bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin-like Activity in Serum of Normal and Diabetic Subjects: Results Obtained with Dual Assay Measuring Conversion of C-14 Glucose to CO2 and to Lipid in Rat Adipose Tissue
Authors: Alp Haluk , Recant Lillian , Kilo Charles , Eggeman Joanne , Koch Mary B 
Published: December 2014

Epididymal fat pad assays of insulin-like activity in plasma of normal and diabetic subjects have been carried out. When conversion of l-C-14 glucose to C-14-O2 was used as a measure of ILA, diabetics revealed elevated fasting levels, and adult diabetics showed an exaggerated ILA response to glucose loads. Juvenile-type diabetics had lower levels of ILA than the adult diabetics and responded less well to glucose.
When the measure was the conversion of 6-C-14 glucose to lipid, no elevation in fasting ILA was found in diabetics. Evidence was obtained indicating that elevated levels of NEFA may inhibit the effect of insulin on adipose tissue with respect to fat synthesis from glucose and not CO2 production.
Possible explanations for the discrepancy in the two ILA parameters are discussed.
The Relation Between the Growth and Diabetogenic Effects of the So-Called Growth Hormone of the Anterior Pituitary
Authors: Levine R , Luft R 
Published: December 2014

The accumulated evidence in the literature since 1930 reveals that pituitary extracts rich in “growth hormone” exert powerful diabetogenic effects. It has not been possible thus far to separate these two activities as belonging to two distinct molecular species. However, an analysis on broad biological principles makes it most probable that two hormonal entities compose the so-called growth hormone fraction. The somatotrophic component (STH) would be expected to exert the following actions: (1) promote protein synthesis (together with insulin); (2) cause orderly proliferation of epiphyseal cartilage; (3) lead to increased insulin liberation from B cells. The total effect would consist of growth in bodily length and enhanced protein synthesis. The diabetogenic component (here called adipokinetic .AK) would play its role in: (1) liberating fatty acids from adipose tissue, thus shifting cellular metabolism to the utilization of fat, whenever there develops a relative scarcity of carbohydrate. This shift would inhibit glucose use and lead to insulin resistance, ketone production, etc.
This analysis is presented in order to stimulate experimental approaches for testing the validity of either the “one” or “two” factor hypothesis of the pituitary growth hormone fraction. Available experimental evidence is not adequate nor sufficiently convincing for unequivocal decision.
Sugar Consumption in Vitro of the Muscle Tissue of Diabetic Patients
Authors: Magyar I , Lehoczky D , Márton I 
Published: December 2014

The sugar consumption of healthy pieces of rectus muscle incubated in normal plasma and in an insulin medium is almost identical with the sugar uptake of rat diaphragm.
The sugar consumption of healthy pieces of human rectus muscle is identical in both normal plasma and in those of our insulin-resistant diabetic patients. In four out of our five insulin-resistant diabetics, the rectus muscle pieces consumed none or only a minimum quantity of glucose when incubated in either a healthy human plasma, plasma from the diabetic patient supplying the muscle sample, or in a medium containing a known quantity of insulin.
Failure of Prolonged Sulfonylurea Administration to Enhance Insulogenic Response to Glycemic Stimulus
Authors: Seltzer Holbrooke S , Allen E William , Brennan Mildred T 
Published: December 2014

The effect of chronic administration of sulfonylurea compounds on the insulogenic responsiveness of beta cells was studied in normal dogs who received hypoglycemia-maintaining dosages of tolbutamide daily for several weeks. Insulin concentration in pancreaticoduodenal venous blood was measured during infusion of glucose at a rate causing physiologic increase in arterial glucose concentration.
Neither fasting plasma insulin level nor its enhancement during progressive hyperglycemia was significantly greater in tolbutamide-treated animals than in the control group.
The data indicate that prolonged exposure of nondiabetic canine beta cells to effective concentrations of sulfonylurea does not increase their insulin-secretory responsiveness to glycemic stimulus. Whether these agents impinge similarly or differently upon diabetic human islets awaits elucidation.
It was parenthetically observed that dogs treated with tolbutamide for several weeks required more than twice the usual amount of Nembutal to maintain surgical anesthesia.
Neurologic Disorders of Diabetes Mellitus: Part I of a Two-part Review
Authors: Colby Anthony Owen 
Published: December 2014

Neurologic disorders are a common and often disabling aspect of diabetes mellitus. Pain and sensory disturbances, weakness and paralysis and symptoms of autonomic dysfunction may be experienced by the diabetic patient.
Although neurologic disorders have been noted in association with diabetes mellitus for many years, knowledge concerning this group of disorders is quite incomplete. Terminology used in discussing them is often vague and inconsistent. There is no accepted method of classification. Pathologic studies are incomplete and inconclusive. A great variation in clinical manifestations creates difficulties in diagnosis as well as in pathophysiologic interpretation. Numerous papers have discussed the theories of pathogenesis of these disorders, yet none has answered the basic question.
This report is a review of a major portion of the literature on the subject. Emphasis is placed on the theoretical as well as practical aspects of these disorders, as their relationship to the disease state of diabetes mellitus is unique and important. These disorders must be explained in a final analysis of diabetes mellitus. Deficiencies exist in the present state of knowledge, but a solid basis for future study has been established.
The Banting Memorial Lecture 1965: Some Current Controversies in Diabetes Research
Authors: Berson Solomon A , Yalow Rosalyn S 
Published: December 2014

Among the disputed questions considered in this presentation are (1) Relationships between a) the known metabolic abnormalities in diabetes and the development of microangiopathy, and b) insulin antibodies and nodular glomerulosclerosis; (2) Sensitivity to insulin and availability of insulin in idiopathic diabetes mellitus and in other conditions associated with impaired glucose tolerance; (3) The role of pituitary growth hormone in the etiology of idiopathic diabetes; (4) The status of “bound insulin,” ILA, etc.; and (5) The identification of the “synalbumin” insulin antagonist as the B chain of insulin.
Also included are the presentation of data on insulin and growth hormone-secretory responses to glucose loading in obese and nonobese diabetic and nondiabetic subjects and a discussion of the interrelationships among the peptide hormones, glucose and free fatty acids in blood.
Light and Electron Microscopy of Prednisolone-induced Nephropathy in Rabbits
Authors: Ogilvie Robertson F , Sabour Mohammed S , Home Norman W 
Published: December 2014

Three adult rabbits given 1 mg. prednisolone intramuscularly four times weekly for twelve weeks developed glycosuria and albuminuria, and became weak and flaccid.
Light and electron microscopy reveals a variety of changes in the kidneys of the treated rabbits. By light microscopy, the glomerular tufts show congestion, capillary aneurysms, eosinophilic foci and cellular loss; Bowman's space may contain blood and other elements; the cells lining Bowman's capsule are sometimes degenerated or necrotic; and the tubules may exhibit fatty infiltration, intracytoplasmic hyaline droplets, an increase of acidophile cells in the collecting segments, cellular necrobiosis and necrosis and, like Bowman's space, a content of blood and other substances. By electron microscopy, the glomerular tufts show two types of abnormal foci; one apparently results from proteinous occlusion of one or more degenerated capillaries such as may be normal in size and shape or dilated and locally collapsed, and the other consists in an axially located intermingling of basement membrane-like material and unusually osmiophilic endothelial cytoplasm; apart from such foci the podocytes may exhibit hyaline droplets, vacuolation, intense osmiophilia or loss of substance, while the endothelial cells are sometimes abnormally electron dense and vacuolated; the cells lining Bowman's capsule may also be unusually osmiophilic and deposits of plasma-like material are occasionally noted in Bowman's space; the tubular changes include intracytoplasmic hyaline droplets, luminal debris and dilatation of the collecting tubules, but these are overshadowed by necrosis of the tubular cells, particularly in the collecting series.
The experimental renal findings are considered in relation to human diabetic glomerulopathy.
Studies on Salicylates and Complement in Diabetes
Authors: Powell Elinor D U , Field Richard A 
Published: December 2014

Increased levels of complement have been found in diabetic patients, being often more marked in young patients with proliferative retinopathy. Neither duration of diabetes nor the giving of insulin was associated with any particular alteration of complement levels. Acetylsalicylic acid was effective in suppressing complement in vitro in all instances, but to a greater extent in the younger, more severely affected patients.
These findings are discussed and related to mechanisms in production of retinopathy.
Interrelationship of Glucagon, Insulin and Glucose: The Insulinogenic Effect of Glucagon
Authors: Samols Ellis , Marri Germano , Marks Vincent 
Published: December 2014

Glucagon in doses of 0.25 or 1.0 mg. was injected rapidly, intravenously, into healthy normal subjects. There was a striking rise in arterial immunoreactive insulin levels within one minute of the start ot the injection before any change in arterial glucose concentration occurred Plasma insulin levels reached their peak within ten minutes and began to fall thereafter. In contrast, blood glucose levels were highest twenty to thirty minutes after the injection. A second glucagon injection during the hyperglycemic phase produced a larger rise in plasma insulin than the first. During constant infusions of smaller amounts of glucagon, the insulinogenic effect of glucagon was usually only apparent if blood glucose levels were raised.
The effect of consecutive forty-minute intravenous infusions of glucagon (10μg./min.), glucose (0.5 gm./min.) and a glucagon-glucose (5μg. and 250 mg./min., respectively) on plasma insulin and arterio-venous blood glucose differences in six healthy normal subjects was studied. Plasma insulin levels were two to five times higher during glucose infusions alone, despite similar peak arterial blood glucose levels during the infusions. Similar results were obtained in other subjects during separate infusions of glucose and glucagon. Total body glucose clearance, judged by the rate of fall in arterial blood glucose levels, was faster after glucagon- than after glucose-induced hyperglycemia. Forearm A-V blood glucose differences were not obviously greater during glucagon, in spite of the higher plasma insulin levels, than during glucose infusions.
Possible reasons for the failure of forearm A-V blood glucose differences to reflect accurately total peripheral glucose assimilation under these experimental conditions are discussed, and it is suggested that the co-existence of hyperglucagonemia and hyperinsulinemia may tend to favor incorporation of glucose into adipose tissue rather than muscle.
Plasma glucagon levels were measured by immunoassay and the half-life was about ten minutes.
The results provide evidence of a direct effect of glucagon upon insulin secretion. The suggestion is made that the insulinogenic effect of glucagon is physiological importance and is due to accelerated intra-β-cell glycogenolysis.
A Simplified Quantitative Enzymatic Procedure for Glucose in Urine
Authors: Weatherburn M W , Logan J E 
Published: December 2014

A simplified resin treatment for removal from urine of substances which inhibit the glucose oxidase peroxidase system of analysis of glucose is described. The original technic designed for AutoAnalyzer use has been modified for a manual procedure. The cost of enzyme reagents and resin has been minimized by use of micro proportions.
The enzymatic principle for determination of glucose in blood, serum and plasma is well established. Application of the glucose oxidase procedure to urine has been more limited, mainly due to the necessity of removing inhibitory substances from urine. Removal of these substances by adsorption, using a mixture of activated charcoal and Lloyd's reagent (hydrated aluminum silicate), has been found more satisfactory than the use of either component singly. The ingredients must be carefully adjusted because it is known that charcoal itself adsorbs glucose. Treatment of urine with resin has been described by Salomon and Johnson, and has been simplified for use with the enzymatic procedure on the AutoAnalyzer in our laboratory. Although automated procedures are becoming more widespread in use, there is still, and undoubtedly always will be, a need for simplified manual methods. Consequently the technic for the removal of inhibitory substances by means of a mixed bed resin has been investigated for adaptation to a manual glucose oxidase method. In this investigation we have found that the proportion of specimen to enzyme reagent may be adjusted so that ultramicro quantities of specimen may be assayed efficiently and conveniently. Precalibrated capillary tubes, 20 lambda volume, were extremely convenient to use and gave reproducible results. An economical amount of enzyme reagent (1 ml.) gave satisfactory photometric sensitivity. This simplification of the enzymatic procedure should help to make more practicable a method specific for urinary glucose.
Body Glucose Kinetics in Nondiabetic Human Subjects after Phenethylbiguanide
Authors: Searle G L , Schilling S , Porte D , Barbaccia J , De Grazia J , Cavalieri R R 
Published: December 2014

The kinetics of body glucose turnover have been investigated using uniformly labeled glucose in nondiabetic human subjects who have received oral phenethylbiguanide (DBI).
It is shown that phenethylbiguanide significantly accelerates the turnover of glucose in the nondiabetic subject. It is postulated that this increase in turnover (increased supply as well as increased uptake) probably accounts for the lack of hypoglycemic action of this drug in the nondiabetic human.
In several subjects a multi-exponential glucose specific activity time curve was observed. We suggest in the light of the behavior of this curve following insulin administration that the deviation from the single exponential curve is the result of extensive recycling of the C-14 label (of glucose) into the glucose pool.
Lipoatrophic Diabetes
Authors: Hamwi George J , Kruger Fred A , Eymontt Michael J , Scarpelli Dante G , Gwinup Grant , Byron Richard 
Published: December 2014

A fifteen-year-old girl with classical lipoatrophic diabetes has been studied intensively for over a year. Plasma insulin level was at the upper range of normal in thefasting state, but the insulin response to a glucose load was delayed and suboptimal. No excess of growth hormone was demonstrated. Plasma disappearance of insulin-I-131 was normal. Substances with potent lipid mobilizing activity and insulin antagonism were found in the urine.
Effects of altering periodicity of meals, increase of calories, addition of insulin, insulin plus an oral hypoglycemic agent, insulin plus a corticosteroid and insulin plus an anabolic agent have been observed. It was established that a 2000 calorie intake divided into three to ten equal feedings per day was effective in lowering the hyperlipemia and hyperglycemia. Concomitant administration of insulin and prednisone produced normoglycemia and a progressive and marked rise of all blood lipid fractions.
Light and electron microscopy of skin biopsy showed a complete absence of the typical signet-cell type adult fat cells in the subcutaneous tissue, but cells containing numerous minute fat droplets, resembling immature fat cells, were seen. Renal biopsy revealed changes characteristic of Kim melstiel-Wilson's disease.
Although the source of the substance with lipid mobilizing activity found in the patient's urine remains conjectural, it is postulated that this substance promotes rapid hydrolysis of triglycerides to fatty acids and glycerol thereby inhibiting the accumulation of triglycerides in adipose tissue. Excessive fatty acid mobilization leads to insulin resistance and interferes with peripheral glucose utilization.
Skeletal Muscle Blood Flow in Diabetic Patients Determined by Intramuscular Injection of Xenon-133
Authors: Munck Ole , Lindbjerg Ib F , Binder Christian , Lassen Niels A , Trap-Jensen Jens 
Published: December 2014

1. The clearance of the radioactive inert gas xenon-133 injected intramuscularly was studied in healthy subjects and in diabetic patients. By contrast with Na-24 or I-131 ions, xenon-133 diffuses freely across cell membranes, and local muscle blood flow (MBF) can therefore readily be calculated in milliliters per 100 gm. per minute from the xenon-133 clearance rate.
2. The maximal MBF after work during ischemia and the time from release of cuff pressure to maximal reactive hyperemia were measured in nondiabetic and in diabetic subjects without symptoms of arterial disease in the legs. Half of the diabetic subjects had neuropathy.
3. The maximal MF was normal in the diabetic subjects with neuropathy as well as in those without neuropathy.
4. The most significant finding was that the maximal reactive hyperemia sets in more quickly in diabetic subjects with neuropathy than in those without neuropathy, who behaved like the healthy subjects. This pathological hyperemia reaction may be due to an abnormally high filling pressure, increased rigidity of the vessel walls, or to a combination of both factors.
Effects of Fat Mobilization on Liver Acetate Metabolism
Authors: Bewsher P D , Tarrant M E , Ashmore J 
Published: December 2014

In insulin deficiency, release of FFA from adipose tissue and increased mobilization of lipids to the liver are followed by excessive ketone body production and a reduction in the incorporation of C-14 from labeled acetate into fatty acids. These changes in liver metabolism may not be related to insulin lack per se, but rather due to a direct effect of an accumulation of lipids or acyl-CoA esters in the tissue. The effect of lipid mobilization was investigated using dichloroisoproterenol (DCI), an adrenergic blocking agent, which has been shown to raise the plasma FFA level in anesthetized dogs with no significant effect on the blood sugar and no apparent effect on plasma insulin levels. In vitro studies have shown that DCI does stimulate FFA release from adipose tissue of the rat or the dog, at a concentration of 10-5 molar, but will block the release normally produced by catecholamines if the concentration of DCI is 10-3 molar. The rapid and sustained elevation of plasma FFA level obtained in the rat following I.P. injection of DCI (50 mg./kg.) over six hours led to an increase in total liver lipids by about 15 mg./gm. liver weight, a 50 per cent increase in ketone production by liver slices and a rise in blood ketone level. Fatty acid synthesis from 2-C-14 sodium acetate was reduced to 25 per cent of the control.
An injection of insulin given to the DCI-treated rats one hour before sacrifice, and sufficient to produce hypo-glycemia, reduced the plasma FFA level to normal, but did not influence incorporation of labeled acetate into fatty acids by the liver slices, or the blood ketone level.
The results suggest that mobilization of lipids is sufficient to produce changes in liver metabolism similar to those occurring in acute insulin deficiency.
Effect of Insulin on the Formation of Glycogen by the Mouse Diaphragm in the Presence and Absence of Glucose: A Preliminary Report
Authors: Moody A J , Felber J P 
Published: December 2014

The incubation of mouse hemidiaphragms in Krebs' buffer containing insulin, but no glucose, results in a stimulation of the formation of glycogen by the tissues; this stimulation is proportional to the concentration of insulin in the range 0 to 100 μU./ml.
The glycogen formed by mouse hemidiaphragm during incubation in buffer which contains insulin and (U. C-14) glucose, consists of a labeled and an unlabeled component. The total glycogen, the labeled glycogen and the unlabeled glycogen are all increased by an increase in the concentration of insulin in the incubation medium. Partial fractionation on a column of Sephadex G-200 of glycogen formed by hemidiaphragms incubated in the presence of (U. C-14) glucose with or without insulin, reveals that glucose is incorporated in the smaller glycogen molecules, whereas the larger glycogen molecules are, to a large extent, derived from an unlabeled precursor.
Observation of Medication Errors Made by Diabetic Patients in the Home
Authors: Watkins Julia D , Roberts Doris E , Williams T Franklin , Martin Dan A , Coyle Virginia 
Published: December 2014

Observations for accuracy in carrying out prescribed medication regimens were made at home on two groups of diabetic patients. The first group included sixty patients (all taking insulin and cared for in two university clinics), and the second 102 patients (fifty-five taking insulin and fortyseven taking oral hypoglycemic agents) cared for in two university clinics, a voluntary hospital clinic, and twentytwo different private practices.
Fifty-eight per cent of 115 patients taking insulin made dosage errors. “Potentially serious” errors, i.e., those in which the measured dose differed from the prescribed dosage by 15 per cent or more, occurred in 35 per cent. In the first group, seven of thirty-four patients (21 per cent) using the U40-U80 “convertible” syringe measured either half or twice the prescribed dose through use of the wrong scale. Rates of error were similar in clinic and in private patients. The frequency of insulin errors increased with duration of known diabetes.
Among forty-seven patients taking oral drugs, 23 per cent made “potentially serious” errors, and 26 per cent reported missing one dose or more per month.
The findings indicate the need for more extensive knowledge of what the diabetic patient does at home, for seeking the reasons for his behavior, and for finding ways to achieve sustained-improved performance.
Effects of Hypokalemia on Carbohydrate and Lipid Metabolism in the Rat
Authors: Spergel Gabriel , Schmidt Philip , Stern Alan , Bleicher Sheldon J 
Published: December 2014

A study has been made of the effect of hypokalemia on carbohydrate and lipidmetabolism.
Forty-two male Wistar rats, divided into three groups, were fed a low-potassium diet for two weeks. One group was injected with saline and fed a diet and drinking water supplemented with potassium, a second group was injected with desoxycorticosterone acetate (DOCA), while the third group was DOCA-treated and given potassium supplement. One week after the last injection, intracardiac glucose tolerance tests were performed, and blood and tissue specimens obtained for potassium, insulin, glucose, free fatty acids (FFA), and glycogen.
Hypokalemia, successfully induced by this regimen, was associated with: (1) retardation of growth; (2) increased liver and muscle glycogen; (3) no change in liver potassium; (4) increased fat potassium; (5) decreased muscle potassium; (6) elevation of fasting, and one- and two-hour post-glucose blood sugar concentrations; (7) no change in rate of early rapid disappearance of injected glucose; (8) no effect on fasting or post-glucose plasma FFA levels; and (9) no effect on mean fasting or post-glucose insulin levels, but a reduction in differential insulin response after glucose.