bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Insulin on Excretion of Nitrogen in Normal, Depancreatized, and Steroid-Diabetic Rats
Authors: Ingle Dwight J
Published: December 2014

Sexually mature male rats in metabolism cages were adapted to the tube-feeding of a medium carbohydrate diet. In experiment 1, intact rats were fasted for 96 hrs. Injection of glucagon-free insulin caused an increase in urinary NPN. Cortisone caused a greater loss of NPN which was not significantly changed by addition of insulin. In experiment 2, intact tube-fed rats excreted amounts of NPN and glucose increased in proportion to the dose of cortisone. Glycosuria but not nitrogen loss was suppressed by insulin. In experiment 3, the spontaneous glycosuria of partially depancreatized rats was suppressed by insulin and the elevated urinary NPN was also suppressed. When the glycosuria of partially depancreatized rats was induced or aggravated by cortisone it could be suppressed by insulin but the level of urinary NPN remained high.
Measurements of the Enzymatic Activities Required for ATP Formation by Glycolysis in the Pancreatic Islets of Hyperglycemic Mice (NZO)
Authors: Brolin S E , Berne C , Linde B
Published: December 2014

Metabolic studies with 1-C-14 and 6-C-14 glucose have led to the assumption that the glycolytic degradation of glucose is of minor importance in the islets. In the present investigation the enzymatic activities of phosphoglyceric kinase and pyruvic kinase are measured in the pancreatic islets and acini, since these enzymes are required for the glycolytic formation of ATP. The activities are obviously high and significantly highest in the islets. The enzymes linked to the conversion between NAD and NADH show much lower activities. In accordance with the general conception of the pacemakers in the anaerobic breakdown of glucose, glyceraldehyde-3-phosphate dehydrogenase may be assumed io be rate limiting for the glycolytic formation of ATP. This possibility is discussed with reference to the low activity of phosphofructokinase found in the islets.
Specificity of the Effect of Insulin on Permeability of Frog Sartorius Muscles to Sugar
Authors: Wohltmann Hulda J , Narahara H T , Wesley M E
Published: December 2014

The permeability of isolated frog sartorius muscles to 3-O-methylglucose is increased by low concentrations of insulin, but is relatively insensitive to a variety of other peptides and proteins, many of which have been reported to enhance the uptake and metabolism of glucose by rat hemidiaphragms or adipose tissue in vitro. ACTH, growth hormone, oxytocin, vasopressin and the separated chains of oxidized insulin and of insulin S-sulfonate did not alter the permeability of frog muscles to sugar when tested either alone or together with a submaximal concentration of insulin. These substances were able to retard the degradation of I-131 insulin by frog muscle extracts, but, in contrast to the situation for rat hemidiaphragms, media that had been used for incubation of frog sartorius muscles exhibited only a barely detectable ability to degrade I-131 insulin. The results suggest that some of these peptides may augment the effect of insulin on rat hemidiaphragms by diminishing the rate of degradation of insulin in the medium. Glucagon increased the permeability of frog muscles to sugar, but this effect seemed to be attributable to contamination of the preparation with insulin. Prolactin, TSH and epinephrine augmented permeability to 3-methylglucose when used at concentrations that were higher than those ordinarily found in plasma.
Studies of Human Insulin from Nondiabetic and Diabetic Pancreas
Authors: Kimmel Joe R , Pollock H G
Published: December 2014

Insulin has been isolated from single human pancreases from diabetic and nondiabetic sources. Purification was accomplished primarily by gel filtration. The average yield of insulin from the nondiabetic pancreas was 8.6 mg. per 100 gm. of tissue, and from the diabetic pancreas 2.9 mg. per 100 gm. The amino acid composition of nondiabetic insulin was in agreement with the known structure of human insulin. The insulin isolated from the diabetic pancreas had the same amino acid composition as normal human insulin in all cases but one. Based upon the amino acid analysis, it is possible that a different amino acid sequence occurs in the insulin from this diabetic source.
Influence of Insulin on Liver Vitamin A in Rats
Authors: Bowles W H
Published: December 2014

Both Regular and globin-type insulins interfered with storage of vitamin A in the livers of rats by all routes of injection. Regular insulin, injected subcutaneously, had the least effect. Injected insulin increased the rate of depletion of previously stored vitamin A from the liver. Alloxan diabetes had no effect upon liver storage of ingested vitamin A nor upon the rate of depletion of vitamin A from the liver.
Lipoatrophic Diabetes and Mental Illness in Three Siblings
Authors: Jolliff James W , Craig James W
Published: December 2014

Three siblings with the syndrome of lipoatrophic diabetes who developed paranoid psychoses are described. Their parents and the other five siblings in the family were also studied. None of the other five siblings has been psychotic and none of them has diabetes mellitus or lipoatrophy. Although there is a family history of both diabetes mellitus and psychosis, a history of lipoatrophy was not obtained. There are several published descriptions of the occurrence of psychiatric disorders in patients with lipodystrophy. The findings in these siblings and in reports in the medical literature suggest that lipodystrophy may predispose, in some yet undefined manner, to the development of mental illness.
Metabolism, Blood Levels and Rate of Excretion of Acetohexamide in Human Subjects
Authors: Galloway J A , McMahon R E , Culp H W , Marshall F J , Young E C
Published: December 2014

The metabolism of acetohexamide was studied in normal and diabetic subjects,utilizing acetohexamide-C-14 and hydroxyhexamide-C-14 in two types of experiments. In one, blood levels were determined by an isotopic dilution analysis (IDA). In the other, following the oral and intravenous administration of acetohexamide-C-14, radiocarbon levels in the blood and urine and the nature of the urinary metabolites were elucidated. IDA showed an average half-life for acetohexamide of 1.6 hrs. (range 0.8 to 2.4) and an average half-time for its principal metabolic product, hydroxyhexamide, of 5.3 hrs. (range 3.7 to 6.4). Half-time for total radiocarbon was 5.3 hrs. (range 3.5 to 11). Urinary recovery ofradioactivity after oral doses averaged 71.6 per cent in twenty-four hours.

Of the urinary metabolites of acetohexamide (AH) recovered, about 65 per cent was L-hydroxyhexamide (HH) and the remainder consisted chiefly of 4-trans-hydroxyacetohexamide (HAH), 4-trans-hydroxyhydroxyhexamide (HHH), and unchanged acetohexamide with small quantities of other hydroxylated isomers. Fecal excretion was measured in one patient followingthe oral administration and found to be 15 per cent. The observation that, even followingintravenous injection, urinary recovery was only 85 per cent suggested that biliary excretion represents the secondary route of elimination of acetohexamide and/or its metabolites. The radioactivity which was not recovered in the urine at the end of 48 hrs., e.g., on the average 25 per cent, was probably excreted in the stools, resulting from the failure of a small quantity of the tablet to be absorbed and from biliary excretion. The blood and urine data agree with those reported by Sheldon, Anderson and Stoner and confirm the report by Smith, Vecchio and Forist that the half-life of acetohexamide (AH) plus hydroxyhexamide (HH) is comparable to that of tolbutamide. In spite of this relatively short half-life, limited blood sugar data indicate definite hypoglycemic effects up to 24 hrs. after a single 1.0-gm. dose. These findings indicate that the duration of action of AH and its metabolites are not necessarily related to drug levels.
Critical Analysis of Blood Sugar Measurements in Diabetes Detection and Diagnosis
Authors: Whichelow M J , Wigglesworth A , Cox B D , Butterfield W J H , Abrams M E
Published: December 2014

An analysis of 702 blood sugar levels during glucose tolerancetests shows that the site of blood sampling influences the blood sugar result. Capillary blood taken from the warm ear lobe gives an accurate reflection of the arterial blood sugar level. Compared to the arterial level the venous blood sugar level is unpredictable and differs from the arterial to a varying extent, e.g., from +26 mg. per 100 ml. to −4 mg. per 100 ml. at two hours in the glucose tolerance test depending on many factors.

Studies of the macromethod in the AutoAnalyzer indicate that although the reproducibility is good, the volume of blood pumped by the proportioning pump is inaccurate (too small). Analysis of the micromethod shows that the reproducibility is also good, though not quite so good as the macromethod. However, the sample volume taken for analysis by the proportioning pump is accurate.

Reasons are given for recommending that capillary, not venous, blood be taken, and that the ferricyanide-reducing micromethod on the AutoAnalyzer be used for blood glucose estimation.
Effects of Co-ingestion of Fat and Protein Upon Carbohydrate-Induced Hyperglycemia
Authors: Estrich David , Ravnik Anthony , Schlierf Guenter , Fukayama George , Kinsell Laurance
Published: December 2014

The effects of test “loads” containing 50 gm. glucose (CHO); 50 gm. glucose + 30 gm. protein + 40 gm. fat (CHO + P + F) ; 50 gm. glucose + 30 gm. protein (CHO + P); 50 gm. glucose + 40 gm. fat (CHO + F) on plasma glucose, FFA, insulin, and alpha amino nitrogen have been evaluated in adult-onset diabetics. In comparison with CHO, CHO + P + F results in much lesser elevation of plasma glucose. The effect of CHO + P + F is greater than the sum of the effects of CHO+P and CHO+F. Apparently the CHO+P+F pattern is attributable to relatively or absolutely increased insulin release plus modified glucose and protein absorption.

On the basis of theoretical and clinical observations, there appears to be good reason to consider the use of diets containing considerable amounts of protein and fat in adult- and juvenile-onset diabetics.
Studies of Insulin Antagonism: I. An Artifactual Antagonist to Insulin and Plasma Nonsuppressible Insulin-like Activity Occurring in Preparation of “Albumin”
Authors: Ensinck John W , Poffenbarger Phillip L , Hogan Richard A , Williams Robert H
Published: December 2014

Because ILA was encountered in TCA-ethanol extracts of plasma dialyzed in boiled Visking casing which interfered with measurement of the “synalbumin insulin antagonist” on isolated muscle, a systematic study of the influence of the casing on these factors was undertaken. Plasma from healthy humans was extracted with TCA-ethanol and dialyzed in nonboiled and boiled Visking casing. The extract (“albumin”) was tested by measurement of glucose uptake in rat hemidiaphragms, without and with insulin (1,000 βU./ml.). Significant amounts of both ILA and anti-insulin activity weredetected in both “albumins” at 3 to 5 gm. per cent; however, more ILA and less insulin inhibition was found in “albumin” dialyzed in boiled casing. The magnitude of ILA could not be accounted for by immunoreactive insulin levels in the “albumin,” and the ILA was not suppressed by insulin-specific antiserum (NSILA).

From dose-response curves measuring glucose uptake and glycogen synthesis, more NSILAwas detected in the “albumin” from boiled casing; however, at 3 to 5 gm. per cent concentration, “albumin” dialyzed in either casing caused inhibition of NSILA. Because partially purified NSILA was found to be retained equally by either boiledor nonboiled casing, an antagonist in Yisking casing was sought. A substance from Viskingcasing with small molecular weight was found to cause insulin inhibition. When nonantagonistic crystalline albumin was dialyzed in nonboiled casing, marked antagonism to both crystalline insulin and partially purified NSILA was demonstrated.

It is concluded that an artifactual casing antagonist to both NSILA and insulin is bound to albumin and may contribute to the measurement of the “synalbumin insulin antagonist.”
Mechanism of Action of Phenethylbiguanide in Normal Subjects
Authors: Pereira Virgilio Goncalves , Wajchenberg Bernardo Léo , Shnaider José
Published: December 2014

Administration of phenethylbiguanide (DBI) to fifteen normal adult controls in a single dose of 200 mg. had no effect on fasting blood sugar. DBI increased the tolerance to glucose and insulin responsivity, provided that glucose was given simultaneously in the latter test. It is suggested that the hypoglycemic action of DBI in healthy peopleis only evident when adequate substrate (glucose) is available in the presence of insulin to “push” glucose entry into the cell. That it is not simple potentiation ofinsulin action is suggested by a smaller decline in free fatty acids (FFA) during intravenous glucose infusion despite a greater increase in glucose.
The Incipient Asymptomatic Diabetic Bladder
Authors: Ellenberg Max , Weber Herbert
Published: December 2014

To explore the problem of initial manifestations of the diabetic neurogenic bladder, diabetic patients with and without neuropathy and nondiabetic controls, all without symptoms or signs referable to the urinary tract, were studied urologically. The nondiabetic controls and the diabetics without neuropathy were normal. In striking contrast, 83 per cent of diabetic patients with neuropathy had clear, objective evidences of neurogenic bladder involvement as manifested by abnormal cystometrograms, and grossly enlarged bladders. However, the absence of residual urine was the rule. The typical case had no pyuria or bacteriuria, a negative bladder urine culture, no azotemia, pyelonephritis, sepsis or significant albuminuria.

This differs sharply from the advanced diabetic neurogenic bladder with paralysis where there is a marked residual urine with secondary infection, pyuria, bacteriuria, positive urine cultures, pyelonephritis, sepsis, azotemia and conspicuous albuminuria. The disparity is determined by the factor of residual urine which is the measure of decompensation.

It is suggested that the progressive decompensation of the incipient asymptomatic diabetic bladder is a cause of the increased frequency of renal infection in the diabetic.
Impairment of Carbohydrate Metabolism of the Squirrel Monkey
Authors: Davidson J W F , Lang C M , Blackwell W L
Published: December 2014

Studies on over fifty squirrel monkeys have revealed the prevalence of an imbalance of carbohydrate metabolism. Nearly half of the colony of adult female monkeys were found to exhibit both abnormal glucose tolerance and diagnostic tolbutamide curves when maintained on a standard commercial diet and under satisfactory laboratory conditions. The impaired monkeys commonly demonstrated normal fasting blood sugar levels and were without overt symptoms of diabetes, although occasionally frank symptoms of hyperglycemia and glucosuria were found in the colony. Several impaired animals responded to treatment with oral tolbutamide with apparent restoration of normal carbohydrate metabolism, but tolbutamide treatment did not improve the glucose tolerance of others. Although prevalence of atherosclerosis exists also in adult squirrel monkeys, no correlation of serum cholesterol and nonesterified fatty acids was found between normal monkeys and animals with carbohydrate impairment.
Insulin-like Activity
Authors: Batchelor Bruce Robert
Published: December 2014

This presentat ion is a review of the ILA concept and considers (1) major insulin assays; description, comparison, and variation of results; (2) location of circulating ILA in the plasma proteins by various technics; (3) types of ILA: “free-bound,” “typical-atypical,” “suppressiblenonsuppressible,” “NSILA,” and other forms; (4) inhibitory or antagonistic factors: synalbumin-antagonistic albumin and nonesterified fatty acids; and (5) the ILA concept with respect to vascular membranes and the glucose transport theory. Also included are data comparing insulin levels obtained by the major assays, types of ILA-insulin levels and properties of the various forms of insulin.
Effects of Hyper- and Hypoglycemia on Beta Cell Degranulation and Glycogen Infiltration in Normal, Subdiabetic and Diabetic Rats
Authors: Carpenter A -M , Lazarow A
Published: December 2014

With the use of linear scan technics, on aldehyde-fuchsin stained slides, islet volume and beta cell volumes were quantitated in pancreas of diabetic, subdiabetic and normal rats. Glycogen infiltration was assessed on PAS-stained slides. Subdiabetic and normal animals had been injected intraperitoneally with 40 per cent glucose (4.0 gm./ kg.) at hourly intervals for two and four hours; controls were injected with saline.

Progressive degranulation of beta cells was observed as the period of glucose injection was prolonged. Glycogen infiltration was inversely related to degranulation of beta cells; the cytologic results were related to blood sugar values obtained at hourly intervals.
Studies of Substrate Regulation in Fasting: I. Evidence for Central Regulation of Lipolysis by Plasma Glucose Mediated by the Sympathetic Nervous System
Authors: Goodner Charles J , Tustison Winston A , Davidson Mayer B , Chu Ping-Chi , Conway Martin J
Published: December 2014

Infusion of glucose into fasting normal subjects at rates of 20 to 100 mg. per minute caused a transient fall in arterial plasma free fatty acids. The arterial glucose was raised only 3 to 10 mg. per 100 ml. by these infusions and plasma immunoreactive insulin did not change. During the recovery phase after an initial response to glucose FFA were refractory to a second challenge with glucose. Fructose was less potent than glucose in inducing a fall in FFA. Similar responses to glucose could be obtained in insulin-dependent diabetics after priming with long-acting insulin providing further evidence that the response of lipolysis to glucose does not require an acute change in insulin. Infusion of glucose intra-arterially failed to affect the local release of FFA. Beta-adrenergic blockade and ganglionic blockade abolished the response of FFA to these doses of glucose. These data suggest but do not establish the hypothesis that sympathetic tone to adipose tissue is under continuous regulation by the central nervous system and that the concentration of arterial blood glucose is the signal for this substrate controlling system.
Juvenile Diabetes Mellitus, a Deficiency in Insulin
Authors: Parke Mary L , Pildes Rosita S , Chao Kuen-Lan , Cornblath Marvin , Kipnis David M
Published: December 2014

The plasma insulin, growth hormone, nonesterified fatty acids and glucose responses to the oral ingestion of glucose, the intravenous administration of tolbutamide and the infusion of arginine were studied in fourteen newly diagnosed juvenile diabetic children. Fasting plasma insulin levels did not differ significantly between diabetic and normal children, although the mean fasting blood glucose level of the diabetic children was threefold greater than that of the normal subjects No detectable plasma insulin response was observed in the diabetic subjects during all three tests. Fasting plasma growth hormone levels and plasma growth hormone responses were similar in both normal and diabetic children. The fasting free fatty acid level of the diabetic children was significantly higher than in normal children, but fell during all three tests. With use of a variety of sensitive procedures, no antibodies to human insulin were demonstrable in the sera of newly diagnosed juvenile diabetics.
Defective Plasma Insulin Response during Prednisolone Glucose Tolerance Tests in Subclinical Diabetic Mothers of Heavy Infants
Authors: Kalkhoff R K , Richardson B L , Stoddard F J
Published: December 2014

Plasma glucose and immunoreactive insulin (IRI) were measured during four-hour oral glucose tolerance tests (GTT) and prednisolone glucose tolerance tests (PGTT) in thirty-six women suspected of having diabetes mellitus because they had recently delivered an infant weighing nine pounds or more. The results were compared to similar tests performed on ten nonobese women who had given birth to normal weight infants. All diabetes suspects had normal GTT, and the total IRI response (area circumscribed by the plasma insulin response curve) was similar to the control group. During PGTT, seventeen of the thirty-six suspects had a mild diabetic curve (44 per cent) despite the finding that total plasma IRI response remained similar to the control individuals and the nineteen suspects who had normal PGTT. Examination of the pattern of the hormonal response, however, revealed that in the subclinical diabetic group plasma insulin levels at thirty minutes during PGTT were subnormal relative to abnormally high plasma glucose concentrations at this time interval. This defect was not observed during GTT, when all individuals had normal carbohydrate tolerance. The majority of women who delivered large infants were also moderately obese whether or not diabetes was present. The results of these studies indicate that most women with subclinical diabetes mellitus who deliver large infants will escape detection in the immediate postpartum period if the evaluation is limited to a standard oral GTT. The impaired glucose tolerance elicited during PGTT would appear to be directly related to a defective insulin response during the initial thirty to sixty minutes following oral glucose administration and is spontaneously reversible when a diabetogenic stress such as that produced with oral glucocorticoids and presumably pregnancy is not present.
Plasma Glucose Levels in Normal and Adrenalectomized Mice Treated with Streptozotocin and Nicotinamide
Authors: Schein Philip S , Bates Robert W
Published: December 2014

Serial alterations in blood glucose of normal and adrenalectomized mice following the administration of a diabetogenic dose of streptozotocin have been compared with those of similar mice pretreated with nicotinamide. An initial hyperglycemic phase, one to three hours post-injection, was observed with both streptozotocin and nicotinamide treated mice, and was drug related. In the case of streptozotocin the early elevation in blood sugar was not dependent on the presence of the adrenal gland. An initial hyperglycemic phase was recorded in fed adrenalectomized mice but was eliminated in fasted adrenalectomized mice because of decreased liver glycogen. A hypoglycemic phase at seven hours was observed with streptozotocin treatment. This was associated with a seven-fold increase in plasma immunoreactive insulin (IKI) concentration observed in streptozotocin treated normals. By twenty-four hours the streptozotocin treated mice were permanently diabetic, and had significantly depressed pancreatic insulin concentrations, while plasma insulin was still greater than control concentrations. The nicotinamide protected group demonstrated no evidence of diabetes. The mechanism of diabeto genesis of streptozotocin differs from that of alloxan.
Diabetic Retinopathy: A Further Study of Prognosis for Vision
Authors: Caird F I , Burditt Anne F , Draper G J
Published: December 2014

Prognosis for vision has been studied in 135 patients with diabetic retinopathy and good vision and compared with that in 228 diabetics without retinopathy similarly studied. The risk of “blindness” in diabetics with retinopathy whose diabetes was diagnosed under the age of sixty was 3 per cent in five years, and 20 per cent in those diagnosed over that age. The risk of “visual impairment” also increases with age at diagnosis.

Fifty per cent of a small group of diabetics with “malignant retinopathy” were “blind” in five years, and only 14 per cent preserved good vision.

One third of forty-six diabetics had good vision in one eye one year and four years after their first vitreous hemorrhage. One third had “impaired vision”, and one third were “blind”.
A Double Antibody Immunoassay for Glucagon
Authors: Hazzard William R , Crockford Peter M , Buchanan Keith D , Vance James E , Chen Robert , Williams Robert H
Published: December 2014

A double antibody adaptation of the glucagon radioimmunoassay is described in detail. Guinea pig antiserum allowing the assay of 2,500 unknowns per milliliter of undiluted serum was induced by biweekly immunization. Glucagon was iodinated with I-125 and purified by elution from a cellulose column, maximal immunoprecipitibility approximating 80 per cent. Standard curves in buffer were sensitive to purified glucagon in amounts of less than 100 μμg.

Rapid degradation of labeled glucagon added to human blood was demonstrated. Trasylol was confirmed as an effective inhibitor of this degradation. Endogenous plasma immunoreactive glucagon (IRG) appeared less labile and may have interfered with the quantitative detection of unlabeled exogenous beef-pork glucagon in plasma recovery studies.

The hypothesis is offered that plasma IRG, herein measured at 400 ± 220 (S.D.) μμg./ml., may be composed of a pancreatic and an extrapancreatic fraction of similar but not identical immunological activity. The cross-reactivity of the two components remains a problem in the interpretation of the glucagon immunoassay as applied to plasma.
Effects of Acute Experimental Pancreatitis on Insulin Metabolism in the Dog: Application of a New Equilibrium Infusion Technic
Authors: Pi-Sunyer Xavier , Byrne John J , Freinkel Norbert
Published: December 2014

Experimental pancreatitis has been induced in dogs by instillation of bile into the pancreatic duct. An equilibrium infusion technic with I-131-insulin has been employed to evaluate the subsequent changes in the plasma levels of immunoreactive insulin (IRI). Evidence for acute intravascular insulinolysis (due to a putative release of pancreatic proteases and/or peptidases into the circulation) could not be demonstrated. Changes compatible with modest, late attenuation in the rates of insulin degradation were observed in some studies. However, in all experiments, the induction of pancreatitis effected prompt increases in total plasma IRI which exceeded concurrent changes in the “steady-state” concentration of infused I-131-insulin. Thus, the elevations of plasma IRI were greater than could be ascribed to alterations in insulin degradation or distribution. Direct analysis of pancreatic venous effluent indicated that the “extra” IRI originated, at least in part, from a purge of preformed pancreatic insulin or immunologically reactive insulin-like material. It displayed the same immunological reactivity on serial dilution as IRI released in response to conventional hyperglycemia. Consideration of the concomitant changes in plasma glucose and FFA during acute pancreatitis suggested that insulin-like effects may be greater in the liver than the periphery.
Glucose Metabolism in Normal and Obese Subjects: Effect of Phenformin
Authors: Kreisberg Robert A
Published: December 2014

The purpose of the experiments described in this paper was to determine whether phenformin altered the metabolism of glucose in subjects in whom it did not lower the blood sugar. Glucose-1-C-14 was utilized to investigate the metabolism of glucose in eight normal and eight obese subjects before and after phenformin.

Phenformin increased the turnover, recycling and conversion of glucose to lactate and decreased the oxidation of glucose in all of the normal subjects studied. The increase in glucose turnover was due entirely to the increase in glucose recycling since net glucose turnover (glucose derived from all sources except the Cori cycle) did not change. Phenformin also increased glucose turnover and recycling in obese subjects but in contrast to normals, its effect.s on glucose oxidation and glucose conversion to lactate were more variable.

These results establish that phenformin has clearly defined effects on the metabolism of glucose in subjects in whom it exerts no hypoglycemic action and support the concept that phenformin increases glucose utilization by diverting it from oxidative to nonoxidative pathways in peripheral tissues.
Plasma Concentrations of A and B Chains of Insulin in Nondiabetic, Diabetic and High Risk Potential Diabetic Subjects
Authors: Varandani P T
Published: December 2014

Radioimmunoassays for the measurement of the A chain and B chain of insulin in the presence of insulin are described. The assays are sensitive to 0.3 ng./ml. each of A chain and B chain. The results of the immunoassays of human plasma indicate that both A and B chains are present in human plasma. The criteria for this evidence were (a) quantitative recovery of added A and B chains from plasma and (b) parallel relationships between the standard curves of A and B chains and results upon dilution of plasma. The mean concentrations of A chain and B chain in plasma from nondiabetic subjects were 3.7 ± 1.0 and 3.4 ± 1.1 ng./ml., respectively. The concentrations of A chain were markedly higher in diabetic and high risk potential diabetic subjects. It appears possible that an elevated level of A chain may be used as a diagnostic criterion for prediabetes. There was no apparent effect of oral glucose on the concentration of A and B chains in the plasma of nondiabetic subjects as that observed on the concentration of insulin.

Studies on the immunospecificity of the cysteine residues of the two chains showed that thiol, S-sulfonated, oxidized and S-carboxymethylated chains reacted similarly; this indicates that S-sulfonated cysteine residues are probably not involved in the antigen-binding reaction.
Synalbumin Insulin Antagonism in Idiopathic Hypoglycemia of Infancy
Authors: Sherman Lawrence , Rosenbloom Arlan L
Published: December 2014

Infantile idiopathic hypoglycemia appears to be an early manifestation of an early manifestation of an inherited metabolic defect that leads to diabetes mellitus. Eight children with this form of hypoglycemia were studied for the presence of synalbumir insulin antagonism. All had diabetes in one or both parenta families. Two of the children had normal antagonist level. before and after they developed chemical diabetes. A thirt child was tested twice after she was found to have chemica diabetes, and on each occasion had normal antagonist levels. Rather than a causa sine qua non for the develop ment of diabetes, or a constant feature of the disorder, ex cess synalbumin insulin antagonism appears to be a variable expression of a more fundamental metabolic abnormality ir essential diabetes mellitus.
Diabetes in the Cocopah Indians
Authors: Henry R E , Burch T A , Bennett P H , Miller Max
Published: December 2014

One hundred and eighty-two Cocopah Indians, aged five years and over and representing 81 per cent of the study population, were given a 75 gm. glucose equivalent load and determinations were made two hours later of plasma glucose levels. Seventeen per cent of the population at the time were either receiving hypoglycemic therapy or had plasma glucose levels of at least 160 mg. per 100 ml., which was considered indicative of “diabetes.” In those aged thirty-five years and over, the prevalence was 34 per cent, similar to that reported in the Cherokee but lower than that in the Pima Indians.

The frequency of obesity in those aged fifteen and over was higher in the Cocopah than in the Pima Indians but, as the prevalence of “diabetes” was lower in the Cocopah, the frequency of obesity did not appear to account for the difference in the prevalences of diabetes between these tribes.
Interrelationship of Vascular Disease and Blood Lipids in Young Indian Diabetics
Authors: Ahuja M M S , Kumar Vinod , Gossain V V , Garg V K
Published: December 2014

Clinical and laboratory data on 100 young diabetic patients in a North Indian urban population were obtained to determine the prevalence of vascular disease and its relation to certain clinical factors. The findings revealed evidence of vascular disease in 32 per cent of young diabetics as retinopathy (15.0 per cent), coronary artery disease (myocardial infarction and angina pectoris, 14 per cent) and nephropathy (10 per cent). Duration of disease, dietary habits, or the mode of treatment and control of diabetes did not appear to be related to the development of vascular disease. Total serum lipid content and triglycerides were elevated in those who manifested clinically objective vascular disease.
Zinc Glucagon Depression of Blood Amino Acids in Rabbits
Authors: Bromer William W , Chance Ronald E
Published: December 2014

Single doses of glucagon and zinc glucagon were administered to fed rabbits and changes in blood glucose and total blood amino acids were measured. The concentration of amino acids was depressed longer with zinc glucagon (about 30 per cent decrease for at least twelve hours) than with glucagom. A satisfactory laboratory method for comparingthe duration of action of preparations of glucagon was developed. Quantitative analyses showed that all of the common amino acids in plasma were depressed by zinc glucagon. Although 3.1 moles of nonessential amino acids were removed from the peripheral circulation for every mole of essential amino acid, no statistically significant difference between the two classes of amino acids was found. The over-all reduction of blood amino acids may be largely a reflection of the gluconeogenic action of glucagon, but the variations observed among the amino acids leave doubt that the underlying mechanism involves a uniform induction of gluconeogenic enzymes; other catabolic effects of glucagon on amino acids must also be considered.
The Interaction of Diabetes and Obesity on the Regulation of Fat Mobilization in Man
Authors: Bagdade John D , Porte Daniel , Bierman Edwin L
Published: December 2014

In order to assess the influences of obesity and diabetes on the regulation of fat mobilization, plasma FFA and glycerol concentration before and during oral glucose tolerance tests were correlated with weight and glucose tolerance in forty-nine obese and nonobese nondiabetic and nonketotic mildly diabetic males.

Basal FFA and glycerol levels were directly related to the degree of carbohydrate intolerance only in the obese and correlated with weight in the diabetic subjects only. Thus, elevated basal FFA and glycerol, presumably indices of increased basal lipolysis, were found only in diabetic subjects who were also obese. Neither uncomplicated obesity nor nonketotic diabetes in the nonobese was found to be characterized by elevated basal FFA and glycerol levels.

After glutose ingestion glycerol concentrations fell at similar rates in both nondiabetic and diabetic groups, which indicated that lipolysis ceased normally in nonketotic diabetes. A delayed decline in FFA was observed in obese diabetics only, evidence consistent with impaired re-esterification in this group. These findings suggest that abnormalities in regulation of fat mobilization may become manifest in nonketotic diabetes only in the presence of obesity.
Relation of the Course of Retinopathy to Control of Diabetes, Age, and Therapeutic Agents in Diabetic Japanese Patients
Authors: Miki Eishi , Fukuda Masatoshi , Kuzuya Takeshi , Kosaka Kinori , Nakao Kiku
Published: December 2014

Follow-up results of the progression of diabetic retinopathy in 364 patients who attended the Diabetes Clinic of the Third Department of Internal Medicine (University of Tokyo) regularly for more than two years were analyzed in relation to their degree of control, age and therapeutic agents. Ophthalmologic examinations were performed by two ophthalmologists without referring to other data.

In 289 untreated cases, retinopathy at the initial visit was more frequent and more severe when known duration of diabetes was longer and initial fasting blood sugar was higher. The degree of control was judged by fasting blood sugar values determined frequently and regularly. Progression of retinopathy was significantly more frequent in the fair and poor control groups than in the good control group. In older age groups, progression, especially occurrence of new lesions, was more frequent. Sulfonylurea did not appear inferior to insulin so long as an acceptable degree of control was maintained.
Progestin Enhancement of the Plasma Insulin Response to Glucose in Rhesus Monkeys
Authors: Beck Paul
Published: December 2014

Treatment of Rhesus monkeys with pure progesterone for three weeks produced enhanced plasma insulin responses to intravenous glucose without altering glucose tolerance, and mild, but significant peripheral resistance to the hypoglycemic action of exogenous insulin. Several synthetic progestins currently employed in oral contraceptive agents also increased the plasma insulin responses to glucose. These changes were in marked contrast to the effect of acute administration of hydrocortisone, where there was a marked deterioration of glucose tolerance without any significant alteration in the plasma insulin response to glucose. From the data presented it appears that glucose tolerance remains normal following progesterone treatment because of a marked compensatory enhancement of the initial rate of release of insulin into the peripheral circulation following glucose stimulation. The mechanisms by which progestins produce these changes and the relative importance of progesterone in normal human pregnancy remains to be determined. Nevertheless, these data suggest that pure progesterone, like human placental lactogen, may be a diabetogenic factor in pregnancy and indicate that some, but not all, of the synthetic progestins may contribute to the changes in glucose and insulin metabolism observed in women taking oral contraceptive agents.
Failure of Guinea Pig Antibodies to Beef Insulin, Chicken Insulin, and Cod Insulin to Neutralize Capybara Insulin
Authors: Davidson J K , Zeigler Marcia , Haist R E
Published: December 2014

Guinea pig and coypu insulins are the only mammalian insulins known to be non-neutralizable by antibody to beef insulin. A third non-neutralizable mammalian insulin, that of the capybara (carpincho, or hydrochoerus hydrochoerus) has been identified. Capybara pancreas yielded 0.5 U. extractable insulin per gram. An amount of guinea pig antibody to beef insulin sufficient to neutralize thirty times as much beef insulin did not significantly alter the increase in glycogen content produced by pancreatic capybara insulin in the mouse hemidiaphragm in vitro. Both 50 mU. capybara insulin and 50 mil capybara insulin plus 150 mU. antibody to beef insulin when injected into mice produced about the same number of convulsions and lowered the blood glucose to about the same mean level as did 50 raU. beef insulin alone. Mice injected with 50 mU. beef insulin plus 150 mU. antibody to beef insulin did not convulse and had a mean blood glucose of 156 mg. per 100 ml. Antibody to chicken insulin and antibody to cod insulin did not significantly alter the increase in glycogen content produced by pancreatic capybara insulin in the mouse hemidiaphragm in vitro.

Capybara pancreatic extract cross-reacted with guinea pig antiserum to beef insulin in the passive cutaneous ana-phylaxis test.
Diameters of the Retinal Vessels in Diabetic and Normal Subjects
Authors: Skovborg F , Nielsen Aa V , Lauritzen E , Hartkopp O
Published: December 2014

The diameters of the retinal veins and arteries have been measured on photographs of the retina of 346 juvenile diabetic and 147 normal subjects. Statistical analysis of data was made from the findings in 266 diabetic and 129 normal subjects.

The mean width of the retinal veins in the diabetic group was about 10 per cent greater than that of the normal group (p < 0.001). About 8 per cent of the diabetic patients had vein diameters outside the normal range. The arteries of the diabetic patients were dilated on the average about 5 per cent (p > 0.001). There was a weak correlation between the known duration of the diabetes and the vein diameter.

The average vein diameter was highest in patients with retinopathy. From an analysis of the relationship between duration of diabetes and the occurrence of the retinopathy and vein dilatation it is concluded that vein dilatation is not a particularly early phenomenon in the development of the diabetic retinopathy, but rather an integrated part of the retinopathy.
In Vitro Metabolism of Glucose by Adipose Tissue from Rats Bearing a Growth Hormone Secreting Tumor (MtTW15)
Authors: Chattopadhyay D P , Akerblom H K , Martin J M
Published: December 2014

Studies were made in rats bearing the growth hormone secreting tumor (MtTW15). There was (a) a generalized depletion of depot fat with a decrease of its total fatty acidcontent, and increased rate of lipolysis, (b) a rise in the fasting levels of serum FFA detectable only during theearly period of tumor development, and (c) a severe depression of the in vitro metabolism in adipose tissue of glucose to CO2 and fatty acids. The addition of insulin could not restore the lowered values to the basal level of the controls.

These findings indicate that chronically elevated levels of GH decrease the glucose utilization and insulin responsivenessof rat adipose tissue and suggest that rats bearing this particular tumor constitute a suitable experimental model for studies on the metabolic effect of hypersommatotropism
Insulin Storage and Release in Rats Bearing Growth Hormone Secreting Tumors
Authors: Peake Glenn T , McKeel Daniel W , Mariz Ida K , Jarett Leonard , Daughaday William H
Published: December 2014

The effects of chronic hypersomatotropism on pancreatic islet function were studied in rats bearing the growth hormone secreting tumor MtTW15. These rats did not become hyperglycemic and minimally hyperinsulinemic in the fed state following prolonged massive elevations of serum growth hormone. Islets from tumor-bearing rats were grossly larger and beta cells more granulated than in control rats by light microscopy. Electron microscopy confirmed the increase in cell cytoplasm and increased number of beta granules per cell. Isolated islet preparations from tumor-bearing rats contained four times the insulin found in control rats. Fed control and tumor-bearing rats had comparable serum glucose and immunoreactive insulin concentrations after glucose intragastrically and tolbutamide intravenously. After a forty-eight-hour fast the tumor-bearing rats had higher serum immunoreactive insulin than controls and their insulin levels were higher after glucose and tolbutamide than controls. Some of the tumor-bearing rats became hypoglycemic during the forty-eight-hour fast. The increased stored insulin in the tumor-bearing rats was mobilized by a combination of the individually potent insulinogenie stimuli theophylline and glucagon.
Effects of Oral and Intravenous Glucose Loading in Thyrotoxicosis: Studies of Plasma Glucose, Free Fatty Acid, Plasma Insulin and Blood Pyruvate Levels
Authors: Doar J W H , Stamp T C B , Wynn V , Path F C , Audhya T K
Published: December 2014

Plasma glucose, NEFA, insulin and blood pyruvate levels before and after oral/intravenous glucose administration have been compared in a group of twenty-eight thyrotoxic subjects and a group of control subjects matched for age, sex and degree of obesity.

The mean fasting plasma glucose level was elevated, and 44 per cent of oral and 24 per cent of intravenous glucose tolerance tests were impaired in the thyrotoxic group.

The mean plasma insulin level in the thyrotoxic group was elevated both before and after oral and intravenous glucose administration.

Mean fasting plasma NEFA levels were elevated in the thyrotoxic group but fell to normal levels following glucose administration.

Mean fasting blood pyruvate levels were similar in control and thyrotoxic groups but abnormally elevated levels were observed in the latter following oral glucose administration.

Mean fasting serum triglyceride levels were similar in both groups, but the mean fasting serum cholesterol was significantly lower in the thyrotoxic subjects.

The possible significance of these abnormalities is discussed.
Levels of Plasma Insulin During Cortisone Glucose Tolerance Tests in “Nondiabetic” Relatives of Diabetic Patients: Implications of Diminished Insulin Secretory Reserve in Subclinical Diabetes
Authors: Rull Juan A , Conn J W , Floyd John C , Fajans Stefan S
Published: December 2014

Plasma levels of insulin were determined during standard oral glucose tolerance tests and during cortisone glucose tolerance tests performed upon “nondiabetic” subjects (normal standard GTT) who were first degree relatives of diabetic patients. The standard test was also performed upon mildly diabetic patients and healthy control subjects. The results of the standard glucose tolerance test (levels of plasma insulin and blood glucose) did not differentiate the relatives with positive cortisone glucose tolerance tests (subclinical diabetes) from those with negative cortisone glucose tolerance tests although in both groups levels of plasma insulin were lower than in healthy subjects. However, the results of the cortisone glucose tolerance test did distinguish the group with subclinical diabetes from the relatives with negative tests since the secretion of insulin was delayed and insufficient in the subjects with positive testsl During the standard test patients with mild “maturityonset” diabetes showed delayed and insufficient secretion of insulin as compared to the healthy subjects.

It is concluded that during the cortisone glucose tolerance test, “nondiabetic” relatives of diabetic patients who have positive tests (subclinical diabetes) exhibit a defect in the secretion of insulin which distinguishes them from subjects with negative tests. This defect is similar in pattern to that observed in mildly diabetic patients during the standard test. This deficiency in the secretion of insulin represents an important part of the mechanism which induces a positive cortisone glucose tolerance test.

This demonstration that, in some relatives of diabetics, a grossly normal standard glucose tolerance can exist at a time when decreased reserve insulin secretory capacity can be measured, justifies a careful evaluation of whether some form of therapy is indicated at this stage of the disease (subclinical diabetes) and, if so, what form it should be. The meaning of the statistically significant subnormal response of plasma insulin to a standard glucose load in relatives with negative cortisone glucose tests is not yet apparent. Since in them the reserve insulin secretory capacity, as measured by the CGTT, remains intact, it is premature, pending additional data, to raise the question of possible treatment of this group.
Studies on the Site and Mechanism of Action of Phenformin: II. Phenformin Inhibition of Glucose Transport by Rat Intestine
Authors: Kruger Fred A , Altschuld Ruth A , Hollobaugh Samuel L , Jewett Barbara
Published: December 2014

The effect of oral phenformin on the active transport of glucose by everted sacs of rat intestine was investigated. Pretreatment of the animals with a single dose of the drug resulted in an inhibition of active transport. A log-dose relationship was found in the range studied (5 to 150 mg./kg.). These findings could explain the observation that phenformin increases the tolerance to orally administered glucose but has no effect on intravenous glucose tolerance in humans.
The Glucose Tolerance Test and the Response of Intraocular Pressure to Topical Corticosteroids
Authors: Becker Bernard , LeBlanc Raymond P
Published: December 2014

Glucose tolerance tests were performed on 100 patients classified as high (gg) intraocular pressure responders (> 31 mm. Hg) to topical dexamethasone and compared with 100 matched patients classified as low (nn and ng) intraocular pressure responders. The sum of plasma glucose values at 0, 1, 2, and 3 hours was distributed in approximately Gaussian fashion for the poor intraocular pressure responders (mean 450 ± 70 (σ) mg./100 ml. Plasma glucose sums of 600 mg./100 ml. or more were found in 21 per cent of the gg patients but in only 3 per cent of the nnng group.
Clinical Remission in Diabetes Mellitus: Studies of Insulin Secretion
Authors: Genuth Saul M
Published: December 2014

Two cases of remittent diabetes following ketoacidosis are described. The return of plasma insulin rises after glucose, tolbutamide, and glucagon was shown, documenting the temporary recovery of beta cell function during remission.