bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Reproducibility of the Oral Glucose Tolerance Test
Authors: McDonald Glen W , Fisher Gail F , Burnham Clinton
Published: December 2014

Results are presented of a study undertaken to explore the reproducibility of the 100 gm. oral glucose tolerance test. Over 400 male volunteers from an institutional population, who were not known to be diabetic, participated in a program which included a series of six tests for each individual over a period of one year. Ten men were tested daily, and each retested at intervals of approximately two months. Bloods were drawnat fasting, one, two and three hours after the administration of a 100-gm. glucose drinkand duplicate determinations were obtained on the Auto- Analyzer. Average blood glucose levels for the total group remained stable over time. However, blood glucose levels for individuals varied considerably. On single tests, some of the men exhibited borderline or diagnostic test readings, but in no case was this consistent over all tests. Some of the factors which contribute to individual variance are considered briefly. Implications of the data on interpretation of the results of oral glucose tolerance tests are presented.
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.
Subcutaneous Lipomas at Sites of Insulin Injection: Report of a Case
Authors: Tranquada Robert E
Published: December 2014

A thirty-eight-year-old female diabetic is described who bears symmetrical lipomas at the sites of insulin injection, which have persisted for twenty-six years. Incubation of biopsy specimens of adipose tissue from one of the lipomas compared with that of adjacent normal subcutaneous adipose tissue revealed an increase in baseline rates of oxidation of both glucose-1 and glucose-6-C-14 to C-14-02 by the lipoma tissue, as well as greater incorporation of C-14 into fatty acids. These parameters were not influenced by added insulin in the normal tissue, but were greatly stimulated in lipoma tissue. The lipoma tissue was clearly converting labeled glucose to fatty acid more efficiently than the normal tissue.
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.
Studies on the Perfused Rat Liver: II. Effect of Glucagon on Gluconeogenesis
Authors: Garcia Antonio , Williamson Joseph R , Cahill George F
Published: December 2014

In vitro studies using the isolated perfused liver from fasted rats have demonstrated increased glucose production in the presence of glucagon. The incorporation of C-14-labeled alanine into glucose was increased, as was production of urea, suggesting a primary effect of glucagon in stimulating gluconeogenesis. Time studies showed this effect to occur in ten to fifteen minutes. Incorporation of pyruvate and lactate C-14 was also increased, as was that of HC-I4-O3.
Forearm Skin Capillaries of Diabetic, Potential Diabetic and Nondiabetic Subjects: Changes Seen by Light Microscope
Authors: McMillan Donald E , Breithaupt David L , Rosenau Werner , Lee John C , Forsham Peter H
Published: December 2014

Light microscopic examinations were carried out on sections of skin from thirty diabetic and 101 control subjects. Examination of the periodic acid-Schiff stained material in a blind study revealed an abnormality in sixteen of the thirty diabetics and seven of the 101 controls. The abnormality is a hyalinization of the normally fibrillar area external to the endothelial cell of the dermal capillaries. Among the diabetics, the abnormality was seen more frequently in juvenile diabetes, long-standing diabetes, diabetes with retinopathy, neuropathy, or nephropathy, and in obese diabetics. The incidence in control subjects was not strikingly higher in those with a family history of diabetes (three in thirty-nine) or in acromegaly (one in eleven) than in other control subjects (three in fifty-one). Electron microscopic observations suggest that the lesion may be due to deposition of material in the collagen containing cuff of the capillary wall rather than to basement membrane thickening.
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.
Effect of Sulfonylurea Drugs on Plasma Free Fatty Acid and Blood Glucose Concentrations in Man
Authors: Stone Daniel B , Brown Joseph D
Published: December 2014

We have studied the effect of sulfonylurea drugs on plasma free fatty acid and blood glucose concentrations in man. The concentrations of plasma free fatty acids and blood glucose were measured after the oral administration of a single dose of sulfonylurea drugs to fasting, maturity-onset, ketoacidosis-resistant diabetic patients. The changes in concentration of glucose and free fatty acids were not parallel as they are after systemic insulin or intravenous tolbutamide. There was no significant decrease in glucose concentration during the first hour after oral administration and little decrease at the second hour, but then a decrease to a minimum at five to six hours. During the first two hours, however, the concentration of free fatty acids decreased significantly despite little change in glucose concentration. At two hours, the concentration of free fatty acids decreased to its minimum, despite the fact that glucose concentration continued to decrease until five or six hours. These results are consistent with our earlier in vitro data and with the interpretation that the sulfonylurea drugs may have a direct antilipolytic effect.
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.
Retinopathy, Nephropathy and Neuropathy in Lipoatrophic Diabetes: Case Report and Discussion
Authors: Marcus Robert , Alto Palo
Published: December 2014

The eighteenth patient with lipoatrophic diabetes has been reported. In addition to demonstrating all the criteria of this rare syndrome, he is the first on record who exhibits a broad variety of the complications of chronic diabetes mellitus. The significance of this fact is discussed.
Presence of Synalbumin Antagonist in Siblings of Diabetic Children
Authors: Ehrlich Robert M , Martin Julio M
Published: December 2014

Synalbumin antagonist was investigated in a group of forty-eight siblings of diabetic children. Nine parents of these patients, ten normal controls and eleven diabetic children were included in this study. In twenty-six of the forty-eight siblings synalbumin was detected. Glucose uptake by the rat hemidiaphragm was depressed from a mean of 13.36 to 0.99 mg. per cent of glucose per 10 mg. of tissue in ninety minutes incubation in the presence of 1,000 μU. of insulin. In five of nine parents tested, synalbumin was present. In only three of fourteen families in which two or more siblings were studied was synalbumin absent. These findings suggest a familial distribution of the antagonist. Fasting blood sugar, glucose tolerance test and plasma insulin were normal in synalbumin positive siblings. Negligible amounts of immunoreactive insulin were detected in the albumin extracted from nondiabetic relatives. The synalbumin did not interfere with the immunoassay of insulin. In extracts of insulin treated diabetics, various amounts of insulin were found. Five of eleven diabetics showed antagonism, three were border line, and three did not show antagonism. The results obtained suggest that synalbumin may be used as a genetic marker and encourage further investigation to assess the role of this inhibitor in the development of diabetes and as an indicator of prediabetes.
Postnatal Neogenesis of Islets of Langerhans in the Mouse
Authors: Bunnag Srichitra C
Published: December 2014

The source of the new islets during growth and the effect of aging on the number of islets have been studied in Webster Swiss mice. A combination of methods was employed, including microscopy in vivo, enumeration of the total number of islets, radioautography with H-3-thymidine, and conventional histological technics. The total number of islets in normal mice increases with age until about six months, and then becomes stable or decreases slightly. Radioautographs showed that the cells of the islets are in all likelihood derived from migrating ductal or periductal cells residing at the junction between the islet and pancreatic duct and at the periphery of the islet, and that these cells doubtless serve as the progenitor pool for the growth of the islet. The nuclear cycle of the insular cells was also determined by this method. In vivo study revealed that the structural integrity of ducts and of their vascular supply is important for the maintenance of the population of ductal and periductal islets.
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.
Effect of Diabetic Control on Retinopathy
Authors: Colwell John A
Published: December 2014

This paper presents an analysis of the literature regarding the effect of control of diabetes on retinopathy. In diabetics with age of onset before forty years of age and with a duration greater than fifteen years, there is a significantly higher incidence of retinopathy in those judged to have been under poor control than in those with better control. Those patients with poor control had a significantly higher incidence of the more severe forms of diabetic retinopathy. While this association does not necessarily imply a cause and effect relationship, it is not compatible with a point of view which accepts poor control as of little consequence in diabetes.
Early and Intensive Potassium Replacement in Diabetic Acidosis
Authors: Seftel H C , Kew M C
Published: December 2014

A patient with diabetic acidosis is described who nearly died from potassium deficiency developing ninety minutes after starting therapy with insulin. The patient received 715 mEq. of potassium chloride intravenously during the first twenty-four hours of treatment, 364 mEq. being given in the first nine hours to maintain life. Attention is drawn to the limitations of current recommendations regarding potassium repletion in diabetic acidosis.
Oral Glucose Tolerance Test in Normal Children
Authors: Pickens James M , Burkeholder James N , Womack William N
Published: December 2014

Glucose tolerance tests were performed on 200 healthy children, ranging in age from one to thirteen years, without a family history of diabetes. Those children past the age of six had higher blood sugar values at all points in the test, but significant differences were found only at fasting and at one-half hour. Sex and body build did not seem to influence the results. Fifteen per cent of the tests were “flat” with all values below 110 mg. per 100 ml. The use of these norms to interpret oral glucose tolerance tests in higher risk groups for diabetes mellitus is described.
Serum Insulin in Type I Glycogenosis: Effect of Galactose or Fructose Administration
Authors: Hug George , Schubert William K
Published: December 2014

Upon infusion of galactose, two patients with glucose-6-phosphatase deficiency did not respond with a rise in serum insulin while glucose elicited such a response. Similarly, infusion of fructose was followed by an increase in serum insulin, although no glucose was produced because of the glucose-6-phosphatase deficiency. Since fructose administered to patients with fructose intolerance does not have such an insulin releasing effect, it is speculated that an intermediary metabolite rather than fructose itself triggers the secretion of insulin.
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.
Maternal Carbohydrate Disorder and Congenital Malformations
Authors: Navarrete Victoriano N , Torres Isabel H , Rivera Irene R , Shor Velvl P , Grácia Pedro M
Published: December 2014

In 152 consecutively observed mothers who had delivered malformed infants intheir last pregnancy, 10 per cent had abnormal standard glucose tolerance tests and 45 per cent abnormal triamcinolone glucose tolerance tests. These findings are in contrast to a 3.3 per cent prevalence of abnormal triamcinolone glucose tolerance tests in a controlled group selected for absence of findings suggesting diabetes. The observation suggests that a relation exists between carbohydrate disturbance and the delivery of malformed infants.
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.
Failure of Synalbumin to Exhibit Insulin Antagonism in Vivo
Authors: Davidson Mayer B , Goodner Charles J
Published: December 2014

An insulin antagonistic albumin (human fraction V) was infused over a three-hour period into lightly anesthetized rats in an unsuccessful attempt to demonstrate an in vivo effect of synalbumin. This albumin antagonist did not affect the plasma insulin concentration or the establishment of steady blood glucose levels in nonfasted normal rats or the disposal of exogenous glucose in fasted normal rats. Synalbumin also had no effect on steady-state blood sugar or the handling of exogenous glucose in animals with limited insulin reserve (partially pancreatectomized). The hypoglycemic response to exogenous insulin was not altered. In vitro experiments showed that insulin insensitivity was not induced in the diaphragms of infused rats, nor did their plasma inhibit the action of insulin on normal diaphragms. It was concluded that on the basis of available evidence synalbumin could not be classed as a physiologically active substance.
Effects of Thyroid Function upon Insulin Secretion
Authors: Malaisse Willy J , Malaisse-Lagae Francine , McCraw Edward F
Published: December 2014

Insulin secretion provoked by glucose in the pancreas of the rat is not modified by addition of thyroxine to the incubation media. Secretion of insulin is reduced (by 34 per cent) by prior thyroidectomy and restored to normal after administration of thyroxine (15 μg./kg. body weight) in vivo to thyroidectomized rats. These changes occur despite normal insulin content of the pancreatic tissue. Treatment of normal rats by higher doses of thyroxine (2,000 μg./kg.) causes marked reduction (ca 40 per cent) of both pancreatic insulin content and secretion. These alterations suggest that thyroid hormones may exert a delicately balanced influence upon islet function in a chronic process.
Antagonism to Insulin Action on the Perfused Hind Limb of the Rat by a Reduced Insulin B Chain-Albumin Complex
Authors: Mahler Richard J , Szabo Olga , Penhos Juan C
Published: December 2014

A muscle perfusion technic, employing the hind limb of the rat, has been developed. Significant enhancement of glucose utilization by this tissue is seen with 500 μU./ml. of insulin. Maximal glucose uptake is seen at an insulin concentration of 1,000 μU./ml., although a significantly earlier insulin effect is noted when 10,000 μU./ml. is used.

The presence of 7.5 μg./ml. of a reduced B chain-albumin complex in the perfusion system causes highly significant inhibition of action of 1,000 μU./ml. of insulin. Neither equivalent concentrations of sulfonated B chain nor equimolar concentrations of a sulfhydryl donor, 2-mercaptoethanol, are capable of causing comparable insulin antagonism.
Passage of Insulin and Inulin Across Vascular Membranes in the Dog
Authors: Rasio E A , Mack E , Egdahl R H , Herrera M G
Published: December 2014

The equilibration of IRI and NSILA between arterial plasma and lymph was studied at different sites in sixteen anesthetized dogs. Lymph was collected from the thoracic duct in one group, from the main hepatic lymph vessel in another, and from the leg lymphatic in a third group. No baseline gradients were observed between arterial serum and lymph IRI concentrations. Lymph/serum NSILA concentration ratios were 0.62 ± 0.29 for leg lymph, 0.66 ± 0.20 for thoracic duct lymph and 0.84 ± 0.63 for hepatic lymph. Two tests were carried out in each dog:

(1) IVGTT (0.5 gm./kg.) Evans Blue was injected concurrently in some cases. Net glucose disappearance rate and serum IRI and NSILA patterns were similar in the three groups. Serum IRI passed rapidly into hepatic and thoracic duct lymph reaching plateau levels of 40 and 35 μU. per ml. respectively within 15 min. Leg lymph glucose concentration increased immediately but IRI appearance was delayed: A plateau of 20 μU, per ml. was reached after 30 min. No significant passage of Evans Blue into paw lymph was observed. Glucose injection was followed by a significant decrease in serum NSILA. Hepatic and thoracic duct lymph NSILA levels decreased slightly but NSILA concentration remained unchanged in leg lymph.

(2) One hour after the first test 0.2 U. per kg. of pork insulin and 25 uc 14C-inulin were injected intravenously. The patterns of distribution of these two substances were similar. Both reached peak concentrations first in hepatic lymph then in thoracic duct lymph. In paw lymph their appearance was delayed and the maximum concentration achieved was lower. It is concluded that differences in capillary permeability are likely to determine in part the distribution of IRI and NSILA in body fluids and thus may influence their biological activity.
Effect of Porcine Proinsulin in Vitro on Adipose Tissue and Diaphragm of the Normal Rat
Authors: Shaw Walter N , Chance Ronald E
Published: December 2014

The effect in vitro of porcine proinsulin and single component porcine insulin on the epididymal adipose tissue and the isolated diaphragm of the normal rat has been investigated. Both proteins enhance the oxidation of labeled glucose to carbon dioxide and its conversion to fatty acids by adipose tissue as well as glycogen formation from glucose by the hemidiaphragm. Kunitz pancreatic trypsin inhibitor (KPTI) but not the purified Kazal or soybean trypsin inhibitor block these effects of proinsulin on adipose tissue and diaphragm. KPTI has no effect on the response of these tissues to the single component insulin. Anti-insulin serum blocks the response of both adipose tissue and hemidiaphragm to proinsulin and single component insulin. The enhancement of the oxidation of carbon one of glucose to carbon dioxide by adipose tissue in the presence of proinsulin is also blocked by KPTI.

It is concluded that porcine proinsulin itself cannot affect the glucose metabolism of adipose tissue and hemidiaphragm of the normal rat. Proinsulin exerts the biologic effect seen in this study because it is converted by an enzyme or group of enzymes present in adipose tissue and diaphragm muscle, to a molecule which is similar to or identical with insulin.
Effect of Acute Elevation of Plasma Glycerol, Triglyceride and FFA Levels on Glucose Utilization and Plasma Insulin
Authors: Pelkonen Risto , Miettinen Tatu A , Taskinen Marja-Riitta , Nikkilä Esko A
Published: December 2014

The effects of raised plasma levels of glycerol, free fatty acids (FFA) and triglyceride on the disappearance rate (Kg) of intravenously administered glucose (25 gm.) and on the response of plasma immunoreactive insulin (IRI) to intravenous glucose were studied in thirty-six subjects. Increase of plasma glycerol level by oral glycerol augmented the Kg but not the glucose-stimulated plasma insulin level. Alimentary hyperglyceridemia enhanced the disappearance rate of glucose and the response of plasma insulin to glucose. Heparin injected intravenously during alimentary glyceridemia caused a five-to seven-fold increment of the levels of plasma FFA and glycerol but did not influence either the disappearance rate of glucose or the response of plasma insulin to glucose. Heparin injected in fasting state slowed significantly the disappearance rate of glucose, but did not change the insulin response.
Remarkable Sensitivity to Insulin in a Patient with Hypopituitarism and Diabetic Acidosis
Authors: DiRaimondo Vincent C , Earll Jerry M
Published: December 2014

A patient is described with panhypopituitarism and maturity-onset diabetes, complicated by diabetic acidosis. He exhibited a remarkable sensitivity to insulin, controlling his diabetes with an average of two units of insulin daily. He maintained increased sensitivity to insulin while in severe ketoacidosis and required only eight units of insulin to completely reverse this. Ketoacidosis does not directly result in insulin resistance, and it is possible that pituitary factors are essential. This case documents the importance of small basal levels of insulin in preventing ketoacidosis and lends further support to the concept that small levels of insulin serve as a “brake” on lipid mobilization. A delayed and prolonged response to insulin was observed in the panhypopituitary state.
Effect of Glucose Concentration on Insulin and Glucagon Release from Isolated Islets of Langerhans of the Rat
Authors: Vance James E , Buchanan Keith D , Challoner David R , Williams Robert H , Hickernell Barbara
Published: December 2014

The isolated islets of Langerhans of the rat have been utilized to study simultaneous insulin and glucagon release. There is very little degradation of insulin or glucagon when a proteolytic enzyme inhibitor, Trasylol, is added to the incubation vessels. Glucose exerts an opposite effect on insulin and glucagon release. As the glucose concentration in the incubation media is raised from 30 to 300 mg. per 100 ml., there is a decreased secretion of glucagon and an increased secretion of insulin. The addition of 2-deoxyglucose to the media inhibited insulin release but had no effect on glucagon. The results are discussed in reference to the role of glucagon in insulinogenesis and in regard to the possible mechanisms of insulin and glucagon release.
Studies of the Metabolism of Isolated Livers of Normal and Alloxan-diabetic Rats Perfused with Insulin
Authors: Haft David E
Published: December 2014

Livers of fed normal and diabetic rats were perfused in the presence of glucose-l-C-14 and acetate-H-3 in order to study their metabolism with and without addition of insulin to the medium. Glucose was added to bring the initial medium level to 436 ± 6 mg./100 ml. Net glucose removal occurred only with normal rat livers. Livers of diabetic rats showed progressive impairment of glucose uptake and increase in glucose production as the interval from the last maintenance insulin injection was prolonged. Whereas these chronically diabetic animals had livers with low glycogen content, decreased lipogenesis, and increased uro genesis, rats which had received 1.5 U. protamine insulin on the previous day were fully hyperglycemic but yielded livers showing normal fatty acid and urea synthesis along with excessively high glycogen. Insulin addition lowered perfusate amino nitrogen levels with normal and diabetic livers but did not significantly affect glycemia in any series and had only small stimulatory effects on lipogenesis and glucose oxidation in livers of rats three to five days off insulin. The data suggest that although insulin has important direct effects on liver metabolism, its hepatic action does not explain its early in vivo hypoglycemic effect in diabetes.
Plasma Glucose, Free Fatty Acids, and Immunoreactive Insulin in Sixty-six Obese Children: Studies in Reference to a Family History of Diabetes Mellitus
Authors: Paulsen Elsa P , Richenderfer Lee , Ginsberg-Fellner Fredda
Published: December 2014

Oral glucose tolerance tests (1.75 gm./kg. ideal body weight) were performed on sixty-six obese children and adolescents, four to sixteen years of age. Ten subjects of normal height and weight of the same age range and without a family history of diabetes served as controls. Plasma glucose, immunoreactive insulin, and free fatty acid levels were determined.

Twenty-seven (45 per cent) of the subjects had normal tolerance, fifteen (23 per cent) had distinctly abnormal tolerance. Hyperinsulinemia was observed in nearly all the obese subjects, but it was significantly greater in those with abnormal tolerance than in those with normal tolerance. Free fatty acids fell rapidly after the ingestion of glucose in the majority of subjects. In some there was a delay in return to fasting levels.

Thirty-four of the obese subjects had close diabetic relatives (diabetic family history [DHF+]) and thirty-two did not (DFH −). The incidence of moderately abnormal tolerance in the two groups, was the same but markedly abnormal tolerance was found only in the DFH + group. DFH + children had significantly greater elevations in insulin levels than DFH − children at both levels of tolerance. The DFH + subjects with severe hyperglycemia had somewhat increased levels of insulin occurring only after the first hour of the test.

The hyperinsulinemia observed in the obese children in this study cannot be completely explained by compensatory overproduction due to peripheral resistance to insulin, and an alternate hypothesis is suggested.
The Short-term Prognosis in Diabetic Neuropathy
Authors: Mayne N
Published: December 2014

Seventy-three patients with diabetic neuropathy have been followed for periods ranging from two to four and three-quarter years. Symptoms of neuropathy tended to improve though some patients thought that numbness became more severe. Of the signs of neuropathy, weakness and hyperalgesia or hyperesthesia usually improved, impaired pain sensation deteriorated twice as often as it improved, and ankle jerks, vibration sense at the ankles, and position sense in the big toes usually remained the same. Impairment of these last three signs occurred as frequently in a random group of diabetic patients as in the present selected series and was therefore not a feature of symptomatic neuropathy.
Metabolic Effects of Nicotinic Acid in Acute Insulin Deficiency in the Rat
Authors: Gross Richard C , Carlson Lars A
Published: December 2014

To investigate the role of increased free fatty acid (FFA) mobilization in the hyperglycemia, ketonemia, hyperlipemia and fatty liver produced by acute insulin deficiency, nicotinic acid was used to inhibit FFA mobilization in rats given guinea pig anti-insulin serum (AIS). Effects on concentration of plasma FFA, blood glucose and betahydroxybutyric acid (BHBA), and plasma and liver lipids were studied acutely after nicotinic acid administration and during six and twenty-four hours of treatment with this compound.

Nicotinic acid produced an immediate fall in plasma FFA and a lesser but significant decrease in blood glucose when given two hours after AIS. When treatment was begun simultaneously with administration of AIS and repeated every four hours, plasma FFA and plasma and liver lipids were kept at normal control levels or lower for at least six hours, and blood BHBA for eighteen hours. Blood glucose remained at 70 per cent of values in untreated rats for eighteen hours, yet exceeded control levels during this time. At twenty-four hours there were no important differences between treated and untreated animals in any parameter except plasma triglycerides. This change was possibly related to a rebound of FFA levels in the nicotinic acid treated group.

The effects of nicotinic acid on plasma FFA, blood BHBA and plasma and liver lipids are most likely due to inhibition of FFA release from adipose tissue. Increased FFA mobilization in acute insulin deficiency could thus explain the increase in concentration of these substances during the first several hours after AIS administration. The mechanism of action of nicotinic acid and the influence of plasma FFA levels on glucose concentration is less clear.
Effects of Plasma Albumin on Glycolytic Intermediates in Rat Diaphragm Muscle
Authors: Karl Irene E , Voyles Nancy , Recant Lillian
Published: December 2014

The effects of a variety of albumin fractions and subfractions (human and bovine) on the steady state levels of the glycolytic intermediates and cofactors of muscle and adipose tissue were tested in vitro. In muscle, the pattern is characterized by decreases in pyruvate (Pyr), adenosinetriphosphate (ATP) and phosphocreatine (PC) and increases in phosphoenolpyruvate (PEP), 3 phosphoglycerate (3PG), αglycerophosphate (αGOP) and dihydroxacetonephosphate (DHAP). There are no marked changes in glycogen (Gly), glucose-6-phosphate (G6P), fructose-diphosphate (FDP), lactate (Lac), adenosine-mono- and diphosphates (AMP, ADP), and inorganic phosphate (Pi). The Lac to Pyr ratio is increased while the αGOP to DHAP ratio is unchanged. There appears to be no change in pyridine nucleotides in the presence of albumin.

Although all preparations tested were active in producing these substrate changes, the albumin molecule per se is probably not the active factor since albumin, from which a small molecular component designated as X is removed, has lost its capacity to alter the substrates of the glycolytic pathway as well as its insulin inhibitory activity.

The nature of the substrate changes in the presence of albumin suggests either a block of the pyruvate kinase enzyme with subsequent accumulation of glycolytic intermediates behind the block or an enhancement of conversion of Pyr to PEP. Studies with Pyr indicate the capacity of muscle to convert Pyr to PEP, but they do not elucidate the nature of the albumin-induced substrate changes.The addition of insulin or anti-insulin serum in vitro does not reverse these changes.

In rat adipose tissue the presence of albumin does not inhibit insulin action nor does it appear to produce the above substrate changes.

The pathophysiologic significance of these observations remains to be demonstrated.