bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin-like Activity by Fat Pad Assay and Immunoreactive Insulin: I. Their Correlation in Native Serum, Acid-ethanol Extract and Salt-ethanol Extract
Authors: Ide Takehiko , Kuzuya Takeshi , Kajinuma Hiroshi , Kanazawa Yasunori , Kosaka Kinori
Published: December 2014

In view of controversies on the relationship of ILA (insulin-like activity) and IRI (immunoreactive insulin) in blood, removal of extra factors other than insulin was attempted by means of salt-ethanol (acid-ethanol-NaCl) or acid-ethanol extraction methods prior to assay. The saltethanol procedure, a modification of Romans' method for the extraction of pancreatic insulin, proved to be more efficient in extraction. ILA was assayed by rat fat pad method using C-14-O2 production from glucose-U-C-14 as index. IRI was assayed by a double antibody radioimmunoassay. Dog sera obtained from the pancreatic and femoral veins were chiefly used. Recoveries of endogenous IRI by saltethanol and acid-ethanol methods were 90 per cent and 72 per cent respectively, which were almost identical with recoveries of I-131-insulin added to sera. The ILA of the extracts differed considerably from the ILA of the original sera; the recovery scattered widely beween 5 and 116 per cent. In contrast to wide discrepancies between ILA and IRI in the native sera, ILA and IRI in the extracts were much closer to each other. There was a good parallelism between regression lines of ILA in the extracts and of standard insulin, but deviation was significant between the regression lines of insulin and untreated sera. The ILA in the extracts of dog and human serum was mostly suppressed with antiinsulin serum. Thus, endogenous IRI behaves like pancreatic insulin during extraction procedure and appears to possess biological activity corresponding to its immunoreactivity.
An Insulin Dependent Effect of Chronic Tolbutamide Administration on the Skeletal Muscle Carbohydrate Transport System
Authors: Feldman Jerome M , Lebovitz Harold E
Published: December 2014

With the use of an in vitro intact mouse diaphragm preparation, the effects of tolbutamide on the sugar transport system of skeletal muscle as measured by 2 deoxyglucosc uptake (2-DG) was studied. Tolbutamide alone was found to have no effect on in vitro 2-DG uptake. Insulin mediated 2-DG uptake in vitro was not consistently changed by the addition of tolbutamide to the system. However, diaphragms from either subacute (24 hrs.) or chronically (eight to twelve days) tolbutamide treated animals showed a consistent increase in insulin mediated 2-DG uptake as compared to the appropriate controls. It was necessary to have tolbutamide in the preincubation and incubation medium in order to demonstrate this effect on the diaphragms of tolbutamide treated animals. This in vitro potentiation of insulin mediated 2-DG uptake occurred with physiologic concentrations of insulin (26 μU.'ml.) and normal therapeutic levels of tolbutamide (0.2 mg./ml.). The data suggest that potentiation of insulin action on the skeletal muscle sugar transport system maybe one of the major effects of tolbutamide therapy.
Pancreatic B Cell Morphology and Insulin Content of Normal and Alloxan-Diabetic Rabbits and Their Offspring
Authors: Wellmann Klaus F , Volk Bruno W , Lazarus Sydney S , Brancato Paul
Published: December 2014

The pancreases of eight normoglycemic and of nine alloxan-diabetic rabbits, and those of their respective litters, sacrificed within one week after birth, were studied by light and electron microscopy and were assayed for insulin by the double-antibody method. The insulin concentrations of the pancreases from the neonatal rabbits averaged 0.56 U. per gram of wet tissue in rabbits born to normoglycemic mothers and 0.73 U. in those born to alloxan-diabetic animals. Since ultrastructurally in the neonatal rabbits of both groups mostly paid B cell granules were encountered, it is concluded that pale granules contain assayable insulin. This agrees with previous immunofluorescent studies, in which it was also shown that the pale granules contain insulin. The relatively lower number of B cell granules as well as the more prominent display of vesicular units of the endoplasmic reticulum in rabbits born to alloxan-diabetic animals suggest that a state of hyperfunction, induced by hyperglyceinia transmitted through the placenta by the mother rabbit, exists in the B cells of this group of neoaates. On the other hand, the absence of blood sugar changes in the diabetic mother animals during pregnancy is in keeping with former observations that insulin fails to cross the placental barrier in rabbits (and other mammals).
Relationship of Glucose Tolerance to Hepatic Glucokinase Activity
Authors: Hornichter Richard D , Brown Josiah
Published: December 2014

Glucokinase, a glucose phosphorylating enzyme found only in liver, has been shown to be both glucose and insulin dependent, as well as glucose specific. Since the liver is freely permeable to glucose, phosphorylation of glucose to glucose-6-phosphate is a potentially rate-limiting step in hepatic glucose utilization and thus an important factor in the determination of oral glucose tolerance. Rats lube fed 0.5 gm. glucose/100 gm. body weight, as the glucose tolerance test, were studied under varying dietary conditions to discover if a correlation between glucokinase activity and glucose tolerance is present. In general, such a relationship was found to exist. Following starvation and following sucrose refeeding, hepatic glucokinase activity was quite low and glucose tolerance curves were significantly elevated when compared to Purina Chow fed rats or glucose refed rats. The glucose refed rats had high hepatic activities of glucokinase when compared with all other groups, and glucose was rapidly cleared from the blood. Fructose refed rats had low levels of hepatic glucokinase activity but did not show glucose intolerance. The explanation for this latter finding remains obscure but several possibilities are discussed.
Pancreatic Insulin Content of Nonpregnant, Pregnant and Postpartum Rats and the Developing Rat Fetus
Authors: Rishi Surendra , Golob Erich K , Becker Kenneth L , Shah Narendra
Published: December 2014

A study was made of the insulin content of pancreases of nonpregnant, pregnant and postpartum rats and of their developing fetuses. The insulin content of the extracts was measured by radioimmunoassay, using crystalline rat insulin as a standard. The mean concentration of insulin in the pancreas of nonpregnant animals was 43 ± 6 μg./gm. The insulin concentration did not change significantly during late pregnancy or on day 4 postpartum. However, the weight of the pancreas was significantly greater in the pregnant and the postpartum rats. Thus, the total insulin content of the pancreas was greater in the pregnant and postpartum rats, being 23 ± 1.4 μg. and 24 ± 1.9 ng. respectively, as compared to 15 ± 0.7 μg. in the nonpregnant rats.

The fetal pancreases were obtained at five periods of gestation: daily from day 18 to day 22, and on day 4 after birth. The mean weight of the fetal pancreases progressively and significantly increased from 4.4 ± 0.3 mg. on day 18 to 14.1 ± 1.5 mg. on day 20. On day 4 after birth, the mean pancreatic weight was 15.1 ± 0.5 mg. The fetal pancreatic insulin concentration rapidly and progressively increased from 14 ± 2 μg./gm. on day 18, to 80 ± 9 μg./gm. on day 21, and by day 4 after birth was 621 ± 103 μg./gm. By day 21 the fetal pancreatic insulin concentration had reached the prenatal peak and was already twice that of the mother. The total fetal pancreatic insulin content showed a progressive increase during the fetal life from 0.07 ± 0.01 μg. on day 18, to 1.23 μg. on day 21, a seventeen fold increase.
Immunologic and Biologic Activities of the Heterogeneous Components of Insulin
Authors: Stoll Ralph W , Ensinck John W , Williams Robert H
Published: December 2014

Four preparations of crystalline porcine insulin were fractionated into two peaks by Sephadex gel filtration in 1M acetic acid. The minor peak b was of larger molecular size than the major insulin containing peak c. Peak b was heterogeneous on polyacrylamide disc-gel electrophoresis and after limited trypsin digestion a portion migrated on the gels similar to insulin. Peak b had a high degree of cross-reactivity in a radioimmunoassay for porcine insulin. In comparison with its immunoreactivity, peak b had significantly decreased biologic activity as measured by the rat hemidiaphragm and isolated fat cell assays. The possibility that components of peak b may be present in body fluids requires re-evaluation of the biologic effectiveness of substances detected by insulin radioimmunoassay.
Determination of Urine Glucose by Measurement of Rate of Oxygen Consumption
Authors: Kadish Arnold H , Sternberg James C
Published: December 2014

The glucose level of plasma, serum, urine and other bodily fluids is conveniently determined by oxidation catalyzed by glucose oxidase employing a polarographic oxygen sensor with a circuit modified to measure the rate of oxygen consumption. Data obtained from a population of 789 urine samples collected from normal subjects of both sexes and all ages are presented. From the data, it appears that the renal threshold for glucose is dependent upon the threshold of the analytic method employed. Urinary interferences associated with prior glucose oxidase methods are circumvented by measuring oxygen consumption instead of peroxide formation.
Size of the Gallbladder in Patients with Diabetes Mellitus
Authors: Gitelson S , Oppenheim D , Schwartz A
Published: December 2014

The surface of the X-ray shadow of the gallbladder was determined by a planimeter in 100 random patients examined for complaints suggesting gallbladder disease, in whom the viscus was well visualized and no gallstones were discernible. No correlation was found between the gallbladder size and body surface or sex.

The mean surface of the gallbladder shadow in thirty-two diabetic patients was significantly larger than the mean surface in forty-three nondiabetic individuals. The frequency of large gallbladders (over 24 sq. cm.) was higher among the diabetic than the nondiabetic individuals.

Elimination of twenty-seven diabetic and nondiabetic patients with clinical signs of cholecystitis, duodenal ulcer or gastroduodenitis did not alter the relationship between the gallbladder size and presence of diabetes, found for the whole group.

In some diabetic patients the large gallbladder may be a manifestation of biliary dyskinesia due to autonomic neuropathy (“diabetic neurogenie gallbladder”). A search for diabetes is justified in patients with a large gallbladder.
Lipid Class and Fatty Acid Composition of Rat Brain and Sciatic Nerve in Alloxan Diabetes
Authors: Pratt J Howard , Berry James F , Kaye Beverly , Goetz Frederick C
Published: December 2014

Quantitative analysis of major lipid classes and the fatty acids carried out on lipid extracts of brain from young and adult alloxan diabetic rats revealed decreases in total lipid, cholesterol, the more polar cerebroside, and phospha-tidylethanolamine in brain from young diabetic rats. No significant changes in lipid class composition were found in brains from adult rats with alloxan diabetes. No significant changes in fatty acids were detected in the total brain lipids of young or adult rats as a result of alloxan diabetes. In contrast, similar studies on the lipids of sciatic nerve revealed an increase in cholesterol balanced by a decrease of triglycerides in young rats and a decrease of total lipid and the more polar cerebroside only in adult rats with alloxan diabetes. Compared to normal rats, total lipids from sciatic nerves of young alloxan diabetic rats showed relative decreases in palmitate (16:0), oleate (18:1), and linoleate (18:2) with increases in stearate (18:0), eicosanoate (20:0), eicosenoate (20:1), arachidonate (20:4), docosanoate (22:0), docosapentaenoate (22:5), docosahexaenoate (22:6), lignocerate (24:0). In lipid extracts from sciatic nerves of adult diabetic rats, only oleate (18:1) was increased and linoleate (18:2) decreased compared to normal.
Post-Heparin Lipolytic Activity in Diabetic Patients with a History of Mixed Hyperlipemia: Relative Rates Against Artificial Substrates and Human Chylomicrons
Authors: Wilson Dana E , Schreibman Paul H , Arky Ronald A
Published: December 2014

The mechanism responsible for the accumulation of chylomicrons in mixed hyperlipoproteinemia (Type 5) is not known. Assays of the plasma-clearing factor, lipoprotein lipase, with artificially prepared substrates have been normal or only mildly depressed in this condition. The recent report of a patient in whom there was marked depression of activity against native chylomicrons despite normal activity against an artificial substrate suggested, however, that there might exist a qualitative defect in the function of lipoprotein lipase undisclosed by assays with the artificial substrate in general use. Accordingly, the lipolytic activity of post-heparin plasma from five diabetic patients with mixed hyperlipoproteinemia was measured against two artificial substrates and two preparations of human chylomicrons. There was good correlation between activity against coconut oil and each of the three other substrates over a wide range of plasma glyceride concentrations and post-heparin lipolytic activities. The data support the conclusion that plasma post-heparin lipolytic activity in diabetic patients with mixed hyperlipoproteinemia is qualitatively normal.
Estimation of Vascular Basement Membrane Thickness: Theoretical and Practical Considerations
Authors: Williamson Joseph R , Vogler Nancy J , Kilo Charles
Published: December 2014

The major sources of error and variation in estimates of basement membrane thickness (BMT) are attributable to variations in conditions of specimen preparation, errors in magnification, and sectioning artifacts related to variation in section thickness and tangential sectioning.

A simplified method for estimating BMT, requiring only two measurements per vessel, is described and justified theoretically from analysis of a model system. The chief merits of the method are: (1) the estimate of BMT obtained closely approximates true BMT, (2) variations in measurements related to section thickness and tangential sectioning are minimized, (3) coefficients of variation are smaller than for measurements obtained by averaging multiple measurements around the circumference of the vessel, and (4) a considerable reduction in time and effort required to obtain estimates of vascular BMT. Validation of these advantages is demonstrated in estimates of vascular BMT in a group of young adult subjects.

The importance of correcting for asymmetrical distribution of basement membrane measurements prior to statistical analysis, of eliminating inhomogeneity in control groups, and of defining the normal range of basement membrane thickness statistically is discussed.
Studies on the Secretion of Pancreatic Glucagon
Authors: Chesney Thomas McC , Schofield J G
Published: December 2014

Glucagon secretion was studied in isolated pancreatic islets, thus avoiding interference from immunologically cross-reactive polypeptides of gut origin. Glucagon release was measured by radioimmunoassay. High concentrations of glucose were shown to inhibit glucagon release. Certain amino acids and ouabain were found to stimulate glucagon release, but adrenergic agents and tolbutamide were without effect. Theophylline was found to be a potent in vitro stimulus to glucagon release, suggesting that the intracellular concentration of cyclic adenosine 3′,5′-monophosphate may play a role in the regulation of glucagon secretion.
Hyperglycemic Response to Massive Doses of Commercial Insulin
Authors: Glasgow Allen M
Published: December 2014

Commercial insulin in massive doses produces an initial hyperglycemic when given to normal rabbits. Large doses, 15 U./kg., of commercial insulin produce a higher plasma glucose than a smaller dose, 2 U./kg., of the same insulin during a period of thirty minutes following the injection. The initial hyperglycemia and the delay of hypoglycemia appear to be due to glucagon in commercial insulin preparations. As little as 0.1 per cent by weight of glucagon will produce this effect. With multiple injections of large doses of insulin every thirty minutes, an evaluation of plasma glucose is seen after each injection and hypoglycemia can be greatly delayed. A qualitatively similar response is also seen in alloxan diabetic rabbits. It is felt that the hyperglycemic effect might be of importance in the treatment of insulin resistance and might explain some cases of acute insulin resistance.
Studies on the Site and Mechanism of Action of Phenformin: I. Evidence for Significant “Nonperipheral” Effects of Phenformin on Glucose Metabolism in Normal Subjects
Authors: Hollobaugh Samuel L , Rao M Bhaskar , Kruger Fred A
Published: December 2014

Oral and intravenous glucose tolerance tests were performed in ten normal subjects. Phenformin pretreatment flattened the glucose and insulin response to oral glucose loading but did not significantly alter the response to intravenous glucose. It is suggested that these results can best be explained by an inhibitory effect of the drug on the rate of intestinal glucose absorption.
Hyperglycemia and Hyperosmolarity in a Brittle Diabetic with Thyrotoxicosis
Authors: Jacobson R , Horenstein M , Kassel L
Published: December 2014

A thirty-six-year-old female brittle diabetic presented in a confused state complaining of intense thirst. She had a twelve-year history of known diabetes mellitus but for the previous five years had been well controlled. Four years before admission she was found to be euthyroid with a PBI of 6.8 meg. per 100 ml.

On examination she was dehydrated and without Kussmaul respirations. Blood sugar on admission was 1,590 mg./100 ml. and only a trace of acetone was detected in urine. Calculated serum osmolality was 365 milliosmols/liter. The patient responded well to 800 U. of Regular Insulin and eight liters of intravenous hypotonie solutions. However the pulse rate remained at 140/min. with no evidence of heart failure or infection; EKG showed sinus tachycardia. Evaluation of the patient's thyroid function revealed hyperthyroidism. I-131 uptake after twenty-four hours was 74 per cent. The glucocorticosteroids were found to be within normal limits.

Four months after receiving methimazole 40 mg./day the hyperthyroidism and diabetes mellitus were well controlled.
Intestinal Absorption of Sugars, Water and Sodium in Alloxan Diabetic Rats
Authors: Levinson Richard A , Englert Edwin , Smith Stanley E
Published: December 2014

Jejunal and ileal absorption of D-galactose, 3-methyl-D-glucose, D-xylose, sodium and water were studied in vivo in normal and alloxan diabetic rats. Contrary to previous studies, there was no consistent increase in sugar absorption in diabetic over normal rats. Diabetic rats absorbed significantly more sodium and water than normals, probably on the basis of diabetes-induced dehydration, but the increased sodium absorption did not stimulate increased sugar absorption. Diabetic rats, as did normal rats, showed increased jejunal over ileal sugar absorption but salt and water absorption were not different between the intestinal segments.
Platelet Phospholipids and Their Function in Patients with Juvenile Diabetes and Maturity Onset Diabetes
Authors: Nordöy Arne , Rödset J M
Published: December 2014

Platelet factor-3 activity and availability, platelet phospholipids and their fatty acid and aldehyde composition were examined in patients with juvenile diabetes of long duration and in patients with maturity onset diabetes.

Increased coagulant activity was found in platelet rich and platelet poor plasma from patients with juvenile diabetes, whereas plasma from patients with maturity onset diabetes reacted as the control group. Platelet rich plasma exposed to ADP, kaolin or freezing and thawing three times reacted not significantly differently from the controls.

Increased amount of lipid-P was present in platelets from both patient groups. In patients with juvenile diabetes the increase was mainly caused by an increase of serine phos-phoglycerides and in the other patient group all main phos-pholipid fractions were increased. The phospholipid/protein ratio of platelets was not significantly different in the three groups. Only moderate changes were observed in the fatty acid pattern of the various phospholipids.
Effect of Pituitary Ablation on Diabetic Retinopathy Studied by Fluorescence Angiography
Authors: Kohner Eva M , Dollery C T , Fraser T R , Bulpitt C J
Published: December 2014

1. Seventeen patients with diabetic retinopathy were studied before, and at various times following yttrium-90 implantation of the pituitary by means of fluorescence angiograms. 2. The studies demonstrated improvement in capillary abnormalities including microaneurysms, capillary dilatation and small areas of capillary nonperfusion following both partial and maximal pituitary ablation. 3. Study of microaneurysm turnover rates showed a significant de crease in the formation of new ones as compared with the rates of patients followed as controls to the pituitary implanted ones. Disappearance of existing microaneurysms was also accelerated, but this did not reach statistical significance. 4. Abnormalities in small (20–50 μ) arteries improved, while large arterial disease continued in spite of pituitary ablation. 5. New vessels often regressed but they only disappeared completely if the ablation was complete. 6. No retina returned to complete normality following pituitary ablation. 7. The most marked effect of pituitary ablation was the slowing down of the rate of formation of new microvascular lesions.
Blood Sugar, Serum Insulin and Free Fatty Acid Interrelationships During Intravenous Tolbutamide Testing in Normal Young Adults and in Patients with Insulinoma
Authors: Grunt Jerome A , Pallotta Johanna A , Soeldner J Stuart
Published: December 2014

Blood sugar, serum immunoreactive insulin and free fatty acids were determined in three young male patients with islet cell tumors and in thirty young adult controls before and after intravenous injection of tolbutamide. The serum insulin response was compatible with the diagnosis in two of the patients who had high fasting insulin levels, but was of no value in the one patient with normal fasting insulin concentrations. Evaluation of the fasting blood sugar and free fatty acid concentrations in relation to the fasting insulin levels (FBS/IRI and FFA/IRI) made the diagnosis more apparent in all three insulinoma patients. The FBS/ IRI for the thirty male controls was 5.6 ± 1.2 (mean ± 2 S.E.M.). Only three of these values were below 2.5. In contrast, not one of the thirty-four preoperative FBS/IRI values from the three patients was above 2.5. All seventeen postoperative FBS/IRI values were above 2.5. The FFA/IRI for the thirty male controls was 30.6 ± 9.4. Only four of these values were below 15. In the two patients where data were available, twelve of the fourteen values were below 15.
Diabetogenic Action of Alloxan Following Temporary Interruption of Arterial Blood Flow to Pancreas in Rats
Authors: Bilic N , Felber J-P
Published: December 2014

Ligation of the superior mesenteric and the superior pancreatico-duodenal arteries just prior to alloxan treatment and their release ten minutes after treatment did not protect rats against development of alloxan diabetes. Prior incubation of alloxan in vitro for a period of ten minutes at a physiological pH value and 37° C. resulted in loss of diabetogenic activity. Identical blood flow interruption without alloxan treatment did not produce elevated blood glucose levels.

After the intravenous injection of alloxan, a substance giving a fluorescence product with alloxan reagent was detected in blood over four hours. The substance remained at higher levels when animals, prior to alloxan treatment, were injected with reduced glutathione. There was also a prolonged detection of alloxan during incubation in whole blood and in buffer containing reduced glutathione. The production of alloxan diabetes following temporary interruption of arterial blood flow is discussed in the light of the present results.
Urinary Excretion of Insulin A Chain by Normal and Diabetic Subjects
Authors: Varandani P T , Crevensten Patsy , Nafz Mary Ann
Published: December 2014

With the use of a radioimmunoassay procedure it has been found that the A chain of insulin is a normal constituent of human urine. Only about 0.2 per cent of the plasma A chain is “cleared” in urine. The A chain excreted per mg. creatinine was significantly higher in the case of diabetic than that of normal subjects.
Steroid Diabetes in the Guinea Pig: Studies on Islet-cell Ultrastructure and Regeneration
Authors: Kern H , Logothetopoulos J
Published: December 2014

Guinea pigs were maintained hyperglycemic and glucosuric by daily subcutaneous injections of prednisolone suspension. The stimulated beta cells showed de granulation, increased density of rough endoplasmic reticulum and expanded elaborate Golgi complexes. Glycogen particles accumulated progressively in these cells until by the third month glycogen aggregates encroached on large areas of the cytoplasm. By the fourth and fifth month many beta cells appeared as small bags filled with glycogen. Cytoplasmic remnants in these glyco gen-filled beta cells showed organelles of normal appearance. Beta cells proliferated during the first two months as evaluated by the proportion of beta cells incorporating 3H-thymidine. In guinea pigs killed after threeand four months of prednisolone treatment the 3H-thymidine index declined to levels found in untreated guinea pigs.
Lower Extremity Amputation in Diabetic Patients
Authors: Ecker Malcolm L , Jacobs Bernard S
Published: December 2014

One hundred and seventy-eight lower extremity amputations performed on 103 diabetic patients were reviewed. Although the healing rate for the above-the-knee amputation was higher, the probability of prosthetic use and ambulation was greater with the mid-leg amputation, particularly if the patient required bilateral amputation. Late breakdown of the mid-leg stump, once healing had occurred, was not a significant problem. We feel that the proper amputation level is bestdetermined by the skin temperature and appearance at the proposed amputation site rather than rigid reliance on the presence of pulses, oscillometry, or arteriography and that every effort should be directed to retaining a functioning knee.
A Long-Term Effect of Insulin on Collagen Synthesis by Newborn Rat Bone in Vitro
Authors: Schwartz P L , Wettenhall R E H , Troedel M A , Bornstein J
Published: December 2014

In order to further characterize the effects of insulin on collagen synthesis by newborn rat bone in vitro, the time course of insulin action on incorporation of proline as proline and as hydroxyproline has been studied. In an incubation system, there was no stimulation by insulin at either three or six hours. In a flowing organ culture system, no significant effect of insulin could be observed at six hours; a small but significant effect on incorporation of proline as proline (but not as hydroxyproline) was seen at eighteen hours; and a highly significant effect on the incorporation of proline as both proline and hydroxyproline was observed at forty-two hours. Possible explanations for the delayed onset of insulin activity are discussed and the pattern contrasted with the rapid effect of insulin on collagen synthesis by skin of newborn rats.
Relationship Between Body Composition and Insulin and Growth Hormone Responses in Obese Adolescents
Authors: Schultz Robert B , Parra Adalberto
Published: December 2014

The clinical characteristics and predicted body composition of ten obese nondiabetic and six normal adolescents were compared in regard to plasma insulin, growth hormone, glucose, free fatty acids and alpha-amino nitrogen in response to different stimuli. Analysis of the data suggested the presence of two groups of patients. In obese Group A there was no family history of obesity, the youngsters first became obese between seven to twelve years of age, had a normal height for age, moderate increase in body weight and estimated total body fat, and normal or less than normal fasting levels of insulin. In obese Group B there was a strongly positive family history of obesity, the subjects became obese in infancy or early childhood, they were tall for their age, had marked increase in total body weight and total body fat as well as significantly higher than normal fasting insulin levels. Hyperinsulinemia was present in Group A during the oral glucose tolerance test and protein glucose meal. Normal insulin responses were observed during the protein meal and the arginine tolerance test. On the other hand, Group B manifested hyperinsulinemia in response to all stimuli. Both obese groups had undetectable plasma growth hormone levels during both the protein and the protein-glucose meal, but normal growth hormone responses during the oral glucose and the arginine tolerance tests. The differences in plasma levels of glucose and free fatty acids were minimal. Significant differences in plasma alpha-amino nitrogen values were observed during the protein-glucose meal. Differences in the hormonal responses of obese adolescents and adults are discussed. Possible explanations for heterogeneous responses of obese adolescents are presented.
Utility of Equivocal Glucose Tolerances
Authors: Danowski T S , Aarons J H , Hydovitz J D , Wingert J P
Published: December 2014

Interpretation of the results of an oral glucose tolerance test is simplified when the results are expressed as the Glucose Tolerance Sum for two or for three hours (GTS0-2 hr and GTS0-3 hr.).

The GTS0-2 hr value is the sum of the 0, ½, 1 and 2-hr, glucose levels in venous blood when 1.75 gm. of glucose are administered per kilogram of body weight. Data from more than 1,100 such tolerances indicate that when GTS0-2 hr is 500 or less there is a 98 to 100 per cent probability that the test is clearly normal by the standards of the World Health Organization, British Diabetic Association, United States Public Health Service, and Fajans and Conn of what is and what is not diabetes mellitus. On the other hand, when the GTS0-2 hr is 801 or higher the test would meet each of the four sets of above cited criteria for diabetes. Since those values between 501 and 800 are variably classifiable as normal or abnormal by these same four standards, this represents the equivocal zone.

The GTS0-3 hr value is based on the sum of 0, 1, 2, and 3-hr, blood glucose levels in the above tolerance tests. Using the same criteria, clearly nondiabetic tolerance tests yield GTS0-3 hr values of 450 or less, while those deemed to be diabetic have sums of 701 or higher. Intervening GTS0-3 hr values of 451 to 700 represent the equivocal zone.

Tolerance tests with GTS values in the equivocal zone should be repeated at intervals of months or years. In our experience equivocal tests generally move toward or into the abnormal range, a minority move back into the normal zone, and some remain equivocal.
Proinsulin in B Cells of Bovine Islets Demonstrated by Fluorescein or Peroxidase-Labeled Specific Antibody
Authors: Logothetopoulos J , Yip C C , Coburn M E
Published: December 2014

Sera of guinea pigs immunized with crude bovine proinsulin, and adsorbed with a solid Sephadex-insulin immunosorbent, yielded highly specific antibodies against proinsulin.

Positive immunoreaction was obtained in the β cells of fetal and adult bovine islets with the specific antiproinsulin antibody preparations in the Coons' direct and indirect method with fluorescein- or peroxidase-labeled antibodies. It is concluded that proinsulin and/or other antigens bearing the same antigenic determinants as proinsulin are present in the β cells.
Comparative Immunology of Bovine, Porcine and Human Proinsulins and C-peptides
Authors: Rubenstein Arthur H , Welbourne W Porter , Mako Mary , Melani Franco , Steiner Donald F
Published: December 2014

The immunological cross reactions of human, porcine and bovine proinsulins and C-peptides are described. In order to iodinate the C-peptides to high specific activity, tyrosine was coupled to the molecule using N-carboxytyrosyl anhydride. The tyrosylated bovine I-131-C-peptide was bound by bovine proinsulin antisera, but did not react with porcine proinsulin or insulin antisera, while the tyrosylated human-I-131-C-peptide did not react with high concentrations of these three antisera.

The cross reaction of human and porcine proinsulin with bovine proinsulin antisera was weak and resembled that of insulins of all three species. Similar results were observed with a porcine proinsulin antiserum. Removal of the insulin-binding antibodies from a proinsulin antiserumeliminated its reactivity with heterologous proinsulins.Using an assay system (bovine proinsulin antiserum: tyrosylated-I-131-C-peptide) which did not respond to insulin, human and porcine C-peptides reacted approximately 250 and 750 times less efficiently than the bovine molecule. These results indicate that the relatively large degree of variability in the amino acid sequence of the proinsulinconnecting segments gives rise to unique immunological determinants in the three species of proinsulin studied.
Study of the Relationship Between Plasma Insulin Concentration and Efficiency of Glucose Uptake in Normal and Mildly Diabetic Subjects
Authors: Reaven Gerald M , Silvers Abraham , Farquhar John W
Published: December 2014

Removal of glucose-U-C-14 from plasma was studied in normal subjects and in patients with maturity-onset diabetes mellitus. All measurements were made after an overnight fast, during a period in which plasma glucose and immunoreactive insulin concentrations were not changing. The mean irreversible loss rate (ILR) of glucose from the plasma of normal subjects was not different from that of patients with diabetes: mean ILR (± the coefficient of variation) of all patients was 1.36 (± 14 per cent) mg. glucose/kg, body weight per min. This narrow range attests to the similarity of ILR in the patients studied. There was no correlation between glucose ILR and plasma glucose concentration, plasma immunoreactive insulin concentration, or ponderal index. In contrast, fractional glucose irreversible loss rate varied considerably from patient to patient, with a coefficient of variation of 35 per cent. Furthermore, there was a strong negative correlation between plasma glucose concentration and fractional glucose irreversible loss rate (r = −0.82, p < .01). This decrease in efficiency of glucose removal from plasma of hyperglycemic patients was not related to an absolute lack of insulin. It is concluded that net glucose utilization in the fasting state is similar in normal and mildly diabetic patients, and that fasting hyperglycemia is due to a decrease in efficiency of glucose removal which cannot be attributed to absolute insulin deficiency.
Preliminary Clinical Evaluation of Glybenclamide in Treatment of Diabetes Mellitus
Authors: Johnson B F , Bhatia C K , Rzeszotarski W J , Wolff F W
Published: December 2014

An initial clinical trial with a new hypoglycemic sulfonylurea is described. In most patients, significant reductions in blood sugar and elevations of plasma insulin levels were produced throughout the day, by doses ranging from 2.5 to 15 mg. twice daily. The greatly enhanced activity compared to other sulfonylureas may be due to increased hydrophobic bonding to the receptor vicinity. Two patients developed hypoglycemic reactions. Transient elevations in transaminase levels were the only other toxic effect noted. Our results to date do not suggest that this compound is clinically advantageous to other orally active hypoglycemic agents.
Aortic Mucopolysaccharides in Experimental Diabetes
Authors: Cohen Margo P , Foglia Virgilio G
Published: December 2014

The effect of experimental diabetes, produced by 95 per cent pancreatectomy, on the synthesis and concentration of specific mucopolysaccharide fractions in rat aortas was studied. Animals were sacrificed three and six months after pancreatectomy, and the findings were significantly different at the different times. It was found that at three months, when blood sugar levels were only minimally elevated, the concentrations of chondroitin-4-sulfate, chondroitin-6-sulfate and dermatan sulfate-containing fractions were markedly increased, whereas six months after panereatectomy the concentrations of the chondroitin-4-sulfate and chondroitin-6-sulfate-containing fractions were lower than normal. The increase in these fractions at three months is ascribed to both increased synthesis and decreased degradation. At six months, concomitant with the rise in blood sugar, the metabolic pattern was reversed and there was decreased synthesis and increased degradation of these substances.
Mean Amplitude of Glycemic Excursions, a Measure of Diabetic Instability
Authors: Service F John , Molnar George D , Rosevear John W , Ackerman Eugene , Gatewood Lael C , Taylor William F
Published: December 2014

Three normal, three stable diabetic, and eight unstable diabetic subjects were investigated, with continuous automated blood glucose analysis for forty-eight-hour periods, during metabolic balance studies of six days' duration under near normal conditions (fed and ambulatory) after the attainment of clinically optimal diabetic regulation. The studies on unstable diabetics were performed during constant dietary intake, with one or two daily injections of intermediate-acting insulin and then repeated with four daily injections of short-acting insulin. A characteristic of blood glucose behavior, the mean amplitude of glycemic excursion (MAGE), was measured. MAGE was small for normals (range, 22 to 60 mg./100 ml.), larger for stable diabetics (67 to 82 mg./100 ml.), and largest for unstable diabetics (119 to 200 mg./100 ml.). Associated with a significant decrease (p = 0.004) in the mean diurnal glycemic level (from 146 to 244 mg,/100 ml. to 101 to 152 mg./100 ml.) achieved through the use of four daily doses of short-acting insulin there was a significant increase (p = 0.006) in hypoglycemic episodes (from 0 to 4/48 hr. to 3 to 6/48 hr.) without significant change in MAGE. The persistently large value of MAGE despite therapy with multiple injections of short-acting insulin appears to be a characteristic of unstable diabetes.
Insulin Immunoassay by Back-Titration; Some Characteristics of the Technic and the Insulin Precipitant Action of Alcohol
Authors: Wright Peter H , Makulu David R , Vichick Diana , Sussman Karl E
Published: December 2014

Precipitation of insulin by alcohol and some aspects of the “back-titration” method of insulin immunoassay were investigated. In the absence of insulin antibodies, alcohol has a definite nonspecific precipitant action on labeled insulin, an action which is most marked when alcohol is added in high concentration or when the medium contains much protein. This nonspecific precipitation of radio-iodinated insulin is not affected by the presence of high concentrations of unlabeled insulin; this is not explained but has no effect upon the assay system. The “back-titration” method of insulin assay is more sensitive and reproducible than the “competitive” technic when the latter is carried out under similar brief conditions of incubation. The “back-titration” method is shown to be specific for insulin, proinsulin being the only other hormonal substance tested and found to interfere with the assay system. The assay is not affected by small changes in pH about neutrality, can be carried out with pooled anti-porcine or anti-bovine insulin serum, and is not species-specific. Results obtained with human plasma are comparable with those found by the method of Morgan and Lazarow. Expected amounts of insulin are recovered over a wide range of plasma dilutions. For routine purposes, illustrated in a series of glucose tolerance tests, the “backtitration” method has proved practical, rapid, and reproducible.
Effect of Experimental Diabetes Mellitus on Kidney Ribosomal Protein Synthesis
Authors: Peterson Daniel T , Greene Warner C , Reaven Gerald M
Published: December 2014

Rats were made diabetic by the administration of alloxan, streptozotocin or anti-insulin serum, and the capacity of kidney ribosome preparations to incorporate labeled amino acid into protein in vitro was compared for diabetic and normal rats. Kidney ribosomes from diabetic rats always incorporated markedly more amino acid into protein than normal controls. These results are in contrast to the decrease in hepatic and muscle ribosomal protein synthesis that has previously been shown to accompany experimental diabetes in the rat. When polysomes were preincubated to “strip off” endogenous messenger RNA, and artificial messenger was added, the increased protein synthetic activity of diabetic ribosomes persisted. Consequently, it is concluded that the effect of insulin deficiency to increase the incorporation of amino acid into protein by kidney ribosomes is most likely due to a post-transcriptional change in protein synthesis.
Portal and Peripheral Vein Immunoreactive Insulin Concentrations Following Tolbutamide Administration
Authors: Blackard William G , Nelson Norman C
Published: December 2014

The effect of tolbutamide on portal and peripheral vein immunoreactive insulin concentrations in man was assessed and compared with that of a glucose stimulus. The portal vein IRI responses to both stimuli were similar. The ratios of peripheral vein to portal vein insulin response (area under the curve) following tolbutamide administration were the same or lower than that following a glucose infusion.
Enhancement of Arginine-induced Insulin Secretion in Man by Prior Administration of Glucose
Authors: Levin Seymour R , Karam John H , Hane Satoshi , Grodsky Gerold M , Forsham Peter H
Published: December 2014

Various sequential combinations of 20 gm. of glucose and 20 gm. of arginine were given as separate, twenty-minute infusions with a thirty-minute rest interval between infusions, to six nonobese, nondiabetic subjects. The sequence of glucose preceding arginine significantly enhanced the serum immunoreactive insulin response to this amino acid. Other sequences of glucose and arginine did not result in enhancement. The effect of a separate infusion of glucose preceding arginine was quantitatively similar to enhancement of insulin secretion by glucose (20 gm.) and arginine (20 gm.) infused simultaneously over twenty minutes. The response to arginine after glucose, however, resulted in earlier peak insulin levels than did the simultaneous glucose-arginine infusion.

These results imply a difference in the insulin-releasing mechanisms of arginine and glucose. It is suggested that certain time-dependent reactions, as well as a prior elevation of blood glucose are required for the enhancing influence of glucose on arginine-induced insulin secretion.
Leucocyte Zinc in Diabetes Mellitus
Authors: Pidduck Heather G , Keenan John P , Evans David A Price
Published: December 2014

Several investigations have shown that zinc metabolism is in some way abnormal in diabetes, the abnormality being characterized by a significant hyperzincuria. The present paper is the result of an investigation into the leucocyte zinc content in diabetes and in health. A method of leucocyte isolation using differential lysis with saponin and ammonium oxalate has been developed.

The results show that leucocyte zinc levels are not signi-cantly different in diabetics and in nondiabetics. Furthermore, in each group, leucocyte zinc levels were shown to be independent of sex, age, weight, and blood glucose. Plasma zinc and leucocyte zinc levels were shown not to be correlated. A “dilution effect” was found in that a decrease in zinc per unit leucocyte was observed with increasing total leucocyte count.
Differences Between Metabolic Responses to Fasting in Obese Diabetic and Obese Nondiabetic Subjects
Authors: Jackson R A , Moloney M , Lowy C , Wright A D , Hartog M , Pilkington T R E , Fraser T R
Published: December 2014

The metabolic response to two weeks' fasting and the influence of starvation on glucose tolerance have been studied in obese diabetic and obese nondiabetic subjects.

After an overnight fast, mean concentrations of both blood glucose and plasma triglyceride were significantly greater in the diabetics than in the nondiabetics. In neither group, however, were correlations found in any combination between circulating levels of triglyceride, glucose, insulin, free fatty acids, or the degree of obesity. During the fast, concentrations of plasma triglyceride and blood glucose fell slightly in the nondiabetics, but strikingly in the diabetics, and in the latter these reductions were highly correlated.

Glucose tolerance was impaired by starvation in the nondiabetics but considerably improved in the diabetics. In the former, the rise in both serum insulin and plasma lactate concentrations was delayed following starvation. In the latter, the most striking change was a reduction in the basal glucose concentration after fasting; a rise in lactate levels was observed prior to starvation but no elevation was detected during the post-fast glucose tolerance test, while serum insulin responses remained unchanged.

It is suggested that in some obese diabetics the development of endogenous hypertriglyceridemia is dependent on increased hepatic gluconeogenesis, and that a reduction in gluconeogenesis is the principal mechanism by which both plasma triglyceride levels are decreased, and glucose tolerance improved, in such patients following starvation. It is further suggested that both diminished β-cell responsiveness and decreased muscle glycolysis contribute to the genesis of starvation diabetes.
Diurnal Serum Growth Hormone Levels in Poorly and Well-controlled Juvenile Diabetics
Authors: Johansen K , Hansen Aa P
Published: December 2014

Serum growth hormone, free fatty acids and blood glucose have been measured half-hourly for twenty-four hours in seven male patients with juvenile diabetes. Three of the patients had newly diagnosed diabetes and the four other patients had had diabetes for six to nine years. In five of the patients the studies were made during good as well as poor control.

The serum growth hormone level was high and fluctuating in the newly diagnosed diabetics as well as in the diabetics with diabetes of some years duration when compared with the growth hormone level of nondiabetics. The three newly diagnosed diabetics had significantly lower diurnal serum growth hormone concentration during good control compared with poor control. In the two patients with diabetes for some years the diurnal serum growth hormone concentration was unaltered in one and higher in the other in good compared with poor control.
Improvement in Both Insulin Sensitivity and Release Following Diabetic Coma
Authors: Alford F P , Martin F I R , Pearson Margaret J
Published: December 2014

Serial estimations of both plasma insulin following intravenous glucose and the hypoglycemic potency of intravenous insulin were performed on two patients following hyperosmolar coma and in one after diabetic ketoacidosis.

In all, plasma insulin and insulin sensitivity were initially low and both increased markedly over several months. Concurrently the clinical control of diabetes was possible by either oral agents or diet alone.
Stimulation of Insulin Secretion in Rats by Pargyline and Mebanazine
Authors: Frohman Lawrence A
Published: December 2014

Intravenous injections of pargyline and mebanazine, both of which possess monoamine oxidase-inhibitor activity, resulted in an acute rise in plasma insulin in rats. A significant decline in plasma glucose was observed after the injection of pargyline. The hyperglycemic effect of epinephrine was not inhibited by pargyline nor was the insulinreleasing effect of pargyline blocked by epinephrine. Diazoxide completely abolished the effects of pargyline on insulin release. Simultaneous injection of glucose and pargyline resulted in an additive effect upon insulin release. Treatment of rats for five days with pargyline and mebanazine resulted in decreased plasma glucose and insulin levels associated with a reduction in food intake. The present studies suggest that the hypoglycemia associated with monoamine oxidase-inhibitor therapy is unrelated to the insulinreleasing effects.