bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemical and Early Overt Diabetes Mellitus in Children: I. Effect of Glucagon on “Insulin Reserve”
Authors: Murthy D Y N , Guthrie R A , Womack W N , Jackson R L 
Published: December 2014

Glucose disappearance rates and serum immunoreactive insulin levels following the infusion of glucose and glucose with glucagon were studied in eleven normal subjects, fortyeight children classified as chemical diabetics, and seventeen children with the recent onset of overt diabetes in the early recovery phase of the disease.
Children with chemical diabetes had significantly lower glucose disappearance rates than the normal controls and significantly higher disappearance rates than the children with overt diabetes. Compared with the normal controls, the change in glucose disappearance rates due to glucagon was significantly reduced in chemical diabetics and absent in overt diabetics.
Normal subjects and chemical diabetics responded to glucose and glucagon infusion by increasing the serum IRI levels. Chemical diabetics formed a heterogeneous group with respect to the serum IRI response to glucagon. Children classified as “late” chemical diabetics, like the overt diabetics, had decreased serum IRI responses to glucagon.
Children with chemical diabetes who have blood sugar values outside the ninety-seventh and third percentiles of the distribution of normal values during an oral glucose tolerance test are already in an advanced (late) stage of chemical diabetes and are likely to have their disease progress rapidly to overt diabetes. Children with “late” chemical diabetes have glucose disappearance rates less than 1.1 per cent per minute, less than +0.3 change in glucose disappearance rates after glucagon stimulation and an impaired serum IRI response to an intravenous infusion of glucose or glucose and glucagon. Identification of children in earlier stages of chemical diabetes is desirable in order to evaluate the feasibility of altering the progressive loss of insulin reserve.
Chemical and Early Overt Diabetes Mellitus in Children: II. Effect of Intravenous Tolbutamide on “Insulin Reserve”
Authors: Murthy D Y N , Guthrie R A , Womack W N , Jackson R L 
Published: December 2014

Blood sugar and serum immunoreactive insulin (IRI) response to a rapid intravenous infusion of tolbutamide was studied in twelve normal subjects, forty-four children with chemical diabetes and ten children with overt diabetes mellitus of recent onset.
The diagnosis of chemical diabetes was based on two or more abnormal oral glucose tolerance tests, separated by at least two months' time interval. Of the forty-four children with chemical diabetes, twenty-four children had one or more blood sugar values outside the ninety-seventh or third percentile during oral glucose tolerance tests (“late” chemical diabetes) and had impaired tolbutamide responses at thirty minutes which were significantly different from normal controls and from the children with overt diabetes.
Serum IRI levels were similar in chemical diabetics and normal subjects. Overt diabetics had decreased IRI responses to tolbutamide. The tolbutamide test as performed will not detect children in the earlier stages of chemical diabetes. Until a more sensitive and reliable test is devised, it is necessary to rely on repeated oral glucose tolerance tests to identify children in the earlier stages of chemical diabetes. Longitudinal studies of a large group of children with chemical diabetes are necessary in order to extend our knowledge of the pathophysiology of the disorder and to establish more specific and reliable criteria to define the stages of the disease.
Cotton-wool Spots in Diabetic Retinopathy
Authors: Kohner Eva M , Dollery C T , Bulpitt C J 
Published: December 2014

In nineteen patients with diabetic retinopathy the appearance and life history of cotton-wool spots were studied by serial color photographs and fluorescence angiograms.
Cotton-wool spots are a feature of both mild and severe diabetic retinopathy but, while their appearance is similar to that in hypertension, the associated capillary abnormalities are more severe. On fluorescence angiograms cottonwool spots are associated with arteriolar occlusion with an area of capillary closure and are surrounded by abnormal dilated capillaries.
Capillary abnormalities precede the development of arteriolar occlusion which is necessary for the development of cotton-wool spots.
Cotton-wool spots persist for long periods. Their mean half-life is 8.1 months in patients under forty years of age and 17.2 months in patients over the age of forty. Even when cotton-wool spots disappear, capillary closure persists. Following yttrium90 implantation of the pituitary gland the half-life of cotton-wool spots was 2.3 months.
A Rat Pancreas-Small Gut Preparation for the Study of Intestinal Factor(s) and Insulin Release
Authors: Penhos Juan C , Wu Ching-Hui , Basabe Juan C , Lopez Nestor , Wolff Frederick W 
Published: December 2014

A technic for in situ perfusion of rat pancreas alone or with a small intestine preparation, which is suitable for studying insulin and/or glucagon secretion and the role intestinal factor(s) has upon it, is described. Krebs- Ringer bicarbonate buffer, containing 4.0 per cent bovine albumin and 80 mg. per 100 ml. glucose with pH adjusted to 7.4, was used as perfusate.
When the pancreas was perfused with a nonrecirculated buffer there was no significant change in the levels of glucose or insulin in the perfusate, while with recirculated buffer, there was a decrease in both measurements.
When additional glucose was added to the perfusate, there was an increase of insulin levels, more marked in the pancreas perfusion with recirculated buffer (possibly pancreatic glucagon plus glucose effect) than in nonrecirculated ones (glucose effect).
In pancreas-intestine perfusion with recirculated buffer, there was a decrease of the levels of insulin and glucose, and when additional glucose was added to the perfusate, there was an increase of the levels of insulin and glucose (possibly pancreatic glucagon and glucose effect).
When glucose was passed through the intestine, there was a marked increase of the levels of insulin which was significantly higher than the previous group studied, probably due to the effects of glucose, pancreatic glucagon and intestinal factors.
It may be possible by the results obtained to separate the effects of the three factors on the release of insulin: glucose, glucagon and intestinal factor(s).
Insulin Secretion in Type I Glycogen Storage Disease
Authors: Lockwood Dean H , Merimee Thomas J , Edgar Paul J , Greene Martin L , Fujimoto Wilfred Y , Seegmiller J Edwin , Howell R Rodney 
Published: December 2014

Patients with type I glycogen storage disease (glucose-6- phosphatase deficiency) have marked hypoglycemia in infancy but tend to become normoglycemic as they grow older. In addition, these patients characteristically demonstrate abnormal glucose tolerance curves. Since a major mechanism for the maintenance of normal blood glucose levels is lacking in this disease, investigation of the levels of circulating insulin and the regulation of its release in a group of such patients was made.
Three well-known stimuli for secretion of insulin in normal man were studied in two adolescent and three adult patients with type I glycogen storage disease. Basal plasma insulin levels were repeatedly approximately 50 to 60 per cent ot normal. Ingestion of glucose alone, glucose plus prtrteiu Or infusion of arginine monochlorid resulted in significantly less than normal increase in insulin.
Insulin-like Activity by Fat Pad Assay and Immunoreactive Insulin: II. Their Occurrence in Fractions by Gel Filtration of Serum
Authors: Kajinuma Hiroshi , Ide Takehiko , Kuzuya Takeshi , Kosaka Kinori 
Published: December 2014

In a previous report, serum insulin was extracted with efficient recovery by salt-ethanol extraction.
As the second method of separation of serum insulin gel filtration was adopted. Dog sera obtained from the pancreatic and the femoral veins were separated into two fractions (A and B) with Sephadex G-50. Fractions A and B corresponded respectively to the major peak of serum proteins and the portion where I-131-insulin added to serum was eluted. Insulin-like activity (ILA) was assayed by rat fat pad and immunoreactive insulin (IRI) by a double antibody method. Significant ILA was demonstrated in both fractions. IRI in serum appeared mostly in fraction B. ILA/IRI ratio was closer to 1.0 in fraction B than in serum. Fraction A tended to have fairly uniform ILA irrespectively of origin of serum, often exceeding the ILA of serum. Fraction A from a depancreatized dog serum had similar degree of ILA. Serum and both fractions stimulated various phases of fat pad metabolism similarly to insulin, including glycogen synthesis. Assays based on four different metabolic parameters gave essentially the same ILA values for both serum and fractions. ILA of fraction A differed from insulin in its nonneutralizability with anti-insulin serum, its poor suppressibility by cysteine, and the lack of parallelism of its regression line with that of insulin. Simple dilution and reconcentration of serum resulted in an increase in its ILA. Presumably, fraction B is primarily due to serum insulin with similar immunological and biological activities to pancreatic insulin. Whether or not ILA of fraction A is related to insulin remains unknown.
Insulin Response to Glucagon: The Opposing Effects of Diabetes and Obesity
Authors: Crockford Peter M , Hazzard William R , Williams Robert H 
Published: December 2014

Glucose and immunoreactive insulin responses to glucagon were studied in thirty-seven subjects with varying degrees of relative body weight and glucose tolerance. Glucagon was administered intravenously as an infusion (0.5 mg./30 min.), followed by the acute injection of 1.0 mg. Insulin and glucose levels rose concomitantly during the infusion, but only insulin values increased significantly following the acute injection, providing separation of the glycogenolytic and insulinogenic properties of glucagon. During the 30 min. following the glucagon injection, glucose levels fell to normal in the nondiabetic subjects but remained elevated among the diabetics.
Obesity was associated with elevated basal insulin levels related to the degree of adiposity (r = .402, p &lt; .02) but independent of glucose tolerance (r = &lt; .030). In all subjects, the insidin responses to both glucagon infusion and injection were in turn related to the basal insulin values. The insulin response to glucagon, when expressed as per cent increment above basal in order to correct for the effect of varying degrees of insulin sensitivity as reflected in that basal level, was in all subjects related in a reciprocal manner to the degree of glucose intolerance as reflected by fasting glucose values (r = 0.891, p &lt; .001). Thus, progressive glucose intolerance was associated with progressively impaired insulin secretion. Direct comparison of subjects classified on the basis of obesity or diabetes confirmed the exaggerating influence of obesity and the limiting effect of diabetes upon the insulin response to glucagon.
Human Fetal Insulin Metabolism Early in Gestation: Response to Acute Elevation of the Fetal Glucose Concentration and Placental Transfer of Human Insulin-I-131
Authors: Adam Peter A J , Teramo Kari , Raiha Niels , Gitlin David , Schwartz Robert 
Published: December 2014

Although insulin has been demonstrated in human fetal pancreas as early as thirteen weeks of gestation, the controls of insulin secretion in the human fetus and the magnitude of placental insulin transfer to the fetus are unknown. In pregnant women, scheduled for therapeutic abortions by abdominal hysterolomy at fifteen to twenty weeks of gestation, the fetal plasma insulin response to glucose infusion and insulin transfer across the placenta were studied as follows: (1) glucose was infused to eight fetuses in situ, and (2) insulin-I-131 was infused continuously for four to six hours to eight pregnant women via peripheral vein.
Insulin was measured radioimmunologically and, following the infusion studies, was precipitated quantitatively by a double antibody method. During fasting, no difference was observed between fetal and maternal plasma glucose or in insulin levels. Although glucose administered to the fetus raised the fetal plasma glucose concentration without changing the maternal level, both fetal and maternal plasma insulin concentrations were unchanged at five and ten minutes. Human insulin-I-131 was not transferred across the placenta and no sequestration of insulin-I-131 occurred in the placenta. Early in human gestation the fetal pancreas appears to be the major source of fetal insulin, and the fetal insulin secretion rate may be relatively unresponsive to acute changes in blood glucose concentration. The placenta acts as a barrier to human insulin-I-131 but does not appear to sequester and catabolize insulin-I-131, as was previously demonstrated in human pregnancies at term.
In Vitro Insulinogenic Effect of Two Monoamine-Oxidase Inhibitors
Authors: Hernández Rodolfo Eduardo , Gagliardino Juan José , Rodriguez Ricardo R 
Published: December 2014

The stimulatory effect of two monoamine-oxidase inhibitors, nialamide and tranylcypromine, upon insulin secretion was studied using the in vitro rat slice pancreas incubation technic. It was found that these drugs stimulated insulin release in the presence of low levels of glucose. They were also able to enhance the insulin release elicited by high levels of glucose.
These results would explain, at least in part, the protective role of MAOI in some types of experimental and clinical diabetes.
Insulin-Resistant Diabetes with Autoantibodies Induced by Exogenous Insulin: Successful Treatment by Insulin Withdrawal
Authors: Karam John H , Grodsky Gerold M , Forsham Peter H 
Published: December 2014

An obese woman was studied over a five-year period, during which time she had three episodes of severe insulinresistant diabetes, associated with a high level of insulin antibodies.
During her second hospitalization, there was no evidence of acute stress, suggesting that in addition to obesity, her extremely high levels of antibodies were interfering with the effectiveness of the administered insulin. These antibodies were shown by immunologic methods to bind both circulating exogenous (bovine) and endogenous (human) insulins. With no other specific therapy except the abrupt halt of insulin, her diabetes improved, her antibody liters declined with a half-life of about twenty days, and the capacity of her plasma to bind both exogenous and endogenous insulin decreased. Antibody levels, although much lower, were still detectable more than eighteen months after discontinuing insulin therapy.
The patient's marked clinical improvement on stopping insulin, suggested that the high levels of circulating antibodies were a factor in maintaining her severe insulin resistance. Treatment with insulin in this patient was not only ineffective but apparently had worsened her diabetes. The excellent results obtained during her third hospitalization emphasize the superiority of supervised diet and enforced weight reduction over insulin as a choice of treatment in this type of patient.
Effect of Insulin on the Conversion of Glucose-C-14 to C-14-02 by Normal and Diabetic Fibroblasts in Culture
Authors: Goldstein Samuel , Littlefield John W 
Published: December 2014

In an attempt to elucidate the basic genetic defect (s) in diabetes, the acute effect of insulin on the conversion of glucose-C-14 to C-14-02 in cultured human diploid fibroblasts was measured under various conditions. Freshly trypsinized cells did not respond to insulin, but after more than sixteen hours in growth medium, a small but significant stimulation, requiring high concentrations of insulin (0.26 U. per ml.) was observed. Stimulation by insulin in various normal strains ranged from 5 to 45 per cent with a mean of 18 per cent (p &lt; .001). C-14-O2 production was approximately linear with time after an initial lag phase and proportional to the number of cells inoculated. Increasing the concentration of glucose in the medium increased C-14-O2 production, with stimulation by insulin apparent at only very low concentrations and at 250 mg. per 100 ml., the highest concentration studied. Experiments comparing the oxidation of glucose-l-C-14 versus glucose-6-C-14 showed that substantial C-14-O2 production occurred via the hexose monophosphate shunt, but that most of the increase in C-14-O2 production in the presence of insulin occurred via the Krebs cycle.
A comparison of basal and insulin-stimulated C-14-O2 production in normal and diabetic fibroblasts revealed no significant differences. Possible explanations for the failure to distinguish between the two groups are discussed.
Early Insulin Synergistic Activity of Growth Hormone
Authors: Mahler Richard J , Szabo Olga 
Published: December 2014

Intravenous injection of growth hormone to the intact rat (0.2 mg./100 gm.) causes significant reduction in the blood sugar within twenty minutes of injection. To determine the influence of CH upon insulin destruction, BGH was injected into intact animals and the animals were sacrificed ten minutes later with removal and incubation of kidney and liver slices in I-131-insulin. There resulted a marked reduction in the rate of insulin degradation. In addition, kidney slices and hemidiaphragms obtained from animals injected with BGH ten minutes previously demonstrated enhanced sensitivity to the in vitro effect of insulin upon glucose uptake and glycogen content.
These observations allow the suggestion that the early hypoglycemic activity of growth hormone may be mediated by a transitory impairment of insulin degradation with consequent metabolic effects upon specific tissues.
Effect of Alloxan on the Enzyme Activity of Microdissected Mammalian Pancreatic Islets
Authors: Dixit Padmakar K , Lazarow Arnold 
Published: December 2014

Quantitative histochemical methods have been used for the assay of 6-phosphogluconic dehydrogenase (6-PGDH), isocitric dehydrogenase (ICDH), peptidase (PEPT), and adenosine triphosphatase (ATPase) in the microdissected islets and acinar tissue obtained from normal and alloxan diabetic rats.
6-PGDH activity of the islets following alloxanization showed an increase at twelve hours; maximal change was observed at seventy-two hours. There was no consistent and significant increase in the enzyme activity of the acinar tissue following alloxanization.
ICDH activity of rat islet was increased significantly at twelve hours but decreased at twenty-four hours after alloxanization. At forty-eight and seventy-two hours the enzyme activity of the islet returned to normal. Enzyme activity of the acinar tissue showed no particular trend, although at twenty-four hours following alloxanization it was significantly lower than in the controls.
Changes in islet peptidase activity were more marked. Following alloxanization the islet enzyme activity decreased significantly up to twenty-four hours; at forty-eight hours it showed marked increase and was between two- and threefold that of the value at twenty-four hours. It should be noted that this increase in the islet peptidase activity coincides with the period of disappearance of the beta cells.
No immediate effect of alloxan injection was noted on the ATPase activity of the rat islet tissues during the first two hours. This is contrary to the reports of some earlierworkers.
Immunological Properties of Bovine Proinsulin and Related Fractions
Authors: Rubenstein Arthur H , Steiner Donald F , Cho Sooja , Lawrence Ann M , Kirsteins Lidia 
Published: December 2014

The immunological interrelationships of bovine proinsulin, its related fractions and insulin are described. Proinsulin has been iodinated and the labeled material purified and characterized. Proinsulin and its intermediate fractions, which could be converted to desalanyl insulin by trypsin, reacted more strongly than insulin or the “nonconvertible” insulin-like material with antiserum to purified proinsulin. The order of reactivity was reversed in favor of insulin when an insulin antiserum was used. Preincubation of the antiserum to purified proinsulin with large quantities of insulin allowed the preferential measurement of bovine proinsulin, and the assay was unaffected by further addition of insulin. The isolated C-peptide from proinsulin was effective in displacing I-131-proinsulin from this antibody.
Human and porcine proinsulin reacted weakly with antisera to bovine proinsulin. The immunological differences between proinsulins are far greater than among the corresponding insulins, and imply that the C-peptide of proinsulin contains major antigenic determinants. It is probable that specific antisera will be needed for the optimal assay of each species of proinsulin.
Synthesis of Liver Glycogen in Starved Alloxan Diabetic Rats
Authors: Hornbrook K Roger 
Published: December 2014

Alloxan diabetic rats are considered unable to synthesize liver glycogen because of a low activity of glycogen synthetase. The present report shows, however, that livers of alloxan diabetic rats have activities of the I-form of glycogen synthetase intermediate between those of starved normal or adrenalectomized rats, and can synthesize substantial amounts of liver glycogenafter refeeding of a chow diet or administration of hydrocortisone. Neither glycogenic procedure, increased the activity of glycogen synthetase in livers of starved alloxan diabetic rats. In contrast, both normal and adrenalectomized rats had increased activities of the I-form of glycogen synthetase three hours after refeeding.
After twenty-four hours of access to food, normal and adrenalectomized rats had liver glycogen contents similar to those found in nonstarved rats, and a markedly decreased activity of synthetase I. Alloxan diabetic rats refed for twenty-four hours also had lowered activity of synthetase I, but the concentration of glycogen was not higher than that found after three hours of refeeding.
These results show that livers of alloxan diabetic rats have sufficient glycogen synthetase activity to synthesize glycogen rapidly, but the ability to accumulate larger amounts of glycogen is limited by an alteration in the control of glycogen synthetase activity by the content of liver glycogen. Also, the effect of hydrocortisone on the activity of glycogen synthetase in normal or adrenalectomized rats is the result of insulin release; however, not all the changes in glycogen metabolism produced by adrenalectomy can be explained by insulin deficiency.
Studies in Patients with Chlorpropamide-Induced Hypoglycemia
Authors: Frey Harald M M , Rosenlund Bent , Sandtrö K 
Published: December 2014

Six patients with hypoglycemia due to chlorpropamide are reported. The common characteristics were old age and/or poor nutritional state.
The serum concentration of chlorpropamide during hypoglycemia was not higher than that seen in a group of chlorpropamide-treated diabetics without hypoglycemia. In both groups, the serum level declined in a rectilinear fashion after the drug was stopped, and the rate of decline was similar in the two groups. The serum level of chlorpropamide in the control group covered a fourfold range at the same dose level, and had no correlation with the degree of diabetic control.
The serum insulin concentration was in two instances somewhat high compared to the low blood sugar, but most of the time was found to be at a low (fasting) level. In three patients no evidence of insulin secretion in peripheral venous blood was found even after stimulation with glucagon, glucose, or meals. In two of them, however, the absence of insulin was transient and present only during the day of hypoglycemia.
It is suggested that diabetics in negative calorie balance are predisposed to hypoglycemia ifthey continue to take chlorpropamide, and that they suffer this complication even with a serum concentration of the drug that is within therapeutic range. The pathogenesis probably does not involve increased peripheral utilization of glucose, but more probably an inhibiting effect on production of glucose by the liver.