bluuebunny/crossref_metadata_2025_split huggingface dataset:
Placental Glycogen Metabolism in Diabetes Mellitus
Authors: Gabbe Steven G , Demers Laurence M , Greep Roy O , Villee Claude A 
Published: December 2014

Carbohydrate metabolism may be markedly altered in the pregnant patient with diabetes mellitus. How such changes in maternal physiology affect the placenta, a tissue of fetal origin, has been studied by measuring glycogen synthetase, glycogen phosphorylase, and glycogen concentrations in fresh term placental tissue from eight normal women delivered vaginally, eight normal patients delivered by repeat cesarean section, and fifteen patients with diabetes mellitus. Placental weights were also determined.
Placentas of normal patients, whether delivered vaginally or by cesarean section, were extremely similar in all parameters studied. In contrast, the glycogen concentration in placentas from diabetic patients was significantly elevated (p &lt; .001) although glycogenesis appeared limited by decreased levels (p &lt; .01) of synthetase I. Phosphorylase a activity was increased significantly (p &lt; .025) in placental tissue of diabetic patients as was total phosphorylase (p &lt; .05). Placental weight was decreased in patients with retini-tis proliferans.
These placental enzyme differences noted between the normal and diabetic patient suggest that insulin may play an important role in controlling glycogen metabolism in the human placenta. In diabetes mellitus, increased glycogen concentrations of the placenta may be due to prolonged hyperglycemia throughout gestation and that the elevated term placental glycogen may be responsible for the observed suppressed synthetase I formation and the stimulated phosphorylase a activity found in the diabetic term placenta.
Effect of Insulin on Protein Synthesis
Authors: Manchester Keith L 
Published: December 2014

The mechanism by which insulin controls protein metabolism is not fully understood. Insulin stimulates protein synthesis; it also enhances transport of some amino acids, but the latter action does not appear to be sufficient explanation of the increase in synthesis. The various actions seem to be independent of effects on glucose metabolism. In diabetic muscle there are fewer than normal polysomes, and insulin rapidly enhances attachment of monomers to messenger-RNA. Insulin also increases the effectiveness of cell sap in catalyzing protein synthesis by ribosomal systems. The way in which the hormone may affect either initiation or peptide synthesis is not known.
Experiments are reported bearing on whether availability of amino acids could be a mechanism by which effects of insulin are mediated. Activity of liver and muscle soluble fractions declines on fasting and, for the latter tissue, possibly also on a low protein diet. Sap from fasting animals allows a much smaller response of isolated ribosomes to added amino acids. Availability of glutamate in amino acid mixtures may be of special importance. However, insulin can influence the activity of the sap fraction of diaphragm muscle during incubation without the presence of amino acids in the medium. Understanding of what mechanisms are involved will depend on resolution of the critical sap factors.
Molecular Basis of Insulin Action: Contributions of Chemical Modifications and Synthetic Approaches
Authors: Zahn Helmut , Brandenburg Dietrich , Gattner Hans-Gregor 
Published: December 2014

Current methods used in the preparation of modified insulins for investigating structure-activity relations are briefly discussed. Several chemical degradation and semisynthetic procedures are outlined which were used in the authors' laboratory for the preparation of molecularly homogeneous insulin analogs and derivatives. Des-PheB1 insulin was obtained through selective Edman degradation of insulin, Arg-GlyAl insulin was synthesized by elongation of A-chain S-sulfonate, and this was followed by combination of Arg-GlyA1 chain with natural B chain S-sulfonate. The preparation of [p-iodo-PheB1] insulin was accomplished by removal and replacement of PheB1. Monoacetyl insulins, substituted at GlyA1 or LysB29, respectively, were obtained via partial acetylation of insulin as well as by acetylation of the separate chains. The five compounds could be crystallized in the presence of zinc.
Two insulin derivatives with split A7-B7 disulfide bond, [di(S-carboxymethylcysteine)A7,B7] insulin and [di(S-sulfocysteine)A7,B7] insulin, were obtained through selective electrolytical reduction or partial sulfitolysis.
Some biological and immunological properties of these and seven other modified insulins are presented. The N-terminus of the A chain is highly sensitive to chemical alterations, with the biological activity decreasing in the following order: substitution &gt; removal of the NH2 group &gt; removal of Gly &gt; removal of Gly and lie. The deletion of PheB1 causes no activity loss; the A7-B7 bond can be cleaved and full or at least partial activity be retained.
In view of the scope and limitations of both semisynthetic and synthetic methods, both approaches will be required in future work to prepare potentially important analogs based upon predictions from the three-dimensional structure of insulin as determined by x-ray analysis.
Synthesis of Polypeptides Related to Porcine Proinsulin
Authors: Yanaihara Noboru , Hashimoto Tadashi , Yanaihara Chizuko , Sakagami Masanori , Sakura Naoki 
Published: December 2014

Syntheses are described of eleven protected peptide fragments which cover the entire sequence of porcine proinsulin and of two partially protected polypeptides which correspond to the 17–84 and 15–84 amino acid sequences, respectively, of porcine proinsulin.
The amino acid sequences of the two partially protected polypeptides are illustrated in the text. In these peptides, the sulfhydryl group of cysteine is protected with the ethylcarbamyl function, and the s-amino group of lysine is blocked with the formyl function. The partially protected octahexacontapeptide I cross-reacted with anti-synthetic porcine connecting peptide antisera to the same extent as did the porcine proinsulin or the synthetic connecting peptide. Heptacontapeptide II cross-reacted with antisera to porcine proinsulin and slightly with antisera to porcine insulin.
Nutrient Regulation of Insulin Secretion in Human Subjects
Authors: Kipnis David M 
Published: December 2014

Of all the known secretogogues, glucose is the only one that produces a biphasic secretory response (an early, rapid release of insulin followed by a long, sustained release) and is the only metabolite that stimulates both insulin secretion and biosynthesis at physiologic concentrations. The initial phase is a major determinant of the rate at which the organism utilizes glucose.
An enteric receptor system in man recognizes whether glucose is being ingested or given parenterally. Dynamics of insulin secretion following oral glucose differ markedly from those following parenteral administration. It is suggested that the excessive plasma insulin levels in some maturityonset diabetics during an oral GTT are related primarily to the enteric receptor system and to a delayed release of insulin. Normally, glucose is extracted by the liver due to the early release of insulin. A delay in the release of insulin by maturity-onset diabetics permits glucose to escape hepatic extraction. Thus, the glycemic stimulus is much greater. Known enteric secretogogues enhance the secretory effect of the elevated plasma glucose. Hypoglycemia may develop.
A critical level of glucose is needed to demonstrate the enhancement of insulin secretion by glucagon in children. Intravenous glucagon failed to elicit insulin release when plasma glucose was below 50 mg. per 100 ml.
It is suggested that the genetically determined defect in diabetes mellitus involves the glucoreceptor mechanism. The inability to perceive a glucose signal accounts for the hypoinsulinemic response observed in prediabetic subjects. The insulin-resistant characteristic of the obese state is a secondary adaptation to the hyperinsulinemia produced by excessive carbohydrate intake. It may represent an adaptive mechanism whereby the individual who eats excessive carbohydrate is protected from intermittent hypoglycemia.
The Glycemic Response to Arginine in Man
Authors: Felig Philip , Marliss Errol 
Published: December 2014

To determine the mechanism of the glycemic response to administration of arginine in man, incorporation of arginine-U-C-14 into blood glucose was investigated in postabsorptive subjects given an intravenous infusion of 30 gm. of Larginine monochloride containing 50 μCi of L-arginine-UC-14. As expected, a prompt increase in blood glucose and serum insulin levels was observed. However, whereas the maximal increment in blood glucose of 15 to 22 mg./100 ml. occurred within twenty to thirty minutes of initiation of the infusion, recovery of arginine-C-14 in blood glucose was not detectable until after thirty to fifty minutes, reaching peak levels at 120 min. In subjects given only the tracer dose of arginine-C-14 in whom serum insulin concentration remained at postabsorptive levels, incorporation of C-14 into blood glucose was detectable within ten minutes.
It is concluded that the glycemic effect of arginine cannot be explained on the basis of gluconeogenesis from this amino acid. The insulinogenic action of arginine may contribute to the delay in incorporation of this amino acid into glucose.
Hyperglycemia, Hypoglycemic Attacks, and Production of Anti-Insulin Antibodies Without Previous Known Immunization: Immunological and Functional Studies in a Patient
Authors: Følling I , Norman N 
Published: December 2014

A forty-two-year-old man with hyperglycemia and pronounced reactive hypoglycemia after meals and oral glucose is reported. He produced anti-insulin antibodies without previous known immunization.
Labeled insulin, when mixed with the patient's serum, passed with the serum proteins on gel filtration, and was found among the 7S globulins on preparative ultracentrifugation, in the anodic γ-region on agar electrophoresis, and among the anodic γG-globulins on immunoelectrophoresis. The clearance of labeled insulin in vivo was very slow, and the glucose response to intravenous insulin was absent. The free binding capacity in serum was several thousand μU./ml. Acid splitting of the insulin—anti-insulin complexes revealed 7,000 μU./ml. or more of endogenous insulin, and antibodies which bound human and pig insulin better than bovine insulin. After oral glucose the patient's serum insulin increased by 2,300 μU./ml. Some new principles are introduced in the quantitative studies on serum insulin and antibodies. Theoretical restrictions on these and other quantitations are discussed.
The hyperglycemia may be explained by the antibodies binding secreted insulin, and the hypoglycemia by an insulin overshoot from maximally stimulated β-cells when saturation of the binding capacity was approached. Carbohydrate restriction prevented the hypoglycemic attacks. The cause of the antibody production and the properties of the antibodies are discussed.
Effects of Long-term Infusion of Glucagon on Carbohydrate Metabolism, Insulin and Growth Hormone Secretion in Patients with Congestive Heart Failure
Authors: Frey Harald M M , Falch Dagfinn , Forfang Kolbjørn , Norman Nils , Fremstad Dag 
Published: December 2014

Glucagon was given by continuous intravenous infusion for ninety-six hours to eight patients with severe congestive heart failure. The dose was 4 or 2 mg. per hour. Results were similar in both groups and are presented together.
Mean fasting blood sugar increased significantly during infusion (from 87 to 103 mg./100 ml.). Mean fasting serum immunoreactive insulin (IRI) increased considerably (from 9.1 to 32.0 μU/ml.) and mean fasting serum immunoreactive growth hormone (HGH) increased from 2.8 to 11.9 ng./ml.
Intravenous glucose tolerance tests were performed before and during glucagon infusion. The glucose disappearance rate (K-value) declined significantly during the infusions (from a mean of 0.85 to 0.46), although serum IRI responses to the intravenous glucose were much higher than before. Serum HGH levels were not suppressed by the glucose and sometimes even showed a rise.
A carbohydrate-rich meal induced the same rises in blood sugar during glucagon infusion as before, but serum IRI responses were much higher during glucagon, and elevated serum HGH values were not normalized.
It is concluded that long-term infusion of pharmacological doses of glucagon to patients with cardiac insufficiency leads to a state of mild carbohydrate intolerance, characterized by some increase in fasting blood sugar and decrease in glucose disappearance rate, in spite of very considerable rises in serum IRI. This diabetes-like state may be accounted for by elevated levels of serum HGH, although other insulin-antagonistic factors may be involved.
Pancreatic Compartmentalization of Insulin: Evidence for Pituitary Control
Authors: Merimee Thomas J , Fineberg S Edwin 
Published: December 2014

African pygmies who appear to be insensitive to the metabolic effects of human growth hormone (HGH) are insulinopenic after administration of either glucose or arginine. Contrary to our expectation, insulin responses in this group were normal after tolbutamide and glucagon. To clarify this observation, insulin secretion was studied in twenty-nine normal controls and six dwarfs with growth hormone deficiency.
After arginine and glucose, peak insulin responses in controls were, respectively, 90.4 ± 8.6 μU./ml. and 108.0 ± 12.0 μU./ml. In HGH deficient dwarfs, responses were 38.6 ± 6.0 μU./ml. and 40.0 ± 6.4 μU./ml. (p &lt; .01). In controls as well as HGH deficient dwarfs, the mean maximal insulin responses to arginine and glucose were increased two- to fourfold by HGH treatment (5 nig. twice a day for five days). Similar results occurred after ingestion of mixed meals.
Both tolbutamide and glucagon caused normal insulin responses in the HGH deficient group. Mean maximal responses to tolbutamide were 69.4 ± 15.0 μU./ml. in controls and 61.6 ± 7.7 μU./ml. in HGH deficient dwarfs. Mean maximal responses to glucagon were 101.6 ± 19.4 μU./ml. and 102.0 ± 9.4 μU./ml., respectively. Unlike arginine and glucose, HGH had no effect upon insulin responses to either agent in controls.
The data support the division of pancreatic pools of insulin into two major groups: those dependent and those not dependent upon pituitary secretion of HGH.
A Method for the Determination of Plasma Insulin Antibodies and Its Application in Normal and Diabetic Subjects
Authors: Sebriakova M , Little J A 
Published: December 2014

A practical, sensitive and specific method for the assay of antibodies to insulin in human plasma has been developed. This method involves competition for insulin antibody between a constant, trace amount of I-125-insulin and increasing concentrations of unlabeled insulin standard. The insulin standard is prepared from the soluble form of therapeutic insulin that the patient has been receiving. The quantity of antibody is calculated arbitrarily from the amount of unlabeled insulin required to displace 25 per cent of bound I-125-insulin from the antibody. The result is expressed as microunits of insulin antibody per milliliter of plasma. Since this is not the absolute amount of antibody present but does indicate a relative, quantitative immunologic response of each patient to the antigen, insulin, the result is referred to as an antibody index. The method has a precision of 20 per cent and sensitivity of 1 μU./ml. The coefficient of variation is significantly less at higher antibody indices: 8 per cent in the 1,001 to 80,000 range and 22 per cent in the 0.08 to 40 μU./ml. range.
Therapeutic subcutaneous doses of Lente or Sulphated insulin do not interfere with the antibody assay, whereas the interference from Regular insulin continues for several hours. The antibody index declines after withdrawal of insulin therapy and has a half-life of approximately eighteen days. There is no diurnal variation in antibody index. Three newborn infants of insulin-treated diabetic mothers were found to have insulin antibodies.
Relationship Between the Basal Glucose Concentration Glucose Tolerance and Forearm Glucose Uptake in Maturity-onset Diabetes
Authors: Jackson R A , Perry Gillian , Rogers J , Advani Usha , Pilkington T R E 
Published: December 2014

The relationship between the basal glucose concentration, glucose tolerance and peripheral glucose uptake has been studied in nonobese diabetic males not requiring insulin by determining forearm glucose uptake (FCU) during a 100 gm. oral glucose tolerance test (GTT) before and after carbohydrate restriction.
On a normal diet basal glucose concentrations were elevated and glucose tolerance was grossly impaired; the increment in FCU during the CTT (0 to 180 minutes) amounted to 52.8 mg./100 ml. forearm. After carbohydrate restriction basal glucose concentrations were reduced, the glucose tolerance curve was lowered and the increment in FCU rose to 76.5 mg./100 ml. forearm; glucose tolerance, however, expressed as the incremental area under the glucose tolerance curve (0 to 180 minutes), remained unchanged.
Serum insulin responses during the tests were low and uninfluenced by carbohydrate restriction. Blood lactate concentrations were increased by glucose loading before but not after carbohydrate restriction. FFA and β-hydroxybutyrate concentrations fell progressively after glucose loading while, conversely, acetoacetate concentrations were initially unchanged. During the GTT acetoacetate was taken up by the forearm while lactate and β-hydroxybutyrate were released.
In addition, the responses of three diabetics on a normal diet were compared with those of age-matched normal men; in each diabetic FGU was equal to or greater than that in the normal subjects, but nonetheless, the increment in glucose concentrations was several times greater.
The results suggest that in these patients with diabetes [1] the lowering of the glucose tolerance curve by carbohydrate restriction is not synonymous with an over-all improvement in tissue glucose disposal but is due primarily to a fall in the basal glucose concentration and [2] the impairment of glucose tolerance both before and after carbohydrate restriction is predominantly the result of a reduction in hepatic rather than peripheral glucose uptake.
Insulin Patterns in Equivocal Glucose Tolerance Tests (Chemical Diabetes)
Authors: Danowski T S , Khurana Ramesh C , Nolan Sean , Stephan Thorsten , Gegick Charles G , Chae Soo , Vidalon Carlos 
Published: December 2014

Hyperinsulinemic patterns are a well recognized feature of equivocal glucose tolerances of the chemical diabetes type, i.e. those that are neither definitely nondiabetic nor clearly diabetic. A more complete characterization of such insulin responses is obtained when the data are expressed in terms of increments in insulin from the zero time point.
Thus, two patterns of insulin increments after oral glucose become evident when the equivocal zone of glucose tolerance is divided into lower and upper segments. Tests in the lower segment show normal increments at the halfhour point of the test; at one hour these tests show excessive increments which persist throughout the five hours of observation. On the other hand, tests in the upper zone show delays in the serum insulin rise at the half-hour point, followed by normal increments at one hour and excessive increments thereafter. The pattern is the same whether or not obesity is present.
It is suggested that tests in the equivocal zone of Glucose Tolerance Sum values be taken to be indicative of chemical diabetes. Tests with the Sum in the lower half of the equivocal zone could then represent chemical diabetes with mild intolerance stemming from insulin ineffectiveness, since insulin increments in this group are at or above the mean values recorded in nondiabetic controls. On the other hand, chemical diabetes with moderate glucose intolerance and Glucose Tolerance Sums in the upper half of the equivocal zone would be understood to result from a combination of an initial delay in the serum insulin rise followed by normal and then excessive increments in serum insulin with the latter two indicative of insulin ineffectiveness. However, insulin ineffectiveness may also be present at the time of the insulin delay.
High glucose:insulin ratios in tests indicative of chemical diabetes are almost always attributable to higher glucose increments with insulin increments normal or excessive compared to normal glucose tolerances. Deficient insulin increments contribute to the high ratios only at the half-hour point in tests with Glucose Tolerance Sums in the upper zone of equivocal glucose tolerances.
Regulation of Rat Hexokinase Isoenzymes: II. Effects of Growth Hormone and Dexamethasone
Authors: Bernstein Robert S , Kipnis David M 
Published: December 2014

The effects of dexamethasone and growth hormone on hexokinase (HK) isoenzymes and glucose utilization were studied in adipose tissue from young rats. Dexamethasone (0.1 mg./kg. twice a day) caused hyperinsulinemia with normal blood glucose and marked diminution of adipose tissue HK-II after twenty-four and forty-eight hours. HK-I activity was reduced after twenty-four hours but normal after forty-eight hours. There was no change in HK four hours after a single injection of 0.2 mg./kg. Bovine growth hormone (1 mg. daily) had no effect after twenty-four hours, but increased HK-II after forty-eight hours. Plasma glucose and insulin remained unaltered by GH, and HK-I was also unchanged.
Isolated adipocytes showed the same changes as whole fat pads with dexamethasone, aging, fasting and refeeding; GH had no significant effect. HK-I activity under all circumstances was correlated with in vitro lipogenesis from glucose in the absence of insulin, but not with glucose oxidation. Both lipogenesis and oxidation in the presence of insulin (100 μU./1 ml.) werestrongly correlated with HK-II and glucose-6-phosphate dehydrogenase activįties. These results suggest that control of phosphorylation by HK-II may be a mechanism for mediating hormonal actions on insulin-stimulated glucose utilization.
The Course of Diabetic Retinopathy: A Longitudinal Study
Authors: Gerritzen F M 
Published: December 2014

A prospective study was devoted to the spontaneous course of diabetic retinopathy. The retinas of 459 diabetics were photographed every two years for a total follow-up period, planned beforehand, of eight years.
For two-year intervals progression of retinopathy was found in 14 to 29 per cent, a stationary picture in 60 to 69 per-cent, and amelioration in 7 to 17 per cent of cases. For four-year intervals these percentages were 32 to 39, 47 to 57, and 10 to 12, for six-year intervals 39–50, 40–47, and 10–14, respectively. During the total eight-year period, 48 per cent progressed, 38 per cent remained stationary, and 14 per cent improved. When the patients in whom retinopathy developed during the investigation were included, the percentages changed numerically without altering the general trend. The influence of the dropout of patients on the results is emphasized.
The results are compared with the results of other prospective studies.