bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes Mellitus and Periodontal Disease
Authors: Finestone Albert J , Boorujy Samuel R
Published: December 2014

One hundred and eighty-nine dentulous patients with diabetes mellitus and sixty-four patients believed free of diabetes were examined for periodontal disease. Certain variables were measured and related by computer analysis to the degree of observed gingival pathology. The findings indicate that the prevalence and severity of periodontal disease are increased in the diabetic patient. In addition, the periodontal index was related in positive fashion to age, duration of known diabetes, diabetic complications, and variation of blood sugar levels.
Insulin Response during Tularemia in Man
Authors: Shambaugh George E , Beisel William R
Published: December 2014

Serum insulin concentrations were measured serially in seven nondiabetic subjects following a rapid intravenous glucose load during a preinfection control period, during early clinical respiratory tularemia, and again in convalescence following therapy. Within twenty-four hours of onset of clinical illness the rate of glucose disappearance from the blood had diminished significantly (p<0.05). At the same time there was a brisk rise in insulin levels reaching higher peak concentrations and falling more slowly than the response observed during the preinfection control period. The pattern during clinical illness was different from that described after intravenous glucose loading in maturity onset diabetes or obesity and may have been influenced by glucocorticoid excess. Increased whole blood pyruvate concentrations following glucose loading during clinical illness were compatible with heightened glucocorticoid ction. The magnitude of insulin clinical illness was significantly increased (p<0.02) and was directly related to height of fever In contrast, the rate of glucose disappearance was inversely related to fever. The inverse relationship of the magnitude of insulin output to the rate of glucose reappearance suggested a peripheral inhibition of insulin action during infection. Although fever may have played a role during acute illness, the persistence of an abnormal insulin response in one patient during convalescence suggested that this change was not dependent upon fever alone. Other factors that may have contributed to the peripheral inhibition of insulin action during clinical illness are briefly discussed.
Biological Properties of a Transplantable Islet-cell Tumor of the Golden Hamster: I. Histology and Histochemistry
Authors: Grillo T Adesanya I , Whitty Albert J , Kirkman Hadley , Foa Piero P , Kobernick Sidney D
Published: December 2014

This paper describes some histologic and histochemical characteristics of an easily transplantable islet-cell tumor of the Syrian hamster. The presence of insulin was demonstrated by means of fluorescent antibody and immunoassay technics. A positive histochemical reaction for tryptophan suggests, but does not prove, the presence of small amounts of glucagon. It is suggested that the tumor may be a useful tool for biologic studies.
Insulin Release After ACTH, Glucagon and Adenosine-3′-5′-Phosphate (Cyclic AMP) in the Perfused Isolated Rat Pancreas
Authors: Sussman Karl E , Vaughan Gary D
Published: December 2014

An isolated rat pancreas preparation has been employed for the study of insulin Secretion. The preparation consists of the pancreas and the duodenum in which the thoracic aorta is cannulated for arterial inflow and the portal vein cannulated to collect the venous effluent. The administration of ACTH, glucagon and cyclic AMP will increase the secretion of insulin from the isolated perfused pancreas. Theophylline was infused into the pancreas with glucagon and compared with glucagon alone. Theophylline did not have any effect on altering insulin secretion from the pancreas nor did it potentiate the glucagon-induced insulin release. While glucagon, ACTH, and cyclic AMP all stimulate insulin secretion, there is no definitive evidence that the effect of glucagon or ACTH on the beta cell is due to intracellular generation of cyclic AMP.
Abnormal Response to Valsalva Maneuver in Diabetics: Relation to Autonomic Neuropathy
Authors: Nathanielsz P W , Ross E J
Published: December 2014

Changes in heart rate on performing the Valsalva maneuver can easily be monitored with an EKG and a modified sphygmomanometer. Observations have been made on twenty-four diabetics and their matched controls. Impairment of cardiovascular reflexes demonstrated by this technic correlates well with the presence of other complications of diabetes, especially neuropathy. Impairment of response increases exponentially with duration of the disease but not with age. Assessment of the degree of autonomic nervous involvement in diabetic patients is of assistance in their management. The procedure employed has proved satisfactory in gaining necessary information rapidly with easily available apparatus.
Urine Sugar Determination by the Two-drop Clinitest Method
Authors: Belmonte Mimi M , Sarkozy Eva , Harpur Eleanor R
Published: December 2014

Erroneous urine tests for sugar can result from many causes. The Clinitest method carried out in the usual recommended way (five drops of urine) is accurate in the 0 to 2 per cent sugar concentration range. Over 4 per cent, there is a reversal of color which can be mistaken for 0.75 or 1 per cent and which is referred to as “pass through.” When two drops of urine are used instead of five, the range of Clinitest change is extended from 0 to 5 per cent and the “pass through” delayed until a concentration over 10 per cent sugar is reached. In 191 urines from diabetic children, the confusing “pass through” was found to occur seventy times when the urine was tested by the “five-drop method.” It did not occur in testing the same urines using the “two-drop method.” Quantitative chemical analysis established the range of these two methods. It is recommended that the “two-drop method” should replace the “five-drop method.”
“What Is Inherited – What Is Added” Hypothesis for the Pathogenesis of Diabetes Mellitus
Authors: Cerasi Erol , Luft Rolf
Published: December 2014

A working hypothesis for the pathogenesis of diabetes mellitus has been drawn up which has found partial support in experimental data in human subjects. An impaired insulin response, common to all types of diabetes including prediabetes, has been brought to attention as a major possible inherited pathogenetic component. Other factors besides the impaired insulin production have been suggested as significant in the subsequent development of manifest diabetes.
Nature of Islet-cell Innervation in the Cat Pancreas
Authors: Esterhuizen A C , Spriggs T L B , Lever J D
Published: December 2014

Enzyme histochemical and autoradiographic methods provided evidence for adrenergic and cholinergic innervation of both alpha and beta cells in the islets of Langerhans of the cat.
Tranylcypromine: A Potent Insulin Secretagogue and Hypoglycemic Agent
Authors: Bressler Rubin , Vargas-Cordon Mario , Lebovitz Harold E
Published: December 2014

The intraperitoneal administration of tranylcypromine, a nonhydrazine monoamine oxidase inhibitor, to mice resulted in a rapid and marked stimulation of insulin secretion, which was followed at 60 to 90 min. by profound hypoglycemia. The conversion of lactate to blood glucose was markedly depressed by the drug. Other monoamine oxidase inhibitors tested had no effect on insulin secretion or blood glucose. The tranylcypromine stimulated insulin secretion was not affected by prior administration of reserpine but was inhibited by prior administration of MJ 1999, a β-adrenergic receptor blocker. Tranylcypromine stimulated insulin secretion was augmented by prior administration of phentolamine, an α-adrenergic receptor blocker. Prostaglandin E1 administration stimulated insulin secretion and this effect was also inhibited by MJ 1999. Tranylcypromine stimulation of insulin secretion from the pancreas was also obtained in vitro. The role of α and β-adrenergic receptors in the control of insulin secretion in the pancreatic islets is discussed.
Hypoglycemic Action of Monoamineoxidase Inhibitors (MAOI'S)
Authors: Adnitt P I
Published: December 2014

Insulin tolerance tests were carried out in six depressed patients before and after administration of mebanazine and in six before and after administration of phenelzine. There was no change in fasting blood glucose with treatment, but glucose levels after insulin were significantly lower during treatment with both these hydrazine MAOI's. There was no effect on the changes in pulse, blood pressure and sweating in response to hypoglycemia.

The hypoglycemic action of mebanazine was further investigated in five patients from a diabetic clinic who were poorly controlled on sulfonylurea treatment and who were not depressives. Glucose tolerance was improved in all cases five weeks after addition of mebanazine, 20 mg. daily to the regime, and there was a significant (p = 0.031) reduction in blood glucose at all times of the glucose tolerance test. The mean glucose tolerance of four patients showed deterioration after discontinuation of mebanazine. Glucose tolerance did not improve in five patients treated with placebo.

Insulin sensitivity of depressed patients was increased during administration of hydrazine MAOI's and a hypoglycemic action in diabetes was demonstrable in the absence of a depressive illness.
Measurement of Insulin Secretion: A Review of Current Methods
Authors: Wright Peter H
Published: December 2014

The principal methods currently used to measure insulin secretion are briefly reviewed. From observed changes in concentration of immunoreactive insulin in plasma, insulin secretion in vivo can be more accurately assessed and smaller changes in secretion rate detected using pancreatic rather than systemic venous samples of blood. Measurement of secretion in vitro is complicated by the release from acinar tissue of a substance which destroys secreted insulin and similar polypeptides but whose action can be reduced or circumvented. When interpreting the effects of stimulants and inhibitors, it has also to be remembered that they could act indirectly through their actions upon other tissues of the body or upon cells other than the beta-cells of the pancreatic islets. These and other factors should be taken into account when interpreting data obtained by the several practical methods now used to study the insulin secretory process.
Biochemical Basis of the Sulfonylurea-induced Antabuse Syndrome
Authors: Podgainy Helen , Bressler Rubin
Published: December 2014

The antabuse reaction, seen in patients imbibing alcohol while being treated with an antidiabetic sulfonylurea, is thought to be due to either an increase in acetaldehyde levels or an alteration in the metabolism of serotonin. Both can occur through an inhibition of aldehyde dehydrogenase. The oral antidiabetic sulfonylureas, chlorpropamide and tolbutamide, were found to be noncompetitive inhibitors of this enzyme. Acetaldehyde, a metabolite of ethanol, can competitively inhibit aldehyde dehydrogenase. Moreover, the oxidation of ethanol reverses the DPN/DPNH ratio so that the favored pathway of serotonin metabolism is altered, resulting in a decrease of 5-hydroxyindoleacetic acid (5-HIAA) and an increase of 5-hydroxytryptophol. Thus, ethanol augments the action of the sulfonylureas. Whether the syndrome results from an accumulation of acetaldehyde due to a block in ethanol metabolism, or whether it is a result of an alteration in the metabolism of serotonin, the noncompetitive inhibition of aldehyde dehydrogenase by the sulfonylureas, coupled with the actions of ethanol, may be considered as a potential cause.
Cerebral Edema, Diabetes Insipidus, and Sudden Death during the Treatment of Diabetic Ketoacidosis
Authors: Taubin Howard , Matz Robert
Published: December 2014

A young diabetic patient with ketoacidosis responding to standard treatment abruptly developed pulmonary edema, apnea, coma, cardiac arrythmias and diabetes insipidus. At autopsy, cerebral edema and neuronal degeneration were present. In the hypothalamus many neurones were absent. Similar cases have been reported, but the pathogenesis of the syndrome is not understood. The present patient received large amounts of sodium bicarbonate, and significant potassium deficiency may have been present.
Radioimmunoassay of Insulin A and B Chains in Normal and Diabetic Human Plasma
Authors: Meek Joseph C , Doffing Kenneth M , Bolinger Robert E
Published: December 2014

A sensitive radioimmunoassay has been developed for the detection of the insulin chains in the plasma of normal and diabetic human subjects. The S-sulfonated derivatives of bovine insulin A and B chains were purified, iodinated with high specific activity and used for immunoassay by the double antibody technic. Twelve noninsulin-requiring diabetic and nine normal, nonobese subjects were studied before and during a four-hour oral glucose tolerance test by determination of plasma immunoreactive insulin, A chain and B chain. The results of our data indicate that: detectable levels of both insulin A and B chain do exist in human plasma; A chain is present in higher concentration than B chain in both normal and diabetic plasma; and greater than normal amounts of A chain can be detected in diabetic subjects and the concentration increases during a glucose tolerance lest in these patients.
Relationship between Meal Size and Frequency and Plasma Insulin Response in Man
Authors: Cohn Clarence , Berger Sheldon , Norton Margaret
Published: December 2014

The effect of varying the size of a meal on plasma insulin was determined in eight normal male adults. The effect of consuming one half of a meal at 0 time and one half at two hours later was also studied. Each subject was studied on four days, one day when he consumed a whole meal (580 calories) of natural foodstuffs; one day, one-half the meal; one day, one quarter of the meal, and one day when he consumed one half the meal at 0 time and the remainder two hours later. When fractions of the meals were ingested, all ingredients were decreased proportionately. As meal size was increased, a log-dose relationship was observed to characterize the comparison of meal size ingested to plasma insulin response. When on the fourth day the subjects consumed the meal in fractions, the mean sum of the plasma insulin responses was identical to that observed when the meal was eaten at one time. The results suggest that over a four-hour period, the plasma insulin response is a function of the magnitude of the load of calories requiring disposition and that the response does not appear to be influenced by the frequency with which the calories are ingested.
Oxidation of Glucose, Acetoacetate, and Palmitate in Brain Mince of Normal and Ketotic Rats
Authors: Openshaw Harry , Bortz Walter M
Published: December 2014

The effect of the addition of acetoacetate or fatty acids on the oxidation of glucose, and vice versa, in rat brain minces was studied. The results suggested that acetoacetate spares the oxidation of glucose by rat brain, but only slightly. Ketosis induced by starvation or fat feeding had little effect on this sparing action. Acetoacetate appeared to lower glucose oxidation, at least in part, by diversion of a higher portion of the glucose to lactate.

The oxygen consumption was essentially the same in the minces prepared from normal or ketotic rats. Addition of glucose to the medium containing acetoacetate increased oxygen consumption and acetoacetate oxidation to the same degree. In contrast, palmitate oxidation was decreased when glucose was added to the medium.

These in vitro studies indicate that glucose is the preferred substrate for rat brain energy production in both the normal and ketotic states.
Metabolic Effects of the Biguanides and Possible Mechanism of Action
Authors: Jangaard N O , Pereira J N , Pinson Rex
Published: December 2014

The relationship between the biguanide inhibition of oxidations and their effect on glucose metabolism in vitro has been investigated. We found a good correlation between the concentration of biguanide causing a halfmaximal inhibition of pyruvate oxidation (Ki) and the concentration eliciting a half-maximal stimulation (Ks) of glucose uptake in several tissues from rat, guinea pig and pigeon. Guinea pig epididymal fat pad was the most sensitive tissue tested. Gluconeogenesis by minced guinea pig liver was inhibited by the biguanides. The ability of the biguanides to inhibit gluconeogenesis correlated well with their ability to inhibit pyruvate oxidation. Inhibition of oxidations by the biguanides does not appear to be a result of a direct inhibition of the enzymes catalyzing these oxidations but seems to be secondary to a primary effect on the coupled processes of electron transport and oxidative phosphorylation. We have summarized and discussed objections to the theory that the metabolic actions of the biguanides are a result of their inhibition of oxidative processes. Our conclusion is that the inhibition of oxidations caused by the biguanides is directly related to their metabolic and hypoglycemic effects.
Effects of Glucagon and Tolbutamide on Plasma Insulin Levels in Children with Ketoacidosis
Authors: Chiumello Giuseppe , Guercio Maria Jose Del , Bidone Giovanni
Published: December 2014

The concentration of immunoreactive insulin in plasma has been determined following administration of tolbutamide and glucagon in seven children with newly diagnosed diabetic ketoacidosis. The basal plasma insulin levels were low, notwithstanding concomitantly high blood glucose levels. The plasma insulin concentration was increased by glucagon but not tolbutamide stimulation. These data suggest that a different mechanism of insulin release is induced by tolbutamide and glucagon.
Role of Beta-Adrenergic Receptors in Counterregulation to Insulin-induced Hypoglycemia
Authors: Abramson Eugene A , Arky Ronald A
Published: December 2014

Since beta-adrenergic blockade dampens the rebound of plasma glucose after insulin-induced hypoglycemia in man but does not affect epinephrine-stimulated hepatic glycogenolysis, studies were undertaken to define further the metabolic role of beta-adrenergic stimulation, particularly its participation in the induction of peripheral insulin resistance by epinephrine. In in vitro studies, propranolol, a specific beta-adrenergic blocker, was shown to prevent both epinephrine and isoproterenol from inducing inhibition of insulin-stimulated glucose uptake by rat hemidiaphragm. Methoxamine, an alpha-adrenergic stimulator, did not alter insulin-stimulated glucose uptake. In man, propranolol blocked the late rise of blood lactate levels which occurs during insulin tolerance tests, indicating that muscle glycogenolysis was prevented and suggesting that propranolol prevents epinephrine from inducing peripheral insulin resistance. This might in part account for the prolonged hypoglycemia observed in propranolol-insulin tolerance tests.
Accuracy of Urine Testing for Sugar and Acetone by Hospital Ward Personnel
Authors: Dobson Harold L , Shaffer Rose , Burns Rachel
Published: December 2014

1. The determination of urinary sugar and acetone by ward nursing service personnel is often inaccurate. In 12 per cent of the tests reported in this study the level of inaccuracy could lead to significant errors in management.

2. Lack of familiarity with the test procedures and personal bias were two major factors associated with these inaccuracies. Both may be reduced by better training and supervision.

3. Limitations in the test procedures are also a major factor. These cannot be eliminated completely but the twodrop Clinitest method for urine sugar offers several advantages and should be used in preference to the five-drop method.
Gastric Cancer Containing Insulin and Associated with Hypoglycemia
Authors: Miyabo Susumu , Fujimura Akira , Matsuda Tamotsu , Murakami Mototaka
Published: December 2014

A patient with gastric cancer associated with hypoglycemia is described. Immunoassay of acid alcohol tissue extract revealed the presence of 7.6 mU. insulin per gram wet tissue weight in the primary tumor which weighed 10 gm. No insulin was detected in the hepatic metastasis. The concentration of pancreatic insulin was decreased and the serum insulin level was not elevated. Tissue insulinase activity was virtually absent in the primary tumor, whereas the hepatic metastasis showed activity comparable to that of normal liver. It is difficult to assume, however, that the release of insulin from the primary tumor, which contained such small quantities of the hormone, could be the Bole cause of hypoglycemia. An additional mechanism(s) must have been involved in the causation of hypoglycemia in this patient.
Effects of Exogenous Insulin on the Rate of Fatty Acid Synthesis and Glucose C-14 Utilization in the Twenty-day Rat Fetus
Authors: Clark C M , Cahill G F , Soeldner J S
Published: December 2014

Serum IRI (immunoreactive insulin) in twenty-day fetuses from mothers fed ad libitum exceeded maternal levels. Increasing maternal IRI produced by injection of exogenous insulin or by intravenous glucose loading did not produce significant changes in fetal IRI. The twenty-day pregnant rat in the basal state distributed relatively more C-14 from radio glucose into lipid and glycogen and relatively less into protein than a nonpregnant control under similar conditions. Incorporation of C-14 from radioglucose was augmented by exogenous insulin at fifteen minutes into lipid in maternal liver and adipose tissue, protein into liver and glycogen in muscle. Neither the incorporation of C-14 into lipid, glycogen, or protein from radioglucose nor the incorporation of H3 (from H32O) into fatty acids was influenced by exogenous insulin in the fetus. This was true even when the insulin was injected directly into the fetus. On the other hand, fetal incorporation of radioglucose into glycogen was augmented significantly by an acute glucose load. The data suggest that although fetal serum contains significant concentrations of insulin derived from fetal (β-cells, the exact metabolic role of this insulin in the fetus is unclear.
A Rapid Bedside Method of Monitoring Blood Glucose in Diabetic Hyperglycemia
Authors: Stephens A D
Published: December 2014

A rapid bedside method is described for estimating blood glucose levels in the range 200 to 2,000 mg. per 100 ml. The method employs Dextrostix and a dilution technic using a Mantoux syringe and isotonic saline.
Effect of Storage Temperature on Stability of Commercial Insulin Preparations
Authors: Storvick Waldemar O , Henry Harry J
Published: December 2014

The effects of storage on stability of six types of commercial insulins have been studied at 5°, 25°, 37°, and 50° C. for periods up to thirty-six months. Samples of insulin from thirty-two batches at concentrations of 40 and 80 U. per ml. were used.

Use of the radioimmunoassay made it practical to perform the large number of potency determinations required to obtain the data in the present report. These data show that no appreciable loss of potency occurred in any of the insulins during thirty months of storage at 5° C. At higher temperatures extent of potency loss was influenced by length of storage and type of insulin. In general, all modified insulins studied were more stable than Regular insulin. Under the same conditions Protamine Zinc and NPH insulins were more stable than the Lente insulins.

The biological reaction (duration of action) of the modified insulins which had beenstored for twenty-four months at 5°C. were compared with freshly prepared samples. No significant changes in the response curves characteristic for each insulin type were observed. Potency determination by the U.S.P. rabbit assay compared satisfactorily with data obtained by radioimmunoassay
Guinea Pig Anti-Insulin Serum: Adjuvant Effect of H. Pertussis Vaccine
Authors: Wright Peter H , Makulu David R , Posey Iva J
Published: December 2014

After three injections at weekly intervals of insulin in a water-in-oil emulsion containing H. pertussis vaccine, guinea pigs were given the same inoculum containing no vaccine at intervals of four weeks. At the first bleeding after eight weeks, most animals yielded serum binding more than 1.0 U. insulin per milliliter; the mean binding capacities of sera from animals in four out of seven groups exceeded 4.5 U. insulin per milliliter. Over eighteen months, five groups totalling 136 animals yielded 3,000 ml. serum, the pooled sera from each group binding 2.7 to 4.8 U. insulin per milliliter. It is concluded that use of H. pertussis vaccine offers a reliable method for the production of large volumes of potent anti-insulin serum.
The Later Life of the Diabetic Amputee: Another Look at Fate of the Second Leg
Authors: Whitehouse F W , Jurgensen Craig , Block Melvin A
Published: December 2014

Studies were made of sixty-seven diabetic patients who had lost one leg to gangrene. At the time of the study, forty-seven were dead and twenty lived. Only five patients inthe former group and four in the latter had lost their “second leg.” Early death from the effects of a generalized arteriosclerotic process accounts for the small number of double amputees. A diabetic amputee will probably lose his life before he loses his “second leg.”
A Method for the Immunoassay of Insulin
Authors: Wright Peter H , Makulu David R , Malaisse Willy J , Roberts Nancy M , Yu Pao-Lo
Published: December 2014

A method is described for the assay of insulin. It involves pre-incubation of insulin under assay with an excess of guinea pig anti-insulin serum and subsequent incubation of the partially neutralized serum with an excess of unlabeled and/or I-131-labeled bovine insulin. If no more than about half of the antibodies in the serum are neutralized during pre-incubation, then the amount of bovine insulin bound during incubation decreases linearly and in proportion to the amount of pre-incubated insulin. Such a linear relationship was obtained with nine samples of pooled serum from uve groups of guinea pigs and was shown to be applicable over a wide range of serum and insulin concentrations. Since neutralized acid-alcohol affected the assay only when present in relatively high concentrations, the method has been applied to neutralized acid-alcohol extracts of pancreatic tissue without removal or excessive dilution of the alcohol. It is applicable at concentrations of insulin to be found in blood and is therefore a potentially simple and rapid method which would not require the use of labeled insulin of high specific activity. The uses and limitations of the method are discussed.
Control of Pancreatic Glucagon Secretion by Glucose
Authors: Ohneda Akira , Aguilar-Parada E , Eisentraut Anna M , Unger Roger H
Published: December 2014

Recent questions concerning the role of glucagon as a hormone of “glucose need” prompted this evaluation of glucose-glucagon relationships. To obviate certain problems relating to the sensitivity and specificity of the glucagon radioimmunoassay of peripheral venous plasma, glucagon was assayed in pancreatic venous effluent plasma obtained from conscious dogs with indwelling catheters in the pancreaticoduodenal vein. The effect of change in glucose concentration upon the pancreaticoduodenal vein glucagon concentration was determined.

Insulin induced hypoglycemia was uniformly associated with a rise in pancreaticoduodenal vein glucagon concentration to a peak of 5.7 mμg./ml. at thirty minutes. The hyperglucagonemia continued intermittently during the hypoglycemic period but fell promptly during hyperglycemia induced by rapid injection of glucose.

Hyperglycemia, induced in fifteen dogs by glucose infusion, was accompanied by a decline of glucagon from 2.7 to 1.8 mμg./ml. Cataglycemia, induced by rapid termination of a glucose infusion, produced a rise of glucagon in three of six dogs.

Stimulation of glucagon secretion by hyperaminoacidemia was blocked by hyperglycemia induced by glucose infusion. The effect of starvation upon twenty-four-hour secretion of glucagon could not be determined in these studies. Wide variations in pancreaticoduodenal vein glucagon concentration made meaningful comparison of day-to-day changes impossible.

A statistically significant negative correlation was observed between rapidly induced change in plasma glucose concentration and change in pancreaticoduodenal vein glucagon levels. The findings are compatible with the view that glucagon is a hormone of glucose need, which probably functions in the moment-to-moment regulation of blood glucose homeostasis and the maintenance of the so-called “normal” blood glucose limits.
Insulin Immunoassay by Back-titration Using Alcohol Precipitation of Insulin-Antibody Complexes
Authors: Makulu David R , Vichick Diana , Wright Peter H , Sussman Karl E , Yu Pao-Lo
Published: December 2014

A method is described in detail for the assay of insulin in plasma or serum. It involves titration with labeled insulin of reactive insulin antibodies remaining after preincubation of the sample under assay or of standard solutions of insulin with an excess of guinea pig anti-insulin serum. Labeled insulin bound by antibodies in the assay is precipitated in the presence of alcohol (75 per cent, v/v) at room temperature, unbound labeled insulin then remaining in solution. The technic is simple and assays can be carried out in a few hours. It is shown that individual results are amenable to statistical assessment and suggested that the sensitivity of the method is only limited by the specific activity of the labeled insulin used.
Significance of Human Plasma Insulin Sephadex Fractions
Authors: Goldsmith Stanley J , Yalow Rosalyn S , Berson Solomon A
Published: December 2014

Fifty-nine samples taken from lean and obese healthy subjects and from patients with diabetes mellitus, myotonic dystrophy, and islet cell adenoma after the administration of oral or intravenous glucose or other insulin secretogogues were fractionated on Sephadex G-50 columns. Eluates corresponding to zones of elutions of porcine pro insulin (“big insulin”) and Regular insulin were assayed for insulin by radioimmunoassay using crystalline human insulin as standard and porcine insulin-I-125 as tracer. In four samples from one patient with islet cell adenoma the big insulin fraction composed 24 to 55 per cent of the apparent insulinimmunoreactivity but in no other case did big insulin exceed 20 per cent of the total and in fifty-one of the fifty-five samples other than from the patient with insulinoma, big insulin contributed less than 15 per cent to the total apparent immunoreactive plasma insulin.
Hyperglycemic, Hyperosmolar, Nonketoacidotic Diabetes: A Complication of Steroid and Immunosuppressive Therapy
Authors: Spenney J G , Eure C A , Kreisberg R A
Published: December 2014

Two cases of hyperglycemic, hyperosmolar, nonketoacidotic diabetes are reported. Both had renal disease and were receiving corticosteroids and azathioprine. A third patient with hepatitis receiving corticosteroids alone and developing ketoacidosis is described also. The syndrome of hyperglycemic coma is discussed and speculations on the role of steroids and azathioprine are made.
Insulin and Ketone Responses to Ingestion of Medium and Long-chain Triglycerides in Man
Authors: Pi-Sunyer F Xavier , Hashim Sami A , Itallie Theodore B Van
Published: December 2014

The effects of medium chain triglyceride (MCT), corn oil, and water on serum glucose, ketones, and immunoreactive insulin (IRI) were compared. Fourteen normal subjects ingested 1 gm. per kg. of MCT (composed principally of C8 and CIO fatty acids) and on another occasion an equal volume of water. After water ingestion, glucose, ketones, and IRI did not change appreciably up to five hours. After MCT, a significant rise in serum ketones and IRI was associated with a slight fall in serum glucose. Fourteen normal subjects ingested 1 gm. per kg. corn oil, and on another occasion an equal volume of water. Serum glucose, ketone and IRI concentrations again did not change up to five hours after ingestion of water. After corn oil, no significant rise in ketones occurred. There was a small rise in IRI and a slight fall in glucose. In the eight subjects in whom MCT, corn oil and water were compared a certain degree of insulin secretory response was obtained after MCT and corn oil but not after water ingestion. However, the IRI response after MCT was highest. The rise in IRI without a corresponding change in serum ketones after ingestion of the long chain triglyceride might be attributed to a gastrointestinal β-cytotropic effect. The mechanism of IRI stimulation by MCT also has been related to MCT-induced hyperketonemia and possibly toa direct effect on insulin secretion of small amounts of octanoate in peripheral blood.
Relative Effects of Pregnancy, Human Placental Lactogen and Prednisolone on Carbohydrate Tolerance in Normal and Subclinical Diabetic Subjects
Authors: Kalkhoff R K , Richardson B L , Beck P
Published: December 2014

Six subclinical diabetic postpartum women with normal standard glucose tolerance tests (GTT) but diabetic responses during prednisolone glucose tolerance tests (PGTT) had a third GTT performed after an overnight infusion of human placental lactogen (HPL). Similar studies were done on six control postpartum women with normal GTT and PGTT. HPL infusions produced plasma levels of the hormone that were comparable to concentrations observed in late pregnancy.

In the control group HPL infusion had minimal effects on GTT, and no significant changes of plasma immunoreactive insulin (IRI) were observed. Higher, though normal, glucose levels during PGTT were associated with corresponding elevations of IRI.

HPL infusion, like prednisolone administration, induced diabetic curves in the subclinical diabetic subjects, and IRI levels did not rise significantly above corresponding GTT levels until the second hour even though abnormal hyperglycemia was established between one-half and one hour. Both hormones increased fasting plasma glucose levels, but only prednisolone elevated fasting levels of nonesterified fatty acids.

Three control and three diabetic women were also studied prepartum. Neither pregnancy nor postpartum HPL infusion altered GTT in the normal group. HPL administration to the diabetic subjects induced deterioration of carbohydrate tolerance that was more pronounced than that observed prepartum. In both groups plasma IRI was higher during prepartum testing.

These observations suggest that normal women resist degrees of diabetogenic stress that produce abnormal GTT in subclinical diabetic patients. The latter group tolerated pregnancy better than postpartum HPL or prednisolone administration presumably because of the greater adaptive hyperinsulinemia that occurred during gestation.
Immunology Conformation and Biological Activity of Insulin
Authors: Arquilla Edward R , Bromer William W , Mercola Daniel
Published: December 2014

Evidence is presented that insulin antibodies produced by strain 2 guinea pigs bind preferentially to antigenic determinants related to the N-terminal B chain, N-terminal A chain, and lysine at position B-29. Strain 13 antibodies appear to bind preferentially to antigenic determinants involving the C-terminal A and C-terminal B chains. It appears that the C-terminal A chain and C-terminal B chain, in close proximity to each other, form a center rich in aromatic amino acids. This center appears to be directly related to the antigenic determinants with which the strain 13 antibodies combine, but in addition, is also important for the conformation of distant antigenic determinants. Insulin derivatives which have the greatest distortion of antigenic determinants (desoctopeptide, iodinated, and triconjugated fluorescent insulin) also have negligible biologic insulin activity. Desalamine-desasparagine insulin and diconjugated fluorescent insulin which by their immunologic reactivity appear to have distortions of antigen determinants of an intermediate degree have trace amounts of biologic activity. The insulin derivative with the least distortion of antigenic determinants (monoconjugated fluorescent insulin) had more biologic insulin activity than any of the derivatives studied.

Physical measurements involving circular dichroism and ultra centrifugal analysis confirm the immunologic observations concerning the conformations of insulin and the insulin derivatives.

These studies show that any change in conformation results in a proportionate decrease of biologic activity of insulin. Therefore, the molecular mechanism of insulin action probably involves a complementary fit with a site either on or with insulin responsive cells.
Improved Glucose Disappearance Following Repeated Glucose Administration: Serum Insulin, Growth Hormone and Free Fatty Acid Levels During the Staub-Traugott Effect
Authors: Szabo Andrew John , Maier Jacqueline J , Szabo Olga , Camerini-Davalos Rafael A
Published: December 2014

The Staub-Traugott effect, the phenomenon of improved tolerance to repeated glucose administration, was investigated in fifteen healthy volunteers. Two glucose loads were administered intravenously forty-six minutes apart. Blood samples were taken periodically after each glucose infusion. The second glucose load was given immediately after the first sampling period. The glucose disappearance rate (K) improved after the second infusion from 2.04 ± 0.23 to 2.87 ±0.16 (p < 0.001).

Serum immunoreactive insulin levels rose promptly after the glucose infusions, but while a decrease was noted following the first peak, the levels remained persistently elevated after the second glucose load. Growth hormone levels decreased and were slightly lower yet six to nine minutes after completion of the infusions.

A striking reduction of free fatty acid levels followed the first glucose load; values fell to 50 per cent of the fasting levels prior to, and decreased even further following, the second infusion. Thus, the improved K of the second glucose tolerance test was associated with already diminished serum free fatty acid levels.
A Double-blind Controlled Trial of Clofibrate in the Treatment of Diabetic Retinopathy
Authors: Harrold B P , Marmion V J , Gough K R
Published: December 2014

A double blind controlled trial has been made of clofibrate in the treatment of diabetic retinopathy. Fifty-six patients completed one year in the trial and form the basis for this paper. At the end of one year there was a significant reduction in the area of retina involved by hard exudation in the treated group. There were no significant effects on other retinal lesions. The improvement in retinal exudates was not associated with any significant improvement in visual acuity.
Influence of Physiologic Fluctuations in Plasma Growth Hormone on Glucose Tolerance
Authors: Yalow Rosalyn S , Goldsmith Stanley J , Berson Solomon A
Published: December 2014

In oral glucose tolerance tests (GTT) performed three, four, or six hours after a previous GTT, six hours after a combined protein-glucose tolerance test or two and onehalf hours after intravenous insulin, impairment in tolerance could be closely correlated with the magnitude of the growth hormone secretory response in the previous procedure. These observations support the physiologic role of growth hormone in determining glucose tolerance.

Impairment in glucose tolerance was generally associated with an augmented integrated plasma insulin response and improvement in glucose tolerance was frequently seen in association with a lesser plasma insulin response. These observations support the view that plasma insulin follows blood glucose but that the rate of glucose disposal is determined by factors other than the level of plasma insulin alone.
Femoral and Popliteal Occlusive Vascular Disease: A Report on 143 Diabetic Patients
Authors: Guggenheim Wolf , Koch Gert , Adams Andrew P , Hoar Carl S , Wheelock Frank C
Published: December 2014

A five-year review of 143 diabetic patients with circulatory insufficiency of the lower extremity established: (1) The distal superficial femoral and the popliteal arteries demonstrated the greatest number of occlusions, whereas the collaterally important profunda femoris was found consistently patent. (2) Absence of pulses below the femorals carried insufficient quantitative prediction of radiographic collateral, or run off patterns. (3) Collaterals and major arterial run off below the knee were of equal prognostic value, the adequacy of either resulting in successful surgery twice more often than with poor or absent collaterals, respectively run off.
Experimental Diabetic Microangiopathy: 1. Basement Membrane Statistics in the Dog
Authors: Bloodworth J M B , Engerman R L , Powers K L
Published: December 2014

The capillary basement membrane width in the kidney, retina, muscle and fat of ten diabetic dogs is reported. Five of the dogs were made diabetic by bovine pituitary growth hormone and five by alloxan. The results show that a statistically valid increase in basement membrane width in capillaries of kidney, retina and muscle is produced by the diabetic state. Fat capillaries, however, show no effect of the diabetic state.
Studies on the Ability of Compounds to Block the Diabetogenic Activity of Streptozotocin
Authors: Dulin William E , Wyse Beatrice M
Published: December 2014

Evidence is presented that the early hyperglycemia (two to four hours after injection) following streptozotocin administration is not a result of an interference with insulin action, since streptozotocin did not block insulin action on skeletal muscle in vitro.

Compounds with known metabolic effects were tested for their ability to block streptozotocin-induced diabetes. Mannoheptulose, glucosamine, diazoxide, NAD, glucose, epinephrine, 3,5-dimethylpyrazole, 3-carboxy-5-methylpyrazole, glutamic acid, glycine, asparagine, cysteine, sodium tolbutamide, guanidoacetic acid, glutathione, p-aminobenzoic acid, and ethyl alcohol were ineffective as blocking agents. Pretreatment with pyrazinamid blocked streptozotocin diabetes,but was ineffective following streptozotocin treatment. 2-carboxypyrazine (the metabolite of pyrazinamide) did not block streptozotocin diabetogenic activity. Administration of 2-deoxyglucose blocked streptozotocin-induced diabetes; this is postulated to be the result of an interference with streptozotocin transport into the β cell.

Pretreatment with nicotinamide, or treatment as long as two hours after streptozotocin, blocked the diabetogenic effect of streptozotocin. Nicotinic acid was ineffective. It is postulated that streptozotocin interferes with NAD formation in the β cell, and that nicotinamide treatment abolishes the streptozotocin effect by its ability to maintain ah adequate concentration of NAD in the β cell.
Congenital Anomalies and Diabetes in the Pima Indians of Arizona
Authors: Comess L J , Bennett P H , Burch T A , Miller Max
Published: December 2014

Medical records of 1,207 Pima Indian children were examined for reported congenital anomalies. Anomalies occurred in eight (38.1 per cent) of twenty-one offspring born after the onset of diabetes to mothers whose disease was diagnosed before age twenty-five, but in only 3.7 per cent of the offspring of all other women. Children born after the onset of diabetes to mothers whose disease started at or after age twenty-five, and those born to prediabetic mothers had anomalies no more frequently than the children of nondiabetic mothers. Congenital anomalies were not related to paternal diabetes. Anomalies were more frequent in children from “diabetic” pregnancies during which the mother required hypoglycemic medication than from those during which medication was not required. Although a genetic mechanism cannot be completely excluded, the data better support the hypothesis that diabetes produced fetal anomalies among the Pima Indians by its influence upon the intrauterine environment during early pregnancy.
Effect of Intravenous Tolbutamide on Serum Insulin Levels in Pancreatic Diabetes
Authors: Joffe B I , Bank S , Jackson W P U , Vinik A I , Keller P
Published: December 2014

Intravenous tolbutamide was administered to seven patients with diabetes secondary to chronic calcific pancreatitis who had not previously received insulin. A matched group of normal controls was similarly investigated. The pancreatic diabetic patients were found to respond to tolbutamide with a significantly impaired serum insulin rise compared to the control group, while their fall in plasma glucose was delayed and significantly less pronounced. The relationship between insulin responses in pancreatic and in primary diabetes is briefly discussed and therapeutic implications of the findings are considered.
Streptozotocin Diabetes in the Mouse and Guinea Pig
Authors: Brosky G , Logothetopoulos J
Published: December 2014

A single injection of streptozotocin into mice produced an extensive necrosis of the beta cells resulting in permanent diabetes. The histological changes in the islets were similar to those described after the injection of alloxan. The regenerative capacity of beta cells which survived the cytotoxic injury was limited.

Hypoglycemia induced by an injection of insulin or hyperglycemia induced by glucose injections sensitized the beta cells to streptozotocin. In contrast, injection of insulin antibody effectively protected the beta cells from the cytotoxic injury.

Streptozotocin caused widespread necrosis of the beta cells of the guinea pig and the obese hyperglycemic mouse. Both these species had proven resistant to the diabetogenic effect of alloxan.

Diabetic guinea pigs were observed for eight months, without reversion of the diabetic syndrome.
Effect of Cold (4° C.) on Catecholamine Excretion in the Diabetic Rat and Its Relation to Autonomic Neuropathy
Authors: Nathanielsz P W
Published: December 2014

Total urinary catecholamine excretion has been estimated in rats made diabetic with alloxan. The mean value for diabetic rats was 1.4 μg./100 gm. in twenty-one hours at 20° C. Nondiabetic controls from the same litter excreted 0.8 μg./100 gm. Exposure to 4°C. for the first five hours of this period increased the excretion in the diabetic rats by 74 per cent to 2.4 μg./100 gm. and 82 per cent in the controls to 1.5 μg./100 gm.