bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoglycemia Due to Apparent Autoantibodies to Insulin: Characterization of Insulin-binding Protein
Authors: Ohneda Akira , Matsuda Kiyoshi , Sato Munehiko , Yamagata Shoichi , Sato Toshio 
Published: December 2014

A fifty-two year old female, admitted when unconscious, had a blood glucose level of 33 mg./100 ml. Glucose injection restored consciousness, and oral glucose loading revealed a diabetic curve. Hypoglycemic coma was not produced by tolbutamide. Total immunoreactive insulin extracted from fasting plasma ranged from 824 to 1,400 μU. per milliliter. Laparotomy did not reveal adenoma of the pancreas. The specimen of the pancreas contained 3.8 U. of insulin per gram and histologically showed an increase in the numbers of islets.
Her plasma was proved to bind 131-I-insulin by gel filtration, paper chromatography and dextran-coated charcoal methods. The binding protein was identified to be gamma globulin upon paper electrophoresis and was absorbed by anti–human globulin rabbit serum. The gamma globulin was characterized as IgG on immunoelectrophoresis with radioautography. Protein fractions from the patient's plasma, freed from insulin by gel filtration after acidification, reacted with pork, beef or human insulin, and dose response curves were depicted. With bonito insulin, however, it did not show any immunologic reaction. A positive skin anaphylaxis reaction was demonstrated in a guinea pig immunized with the patient's plasma, but no precipitation reaction was observed.
Since the patient had never received insulin injections, the results suggest that the insulin-binding protein contains antibodies which are produced against endogenous insulin.
Insulin Potentiating Action of Synthetic Peptides Relating to the Amino Terminal Sequence of Human Growth Hormone
Authors: Ng Frank M , Bornstein Joseph , Welker Charles , Zimmet Paul Z , Taft Pincus 
Published: December 2014

Various synthetic fragments of the amino terminal sequence of human growth hormone (HGH) have been studied with respect to their in vitro action on glucose uptake and in vivo insulin potentiating effects. The results show that the biologic activities so far investigated are confined to sequences containing the octapeptide, Leu-Ser-Arg- Leu-Phe-Asp- Asn-Ala.
There is also a correlation between the in vitro reversal of somantin induced inhibition of glyceraldehyde-3-phosphate dehy-drogenase by the active peptides and their insulin potentiating effect in vivo. The GAPD system provides a convenient and rapid means for monitoring such peptides, but its physiologic significance is at present in doubt.
Large doses (10 mg./kg. body weight) of the active peptide HGH 1-15 do not increase the degree of lowering of blood glucose, but prolong the effect of the peptide and depress plasma immunoreac-tive insulin (IRI) in rabbits.
The mechanism of action of the active sequence has not been established at present, and the physiological significance is not yet known.
Impotence and Diabetes: Histological Studies of the Autonomic Nervous Fibers of the Corpora Cavernosa in Impotent Diabetic Males
Authors: Faerman Isaac , Glocer Leticia , Fox Dora , Jadzinsky Mauricio N , Rapaport Mauricio 
Published: December 2014

Normal androgenic function has already been reported elsewhere as a fact in impotent diabetic males. Many of these patients show some type of visceral or peripheral diabetic neuropathy. Looking for a possible neurological origin for impotence in diabetic men, we have undertaken the present study, analyzing the autonomic nervous fibers of the corpora cavernosa of the penis by means of light microscopy.
In five autopsies of impotent diabetics, mean age 51, with an average duration of diabetes of 9.6 years, the following stainings were made: hematoxylin-eosin, P.A.S. and silver impregnations. Out of five cases, four showed morphological alterations of varying degrees (hyperargentophilia, beaded thickening, spindle shaped thickening, and argentophilic spherical swellings).
No correlations were found with diabetic microangiopathy. Only one of the diabetics did not show any lesion. The control group, five non-impotent, nondiabetic patients of similar age, did not show alterations at all.
This first study of the autonomic nervous system in the corpora cavernosa of impotent diabetics lends strong support to the idea that their sexual impotence is due to a neurological lesion of the nerve fibers that control erection.
Insulin Receptors in Human and Animal Placental Tissue
Authors: Posner Barry I 
Published: December 2014

The existence of polypeptide hormone receptors in the human placenta was evaluated by studying the specific binding of 125-I-labeled insulin, human growth hormone (hGH), human pro lac tin (hPRL) and glucagon to a defined placental membrane fraction. Only insulin showed specific binding to placental membranes. The binding of 125-I-insulin was time and temperature dependent. Its dissociation from the membrane was first order with a half time, at 24° C, of twenty minutes. Specific binding was readily observed at a concentration of 5 × 10−11 (7.5 μU./ml.). Inhibition of 125-I-insulin binding by unlabeled insulin was 30 per cent at 10−9 M, and &gt;90 per cent at 10−9 M. Desalanine insulin was equally effective in inhibiting the binding of 125-I-insulin. Proinsulin was about twenty times less effective, and desoctapeptide insulin was even less effective. Structurally unrelated polypeptide hormones were without significant inhibitory effect. Binding sites of relatively high affinity (K1 = 4.2 × 108 M−1) and low capacity could be distinguished from those of lower affinity (K2 = 0.7 × 108M−1) and higher capacity. Insulin degrading activity was shown to be present in the placental membranes. Under standard binding assay conditions, less than 20 per cent of the 125-I-insulin present was degraded. The 125-I-insulin could be eluted from the membranes and appeared intact by several criteria. Specific binding was augmented by Ca++ and other divalent cations but was unaffected by high sodium chloride concentrations. Binding was greatly reduced by pretreatment of membranes with proteolytic enzymes. Incubation with phospholipase C, RNase and neur-aminidase had relatively little effect on binding.
Insulin binding was unaffected by maternal diabetes but was reduced in membranes from early gestational placentas. There was considerable species variation in insulin binding, with the placental membranes of the guinea pig and monkey having the highest and those of the rat having the lowest binding.
The characteristics of the insulin binding sites in the human placenta are similar to those in established insulin target tissues.
Enzymes of Glucose Metabolism in Liver of Subjects with Adult-onset Diabetes
Authors: Belfiore Francesco , Romeo Francesco , Napoli Elena , Vecchio Luigi Lo 
Published: December 2014

An enzyme study was made on needle biopsy specimens of liver from thirty-two subjects with adult-onset diabetes and normal body weight and thirty-two controls. The enzyme pattern in the patients with diabetes was different from that seen with alloxan diabetes.
The activities of the two glucose phosphorylating enzymes tested were changed in opposite directions, hexokinase being enhanced and glucokinase moderately decreased. Total glucose phosphotransferase activity remained unchanged.
Phosphofructokinase had a reduced activity, which suggested depressed glycolysis, especially if considered together with the enhanced activity of the opposing enzyme, fructose-1, 6-diphosphatase. Normal activity was found for most other glycolytic enzymes, as well as for key gluconeogenic enzymes, including glutamic oxalacetic and glutamic pyruvic transaminases, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. The finding suggests normal glucose release.
Glucose-6-phosphate- and 6-phosphogluconate dehydrogenase activity was elevated. This would indicate an increased metabolism of glucose through the oxidative pathway and, therefore, increased formation of NADPH. This metabolic condition, which is known to favor fatty acid synthesis, might contribute to fatty liver changes. On the other hand, NADP-isocitrate dehydrogenase, which does not provide NADPH for fatty acid synthesis, was little changed.
Assessors of Fetal Perinatal Mortality in Diabetic Pregnancy: Analysis of 1,332 Pregnancies in the Copenhagen Series, 1946–1972
Authors: Pedersen Jøhrgen , Mølsted-Pedersen Lars , Andersen Bjørn 
Published: December 2014

In a series of 1,332 pregnancies in women with diabetes, perinatal fetal mortality varied in a statistically significant degree, with maternal factors and pregnancy complications expressed respectively, by the White and PBSP classifications. Also, mortality declined steadily over the years 1946 to 1972. Fatal congenital malformation was the most important single cause of perinatal death in recent years.
A controlled trial must take into account the year of admission as well as the White and PBSP classifications; with the prevailing low and decreasing mortality, even large centers may be unable to fulfill the requirements as to sample size within a few years. Therefore, criteria other than perinatal mortality may be needed to assess the value of changes in treatment.
An Artificial Endocrine Pancreas
Authors: Albisser A M , Leibel B S , Ewart T G , Davidovac Z , Botz C K , Zingg W 
Published: December 2014

In order to regulate the blood sugar in the intact depancreatized dog as precisely as that accomplished by its normal pancreas, specific equipment has been devised to deliver insulin or glucose continuously and establish normoglycemia both in the fasting and glucose-loaded states. A minicomputer was programmed to respond to the constantly monitored whole blood glucose by injecting appropriate insulin or glucose intravenously to maintain or restore the normal blood sugar.
Standardized glucose challenges consisting of uniform infusions of 10 mg. glucose per kg. min. for sixty minutes were applied to assess the performance of the artificial pancreas. Direct control which relates insulin dosage to the level of the circulating blood sugar results in a response to the challenge resembling mild maturity-onset diabetes both in the abnormally high blood sugar response to glucose loading and in the large amount of insulin required to effect a return to normoglycemia. In contrast, control based on projected (predicted) values of blood sugar not only prevents the abnormal rise but consumes in some cases only 10 per cent of the insulin used for the same glucose load. The performance of the system parallels that of the normal pancreas and lends support to the hypothesis that biphasic insulin responses to glucose challenges are essential for the economy of insulin and the precision of regulation seen in healthy subjects.
Plasma Proinsulin: Comparison of Insulin Specific Protease and Gel Filtration Assays
Authors: Cresto Juan C , Lavine Robert L , Fink Gloria , Recant Lillian 
Published: December 2014

Our laboratory has had a good experience using the gel filtration assay for proinsulin. Since the proteolytic enzymatic assay for proinsulin has the reported advantage of being simpler and requiring less plasma per assay, a comparison was made of the enzyme and gel filtration assays for plasma proinsulin. The proteolytic enzyme was prepared from rat muscle and a 30 to 60 per cent ammonium sulfate fraction was used. The kinetics of the enzyme were characterized with regard to substrate concentration (proinsulin and insulin), enzyme concentration, time of incubation and effect of plasma. The studies of enzyme using labeled substrates revealed identical behavior as with cold substrates. The Km for insulin was .476 × 10−6M and for proinsulin was .956 × 10−6M. Lineweaver-Burk plot showed competitive inhibition between insulin and proinsulin. A noncompetitive inhibitor of the enzyme was identified in a plasma sample from a “normal” human subject.
The plasma proinsulin assay was performed as described by Kitabchi et al. with the modification that each plasma had an internal control incubated with labeled insulin or proinsulin. It was seen that the activity of the enzyme was somewhat variable in different plasmas. In noninsulinoma samples of plasma, the per cent proinsulin varied between 0 and 72 per cent. In the insulinoma plasmas, the values were 30 to 143 per cent. Twenty-one samples were compared with the gel filtration assay for proinsulin. This latter procedure utilizes G-50 Sephadex columns with size separation of proinsulin and insulin. Enzymatic assay values appeared consistently higher but still had a degree of correlation with those obtained by column. However, the enzyme assay has significant limitations both in screening of normal subjects as well as in diagnosing insulinomas, since false high proinsulin values may be found.
Gel filtration appears at this point in time to be the most reliable method for assay of plasma proinsulin-like material.
Insulin and Glucagon Degradation by the Same Enzyme
Authors: Duckworth William C , Kitabchi Abbas E 
Published: December 2014

An insulin-degrading enzyme has been previously isolated from rat skeletal muscle and highly purified by a series of procedures including affinity chromatography on insulin-agarose. Glucagon-degrading activity was also found in each of the purification steps including the final highly purified material. Insulin- and glucagon-degrading activities were associated with the same band on polyacrylamide gel and both activities were obtained from affinity chromatography on glucagon-agarose.
Insulin- and glucagon-degrading activities could not be differentiated by the effect of sulfhydryl reagents, pH, or by heat inactiva-tion. Insulin served as a competitive inhibitor of glucagon degradation (Ki = 1.5 × 10−8M) and glucagon was a competitive inhibitor of insulin degradation (Ki = 5.3 × 10−6M).
On the basis of these studies it appears that insulin and glucagon can be degraded by the same enzyme which is found in the soluble fraction of rat skeletal muscle homogenate.
Changes in Immunospecificity and Biologic Activity of Bovine Insulin Due to Subsequent Removal of the Amino Acids B1, B2 and B3
Authors: Kerp L , Steinhilber S , Kasemir H , Han J , Henrichs H R , Geiger R 
Published: December 2014

The influence of splitting off the N-terminal amino acids B1, B2 and B3 of bovine insulin on the binding of these derivatives to antibodies raised with bovine insulin in guinea pigs and on biologic insulin activities is investigated.
In comparison with bovine insulin the standard free energies −ΔF°1 for complex formation between high affinity antibodies Ak1 and des-PheB1-insulin or des-(Phe-Val)B1-2-insulin are reduced to 77 per cent and 76.3 per cent respectively, with a further decrease to 68 per cent for des-(Phe-Val-Asn)B1-3-[PyrB4] insulin.
The standard free energy -ΔF°2 for complex formation between low affinity antibodies Ak2 and des-PheB1-insulin drops to 48.4 per cent. Further splitting off of the N-terminal amino acids B2 and B3 completely abolishes the antigen binding to Ak2.
The ability of both des-PheB1-insulin and des-(Phe-Val)B1-2-insulin to lower the in vivo blood sugar level does not differ significantly from bovine insulin, whereas the in vivo activity of des-(Phe-Val-Asn)B1-3-[PyrB4] insulin decreases to 70±7 per cent.
The in vitro biologic activity, tested on isolated fat cells, is slightly reduced to 89±9 per cent for des-PheB1-insulin, to 86±3 per cent for des-(Phe-Val)B1-2-insulin and to 68±6 per cent for des-(Phe-Val-Asn) B1-3-[PyrB4] insulin.
Management of the Diabetic with Vascular Disease
Authors: Mulholland Henry B 
Published: December 2014

Vascular disease and its devastating end-results constitute one of the major problems faced by the medical profession today. The steadily increasing duration of life, with large numbers of the population living to sixty-five years of age and over, is bringing in an era in which degeneration of all systems must constitute a challenge. The diabetic too must pay the price of living longer by being more likely to develop degenerative disease and its complications.
The remarkable contributions in the field of vascular disease during the last three decades have added to the insight into these disorders. It is commonly considered that involvement of the vascular system is inevitable in the diabetic, provided he lives long enough. One does see, however, a few individuals with diabetes of many years’ duration who seem to have escaped the ravages of time and have no demonstrable changes in their vascular tree.
That arteriosclerosis in diabetes increases with the duration of the disease is evidenced by the figures quoted by Root, who noted that this process as a cause of death increased from 17 per cent at an average age of 44.5 to 70 per cent at an average age of 65.3.
As will be discussed below, diabetics seem to have a greater incidence of arteriosclerosis and atherosclerosis than does the general population. Although these conditions appear to differ in no respect from those found in nondiabetics, nevertheless, there is evidence that certain vascular changes, particularly in the retina and kidneys, may well be peculiar to the complicated metabolic disturbance found in diabetes mellitus. In many organs of the diabetic, vascular lesions are found with special frequency. They will be more fully described as the individual anatomic units are discussed. White, who studied juvenile diabetics who had lived twenty years or more after developing the disease, noted some evidence of vascular disease in 92 per cent, an astounding figure.
Factors playing a role in this increasing incidence, such as an inheritance of a defective vascular tree, seem to have some influence. Nutrition in a broad sense, infection (which is notoriously more frequent in the diabetic), so-called toxic factors, hormone imbalance, and capillary fragility all may play a part, although one cannot justifiably accuse any one of these.
Insulin Treatment of Juvenile Diabetes Observations on the Combined Use of Intermediate and Regular Insulins
Authors: McArthur James A , Jackson Robert L 
Published: December 2014

For many years the management of diabetes mellitus at the Pediatric Clinic of the State University of Iowa has had as its objective to attain and maintain physiologic control. To accomplish this end we have found the administration of insulin on a percentage distribution basis practicable.
Under the standard conditions of quantitative diet and exercise in the hospital, we obtained normoglycemic diurnal curves when four doses of regular insulin were distributed as 35, 22, 28, and 15 per cent of the total daily dosage, the injections being given one-half hour before meals and once during the night. This pattern of distribution, in keeping with the generally acceptable three-meal plan of the child, has guided us when modifying our regimen as new types of insulin have become available. We found it impossible to attain our objective using protamine-2inc insulin. In 1944, when globin insulin with zinc was made available, we started to use it in a regimen which we had developed in our clinic. In this plan, one dose of globin insulin with zinc given one hour before the evening meal replaced the evening and night doses of regular insulin. In 1953, when NPH insulin was made available, we studied its use in place of globin insulin and observed no significant differences in the diurnal blood sugar curves for groups of well regulated diabetic children.
The purpose of this study is to present the development of a satisfactory two-injection regimen employing mixtures of an intermediate insulin and regular insulin as the morning injection and an intermediate insulin as the evening injection. The intermediate insulins employed are NPH and globin insulin with zinc.
Massive Insulin Hypoglycemia and Capillary Vascular Physiology in Man
Authors: Lovet Doust John W , Salna Maria E 
Published: December 2014

The vascular responses attending major insulin hypoglycemic reactions in man have been reviewed by Kalinowsky and Hoch, Bellak, and others, but the special role of the capillary and other small vessels has received little attention. The importance of this role is implied in the investigations made on the influence of insulin in coma-provoking doses in regard to brain metabolism, the literature on which has been reviewed by Himwich, and since the capillary system is the final common path by which energy is transferred between blood elements and tissue cells.
This paper is concerned with the acute responses of the minute vasculature of two nondiabetic human subjects receiving massive doses of insulin five times weekly, over a three-month period. The more chronic vascular effects of this sequential experience of hypoglycemia are reported elsewhere.
Diabetes Mellitus and Its Degenerative Complications: A Prospective Study of 4,400 Patients Observed Between 1947 and 1973
Authors: Pirart Jean 
Published: December 2014

This article was originally published in French in Diabete et Metabolisme (vol. 3: 97–107, 173–182, 245–256; 1977). The Editors of DIABETES CARE thank the author, and the editors and publisher of Diabete et Metabolisme for granting permission for us to print this English translation. The paper was translated by Marjorie Levin of Miami, Florida.
Part I of this translation appeared in the May–June issue of DIABETES CARE (vol. I: 168–188).
Speed Control of Multiphase Cage Induction Motors Incorporating Supply Sequence
Authors: Drozdowski Piotr 
Published: December 2014

Abstract
The subject of this paper is the control possibility of the multiphase cage induction motors having number of phases greater than 3. These motors have additional properties for speed control that distinguish them from the standard 3 phase motors: operation at various sequences of supplying voltages due to the inverter control and possible operation with few open-circuited phases. For each supply sequence different no load speeds at the same frequency can be obtained. This feature extends the motor application for miscellaneous drive demands including vector or scalar control. This depends mainly on the type of the stator winding for a given number of phases, since the principle of motor operation is based on co-operation of higher harmonics of magnetic field. Examples of operation are presented for a 9-phase motor, though general approach has been discussed. This motor was fed by a voltage source inverter at field oriented control with forced currents. The mathematical model of the motor was reduced to the form incorporating all most important physical features and appropriate for the control law formulation. The operation was illustrated for various supply sequences for “healthy” motor and for the motor operating at one phase broken. The obtained results have shown that parasitic influence of harmonic fields interaction has negligible influence on motor operation with respect to the useful coupling for properly designed stator winding.