though they were less effective than purified bovine insulin.
It is concluded that the administration of crystalline insulin can produce circulating autoantibodies capable of binding and inactivating large amounts of endogenous hormone in vivo.
Observations on Clinical Patterns of Diabetes Mellitus in India
Authors: Tripathy Bibhuti B , Kar Bimal C 
Published: December 2014

Several points of difference can be made between features of diabetics of the Western world and the tropical countries. In addition to a lower incidence of juvenile diabetes and diabetic coma in the tropics there is a high incidence of marked underweight among diabetics of the older age group as well as the young.
Observations on ninety-six patients at Cuttack, India, reveal that apart from a few cases of juvenile diabetes and a moderate number of elderly-obese patients there is a high incidence of atypical cases. Some of these are young and very lean but require large doses of insulin for control and are not prone to ketosis (“J”) type. Others are middle-aged and generally responsive to sulfonylurea compounds but are very lean even at onset of disease (elderly-lean type).
Division of the patients into two groups, one seen in the hospital wards and the other in the private clinics (domiciliary), makes it apparent that the unusual types of diabetics are for the most part the poorer hospital (ward) patients. Of these 39.8 per cent are “J” type and 43.7 per cent are elderly-lean types compared with zero and 4.9 per cent, respectively, in the domiciliary group.
The hospital patients have been subject to chronic undernutrition and most of them take large carbohydrate meals at long intervals, often only one a day. It is postulated that imposition of this dual stress of intermittent starvation and overload on carbohydrate metabolism may be related to the atypical patterns of clinical diabetes.
Degranulation of Beta Cells and Loss of Pancreatic Insulin after Infusions of Insulin Antibody or Glucose
Authors: Logothetopoulos J , Davidson J K , Haist R E , Best C H 
Published: December 2014

The experimental findings reported here may have some implications concerning the secretion of insulin under physiological conditions. They would suggest that at agiven level of blood glucose, the rate of insulin loss from the beta cells may be largerwhen the level of insulin in the blood is low. They would suggest too that beta cells lining the proximal portions of the islet sinusoids would secrete to a greater degree thanbeta cells lining the more distal parts of the sinusoids.
In previous experiments reported elsewhere (see reference 3) it could not be demonstrated satisfactorily that large amounts of beef insulin (30 U.) added to solutions of glucose inhibited the rate of degranulation of beta cells of the infused rats. The results of those experiments and the results with insulin-antibody, reported here, need to be reconciled. Excess circulating insulin-antibody probably keeps the concentration of free diffusible insulin at levels close to zero in the sinusoids of the islets. The mechanism facilitating beta cell degranulation may be operating effectively at extremely low concentrations of insulin. Maximal inhibition of the glucose effect may be reached very soon as the concentration of diffusible insulin rises in the sinusoids of the islets. In ratsinfused with glucose, endogenous insulin in the milieu of the beta cells might quickly reach this level so that the addition of exogenous beef insulin has no demonstrable effect.
The Extractable Insulin Content of Pancreas from Fetuses and Infants of Diabetic and Control Mothers
Authors: Steinke Jurgen , Driscoll Shirley G 
Published: December 2014

The acid ethanol extractable insulin content of pancreases from thirty-seven infants and three early fetuses of diabetic and control mothers has been measured and their islet cell histology was studied. In general there was good agreement between these two parameters.
Pancreatic insulin could be detected in one of two twelve-week old fetuses examined and in the pancreas of a fourteen-week old fetus of a diabetic mother. The remaining thirty-seven pancreases were obtained from fetuses of gestational age twenty weeks to term, nine of whom were offspring of diabetic mothers. The latter contained more insulin than the corresponding control group. The possible mechanisms are discussed; the hyperglycemic hypothesis is favored.
Glucose Metabolism in Leucocytes from Patients with Diabetes Mellitus, with and without Hypercholesteremia
Authors: Munroe John F , Shipp Joseph C 
Published: December 2014

The metabolism of glucose by the Embden-Meyerhof, pentose cycle and citric acid cycle pathways was determined in human polymorphonuclear leucocytes from control subjects and from patients with diabetes mellitus, with and without hypercholesteremia.
In controls over 85 per cent of glucose uptake was metabolized to lactic acid by the Embden-Meyerhof pathway; about 5 per cent of glucose uptake was recovered as Co2, mostly from oxidation in the pentose cycle. Minimal citric acid cycle activity, a finding which correlated well with the paucity of mitochondria in the leucocyte, was shown by the slight and similar degree of oxidation of pyruvate and acetate.
Glucose metabolism in leucocytes from diabetics differed in two respects. The per cent of glucose uptake oxidized in the pentose cycle was increased in leucocytes from all diabetics. In the insulin-treated diabetics glucose uptake and lactic acid formation were similar to controls. In contrast, glucose uptake and lactic acid formation were reduced in leucocytes from adult, latent, hypercholesteremic diabetics. Pyruvate and acetate oxidation was similar in diabetics and controls. Thus, in terms of leucocyte metabolism, hypercholesteremia in the human diabetic was correlated with reduced glycolysis and not with reduced pentose cycle activity.
Effect of Endogenous Insulin on Human Amino Acid Metabolism
Authors: Zinneman Horace H , Nuttall Frank Q , Goetz Fred C 
Published: December 2014

This study describes the effect of endogenous insulin on free plasma amino acids. The secretion of insulin was provoked by means of a standard glucose tolerance test.
Four healthy males responded by a drop in the levels of all twenty-two plasma amino acids, which were measured. In four insulin-dependent diabetics the glucose tolerance experiment effected only slight decreases in nineteen of twenty-two amino acids. Ornithine and histidine decreased significantly, whereas phenylalanine increased.
The over-all result indicates that endogenous insulin reduces the levels of the majority, if not all, free plasma amino acids.
Structural and Functional Characteristics of Neonatal Pancreas Homografts in Alloxan Diabetic Golden Hamsters
Authors: Sak Matthew F , Macchi I A , Beaser Samuel B 
Published: December 2014

The present study extends preliminary investigations on the release of insulin-like activity (ILA) by pancreatic homografts.
Neonatal pancreas was implanted into the cheek pouch of alloxan-diabetic golden hamsters maintained with insulin. Hosts were treated additionally with cortisone and tolbutamide either singly or in combination. Homografts were evaluated structurally (aldehyde fuchsin) and functionally (fat pad bioassay) at periodic intervals.
In hosts receiving insulin alone, revascularization of the homografts occurred generally by seven days and complete exocrine degeneration by thirty days. The former process was delayed by cortisone and the latter accelerated by tolbutamide but delayed by cortisone. Cortisone prevented lymphocytic infiltration while tolbutamide significantly increased the number of islets with mitotic figures.
The number of homografts with islets demonstrating ILA in vitro was increased when hosts were pretreated with cortisone and insulin one week before transplantation and tolbutamide and insulin after transplantation. Arbitrary scoring of the survival and functional capacity of the homografts indicated this treatment to be twenty-eight times more effective than treatment with insulin alone. The magnitude of ILA released per transplant was not significantly different as a result of different treatments. However, omission of tolbutamide for twelve days prior to bioassay significantly increased the number of homografts able to release ILA. This suggests that the functional deficiencies observed with uninterrupted tolbutamide treatment may have resulted from overstimulation above that occurring as a consequence of diabetic hyperglycemia.
Glucose Tolerance, Nutrition, and Diabetes in Uruguay, Venezuela, Malaya, and East Pakistan
Authors: West Kelly M , Kalbfleisch John M 
Published: December 2014

In each of four countries (Uruguay, Venezuela, Malaya and East Pakistan) where diets and other environmental factors differ greatly, the prevalence of diabetes as determined by impaired glucose tolerance was crudely estimated.
Since all subjects received glucose loads, rates of prevalence are much higher than those obtainable by certain less sensitive standard methods. In the tested subjects over thirty years of age the prevalence of “diabetes” (two-hour venous blood glucose levels greater than 149 mg. per 100 ml.) was 6.9 per cent in Uruguay (6.8 per cent for males and 6.9 per cent for females). The prevalence of impaired tolerance in this age group in Venezuela was 7.3 per cent (4.5 per cent in males and 9.4 per cent in females), while in Malaya the rate was only 3.5 per cent (4.5 per cent in males and 2.1 per cent in females). In East Pakistan impaired tolerance was present in only 1.5 per cent of this age group (1.2 per cent of males and 2.8 per cent of females). Comparable data are not available in the United States but with use of the technics employed abroad it was found that 17.2 per cent of volunteers in this age group in a Pennsylvania community had impaired tolerance.
In East Pakistan, 83 per cent of calories were derived from carbohydrate. Comparable figures were 77 per cent for Malaya, 62 per cent for Venezuela and 53 per cent for Uruguay. In East Pakistan, only 7 per cent of the dietary calories were derived from fat; in Malaya, fat accounted for 21 per cent of dietary calories, in Venezuela, 24 per cent, and in Uruguay, 33 per cent. In East Pakistan only 29 per cent of dietary fat was animal fat. In Malaya, Venezuela, and Uruguay, comparable figures were 30, 35 and 62 per cent, respectively.
In Uruguay, 34.4 per cent of the subjects were “obese” (30 per cent or more over “standard” weight), and in Venezuela 14.8 per cent were obese. In contrast none of the subjects from Malaya (566 persons), or East Pakistan (519 persons), was obese by these criteria.
In Venezuela and Uruguay there was an association between the prevalence of diabetes and both parity and a history of large babies.
Hyperosmolar Nonketotic Diabetic Coma
Authors: Jackson W P U , Forman R 
Published: December 2014

Twelve cases of diabetic hyperosmolar coma without ketosis are described in ten patients. Seven of these were complicated by other illnesses. Seven died, but in five death Was probably not due to the hyperosmolar state. One had a pancreatic carcinoma; others in the literature are reported to have had pancreatitis.
The hyperosmolarity in this syndrome is due to either gross hyperglycemia or hyperelectrolytemia or both. Focal or generalized seizures occur in some cases. Very hypotonic neutral fluid in Targe quantities appears to be essential in the treatment in addition to insulin.
No case has been reported in a young person and all patients have been either new diabetics or their diabetes has been previously mild, and remains mild in those who live.
The absence of ketosis is possibly due to a block in the metabolic pathway of fatty acid breakdown. Hyperosmolarity must also be considered as a factor in the coma associated with ordinary diabetic ketosis.
Augmented Insulin Secretion Due to Growth Hormone: Stimulating Effects of Glucose and Food in Dogs
Authors: Campbell James , Rastogi Krishna Sudha 
Published: December 2014

In iinanesthetized dogs, portal vein (PV) blood was repeatedly sampled by means of an indwelling cannula, simultaneously with blood from a superficial vein (SV), for determination of insulin by two-antibody immunoassay. Under control conditions, and in the postabsorptive state, mean serum insulin in the SV was 31 μU. per milliliter, and the PV/SV ratio was about 2. Following intravenous injection of 1 gm. of glucose per kilogram of body, serum insulin rose in 15 to 30 min. to peak values that were higher in the PV, and regressed to normal in 60 to 120 min. Growth hormone, 2 mg. per kilogram of body, injected daily for six to thirteen days, (1) increased PV and SV “fasting” serum insulin to the maximum of tenfold; the effect was found after one day of injection, was maintained during injection, and returned to normal within four days of ceasing injection; (2) caused a further increase in serum insulin, in 100 min. following a meal, to a greater extent in the PV than in the SV; and (3) enhanced the rises in serum insulin in PV and SV following intravenous injection of glucose, to maxima of nine- and sixfold, respectively; these rises were prolonged and the rates of regression regression of serum insulin from the peak values were reduced. Similar effects of growth hormone treatment were found in dogs under anesthesia at the time of glucose infusion. It is concluded that, during the treatment of several days, growth hormone caused continuously maintained increase in insulin secretion with enhanced secretion in response to a meal, and to the injection of a standard load of glucose.
Further effects of growth hormone on serum were: (a) free fatty acid levels rose promptly, and remained above normal; (b) glucose tended to increase; (c) the insulin/glucose ratio increased—the values were consistently reater in the PV than in the SV; and (d) in response to the glucose load, the rate of regression of serum glucose was reduced. The insulin/glucose ratio tended to remain stable at the particular “fasting” value, following glucose injection, both under the control conditions and during growth hormone treatment. This evidence indicates that growth hormone caused readjustment of the homeostatic control of the pancreatic islets such that, at any particular level of glucose in the blood, insulin was secreted at a higher rate.
Studies on Experimental Insulin Immunity: I. Dynamics of Insulin Immunity in the Guinea Pig
Authors: Horino Masaharu , Yu Shiu Yeh , Blumenthal Herman T 
Published: December 2014

Insulin half life and the formation and characterization of the insulin-binding antibodies have been studied in the guinea pig both in vivo and in vitro. The antigen-antibody complexes have also been studied utilizing cellulose column electrophoresis and Sephadex G-200 column filtration. In addition, a quantitative assay procedure for insulin-binding antibodies has been employed.
In normal guinea pigs the injected insulin-I-125 is carried by at least two serum proteins, presumably albumin and an α. globulin, or more specifically 4.5S and 19S proteins. In immune animals the insulin-antibody complexes are represented by a single peak in the (β-γ globulin region on column electrophoresis; they are distinguishable from the uncomplexed antibodies which are 7S γ1 and 7S γ1 globulins. The precipitating insulin antibody also appears to be a 7S globulin. Moreover, the insulin-antibody complexes occur as a single component in the 19S fraction on Sephadex G-200 filtration, and if the complex were a single molecule it would have a molecular weight equivalent of about 630,000.
During the immunization process the insulin binding antibody titer increases progressively in association with an elevation of 7S globulin. In most animals during the early stages of immunization the molecular weight of the antibodies appears to be exclusively of the 7S globulin type; however, in two of seven animals there was, in addition, a small amount of insulin antibody of 19S globulin type early during the immunization period.
The purpose in estimating a molecular weight equivalent of the insulin-antibody complex relates to the possibility that the distinctive features of the angiopathies of diabetes may depend upon certain physicochemical characteristics of this complex.
Electron Microscopy of the Pancreatic Islets of the Rat: Effects of Prolonged Insulin Injections
Authors: Logothetopoulos John 
Published: December 2014

The electron microscopical changes of the pancreatic islets of rats were studied during the phase of transient diabetes and during recovery, following a prolonged period of insulin injections.
The most characteristic changes, besides the severe degranulation of the beta cells, were the “inactivity” of the Golgi complex and the absence of special spheroidal bodies from its vicinity. Evidence is presented that these satellite bodies may represent pregranules. Differences in the formation of granules in the Golgi area of the alpha, beta and acinar cell are illustrated and discussed.
Experimental Diabetes in Pregnant Mice: Prevention of Congenital Malformations in Offspring by Insulin
Authors: Horii Kin-ichi , Watanabe Gen-ichi , Ingalls Theodore H 
Published: December 2014

The main purpose of these experiments was the prevention of congenital malformations in offspring of alloxan-diabetic mice by insulin injections administered during pregnancy. The optimum dose of insulin and timing of its administration are described for mice made hyperglycemic by injection of alloxan of 80 mg. per kilogram of body weight.
Copulated female mice were given alloxan intravenously on the fourth day of gestation, followed by 0.4 units of Lente insulin every twelve hours beginning thirty to thirty-six hours after alloxan injection, and continuing until the sixteenth day of gestation. The control group was given only the alloxan injection on the fourth day of gestation. Pregnant mice were sacrificed on the nineteenth day of gestation; fetuses were removed by laparotomy and examined for external defects and skeletal deformities.
In fifty successful pregnancies treated with insulin, only one fetus (0.2 per cent) of 472 was malformed with a cleft palate; in fifty successful pregnancies given alloxan alone fourteen or 28 per cent of mice had one or more malformed fetuses. Altogether, twenty-two or 5.0 per cent of 437 fetuses in the latter group had malformations which included craniorhachischisis (seven fetuses), cleft palate (six fetuses), club foot (five fetuses), spina bifida, anencephalus, open eye, microphthalmia and skeletal deformities in one or more fetuses. The difference between the alloxan group and insulin treated group in the number of mothers having malformed fetuses, and in the number of malformed fetuses produced was statistically significant according to the chi-square test with a probability level of less than 0.01. In the alloxan group, increased body weight associated with advancing pregnancy was less advanced in mice having malformed fetuses than in those having normal fetuses. The foregoing tendency was also statistically significant with a probability level less than 0.01. However, no appreciable correlation was observed between the magnitude of hyperglycemia of mother mice and the frequency of fetuses with congenital malformations.
Combined Use of Regular and Crystalline Protamine (NPH) Insulins in the Treatment of Severe Diabetes
Authors: Oakley Wilfrid , Hill David , Oakley Nigel 
Published: December 2014

The use of twice daily injections of regular and extended action insulin mixtures, originally described in 1937, is revived and Crystalline Protamine Insulin (NPH) is proposed as the most suitable extended action insulin at present available for use in conjunction with Regular Insulin.
It is suggested that, in severe diabetes, the physician should aim at achieving a blood glucose of below 150 mg. per 100 ml. before breakfast, lunch and supper, and at bed time. This standard of control has been sought in ten pregnant diabetics treated in hospital with twice daily injections of regular + NPH insulin mixtures, and blood sugar results are reported. Experience with the same regimen in 162 diabetic clinic outpatients is also described.
Practical aspects of treatment by twice daily Regular + NPH Insulin mixtures are discussed; it is concluded that this regimen provides a good, and probably the most widely applicable, method at present available for the treatment of severe diabetes. It is sometimes possible to omit one or more of the four insulin dose components of the regimen.