bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Glucagon-like Immunoreactivity (GLI)
Authors: Valverde Isabel , Rigopoulou Demetra , Marco Jose , Faloona Gerald R , linger Roger H 
Published: December 2014

The present studies were designed to obtain further information concerning the chemical interrelationships of the fractions of glucagon-like immunoreactivity (GLI) present in gastrointestinal tissues, their biologic activity, and their immunochemical and electrophoretic properties. Chromatography of canine jejunal extracts on a Bio-Gel P-10 column separated GLI into two fractions; one, designated Peak II, eluted with the glucagon-I-131 marker (molecular weight 3,500), while the other, designated Peak I, appeared before the insulin-I-131 marker (molecular weight &gt;6,000). Neither rechromatography, nor incubation in 8 M urea, acetic acid, or mercaptoethanol changed the elution volume of Peak I; however, trypsin caused a major loss of immunoreactivity and a shift of residual immunoreactivity to the postglucagon-I-131 zone.
Peak I was devoid of glycogenolytic activity in the perfusedrat liver, as was its tryptic product, while Peak II was consistently as active as pancreatic glucagon. Immunoprecipitated Peak II was also active, proving that the immunoreactive fraction was responsible for its biologic action.
Unlike pancreatic glucagon, Peak I, Peak II, and the tryptic product of Peak I diluted disproportionately with the less specific antiserum; however, Peak II could not be differentiated from pancreatic glucagon by means of polyacrylamide gel disc electrophoresis.
It is concluded that (1) Peak I does not consist of Peak II bound noncovalently either to itself or to another protein; (2) Peak I and its tryptic product are devoid of glycogenolytic activity while Peak II has the approximate activity of pancreatic glucagon; (3) the glycogenolytic and immunoreactive components in the eluate containing Peak II are probably on the same molecule; (4) both Peak I, its tryptic product, and Peak II are immunologically different from pancreatic glucagon.
Comparative Study of Diabetes Knowledge Among Juvenile Diabetics and Their Parents
Authors: Collier Boy N , Etzwiler Donnell D 
Published: December 2014

One hundred and twenty-nine children with diabetes from fifty-eight junior and senior high schools in the Minneapolis- St. Paul area and their parents were given a thirty-four-item test to evaluate their knowledge of diabetes and to determine if there were significant differences in understanding. Areas of deficiency were noted particularly involving understanding of diet, acidosis and alterations in management that occur with changes in activity or illness.
Descriptive material is presented indicating that there is high correlation of knowledge levels between diabetic children and their parents.
Glucagon and the Insulin:Glucagon Ratio in Diabetes and Other Catabolic Illnesses
Authors: Unger Roger H 
Published: December 2014

The biologic opposition which insulin and glucagon exert upon the liver and adipose tissue suggests that the relative concentrations of these two hormones which perfuse these tissues may determine their net nutrient balance.
A review of recent studies of plasma glucagon and insulin levels reveals that the insulin:glucagon ratio (I/G) varies inversely with need for endogenous glucose production, being lowest in total starvation and highest during loading with exogenous carbohydrate. Similarly, the infusion of the glucose precursor, alanine, which in the fasting state causes a fall in I/G, a “catabolic response,” increases I/G during a glucose infusion, an ”anabolic response,/ which must spare alanine from gluconeogenesis. The same bihormonal relationship to need for glucose production has been observed after a protein load; normally after an overnight fast I/G rises in response to a beef meal, an anabolic response, while in the carbohydrate-deprived subject, the I/G does not rise, remaining at a catabolic level; during a glucose infusion the ingestion of a beef meal induces a greatly exaggerated anabolic rise in I/G.
These findings are believed to account for certain previously poorly understood clinical observations. They may explain the so-called “protein sparing action” of glucose and the salutory nutritional effect of intravenously administered amino acid preparations when glucose is also provided in large quantities. The inability of diabetics to increase their I/G generally parallels their catabolic state, and, by stimulating glucagon but not insulin, tissue breakdown due to infection or trauma may further reduce the I/G and cause metabolic deterioration. The possible role of the I/G in the response to burns, trauma, infection, and malignancy is considered.
Glucagon and Insulin Release: Influence of Drugs Affecting the Autonomic Nervous System
Authors: Vance James E , Buchanan Keith D , Williams Robert H 
Published: December 2014

Isolated rat islets of Langerhans were used to study the direct effect of autonomic nervous system compounds on immunoreactive glucagon (IRG) and insulin (IRI) release. None of the substances affected IRG release. Epinephrine (10μ.M) and norepinephrine (10μM) blocked IRI release in response to 150 mg./100 ml. glucose but did not block the effect of 300 mg./100 ml. glucose. Acetylcholine (3 μM) stimulated IRI release but isoproterenol had no effect.
Because the adenylcyclase system may play a role in adrenergic receptor mechanisms, the effects of substances which alter cellular levels of cyclic AMP were also studied. Again, none of the compounds altered IRG levels in the incubation media. Aminophylline (100 μM) stimulated IRI release but dibutyryl cyclic AMP and prostaglandin Ex were without significant effect.
The results suggested that neither autonomc nervous sys tem compounds or the adenylcyclase system directly affect IRG release. The physiolugical significance of the direct inhibitory effect of substances with alpha adrenergic properties on IRI release is questioned in view of the very high concentration required for effect.
Experimental Diabetic Hyperosmolar Syndrome in Rats
Authors: Bavli Samuel , Gordon Edwin E 
Published: December 2014

The diabetic hyperosmolar syndrome occurs predominantly in maturity-onset diabetics and is characterized by extreme hyperglycemia, hyperosmolarity of plasma, and absence of ketoacidosis. A syndrome bearing a marked resemblance to the human disease can be produced in rats. The three prerequisites for the development of the experimental syndrome are: (1) moderate nonketotic diabetes (induced by either streptozotocin or alloxan) ; (2) treatment with hydrocortisone acetate; and (3) water deprivation.
Plasma glucose concentrations in cortisol-treated, waterdeprived diabetic rats ranged from 838 to 1,488 mg./100 ml. and were significantly higher than those of control diabetic or ketoacidotic animals. Neither cortisol treatment alone nor water deprivation alone was adequate to raise plasma glucose concentration above that of control diabetic rats. The blood pH, acetoacetate, and β-hydroxybutyrate of cortisoltreated, water-deprived diabetic rats did not differ significantly from the diabetic control values, but all three of these parameters were different from those of ketoacidotic rats. Neither cortisol treatment, nor water deprivation, nor a combination of the two treatments significantly affected these parameters in nondiabetic rats.
By analogy with the experimental syndrome, it is suggested that administration of corticosteroids may play a role in the development of the human hyperosmolar syndrome in some patients. Furthermore, the fact that water deprivation was necessary for the production of the experimental syndrome suggests that the extreme dehydration seen in the human hyperosmolar syndrome is not merely a consequence of hyperglycemia, but also a factor in the development of the extreme hyperglycemia.
Osseous Lesions of the Foot in Diabetic Neuropathy
Authors: Friedman Sandor A , Rakow Robert B , Pod D 
Published: December 2014

The clinical course and foot roentgenograms of twentytwo consecutive patients with severe diabetic neuropathy were reviewed. All but one patient had skin breakdown with adequate arterial circulation. Cutaneous lesions responded well to local care, the majority healing within one month, despite widespread bone destruction. In seventeen of the twenty-two cases, (77 per cent), there were multiple bone lesions that tended to be bilateral and to follow the peripheral distribution of the neuropathy. The osseous abnormalities were radiologically indistinguishable from osteomyelitis except for a characteristic thinning of the metaphysis of proximal phalanges. Follow-up X rays showed progressive bone destruction in four patients although they had no further difficulty with their feet.
We conclude that widespread osteopathy of the foot occurs frequently in severe diabetic peripheral neuropathy and has a better prognosis than osteomyelitis, from which it must be distinguished clinically.
Plasma Insulin in Reactive Hypoglycemia
Authors: Luyckx A S , Lefebvre P J 
Published: December 2014

Among 663 standard four-hour oral glucose tolerance tests (OGTT) performed in a Department of Internal Medicine, forty-seven curves demonstrated reactive hypoglycemia of 45 mg. per 100 ml. or less at one or more occasions. Subsequent analysis of the records of the corresponding patients allows their partition into the following groups: IA. Obesity (11), IB. Obesity with chemical diabetes (9), II. Postgastrectomy syndrome (3), III. Chemical diabetes without obesity (1), IV. Renal glycosuria (7), V. Isolated reactive hypoglycemia (16).
In order to determine the role of plasma insulin in the pathogenesis of the syndrome, the insulin response of each group of subjects presenting reactive hypoglycemia was compared to that of a control group of similar age, sex and weight with similar pathological findings but without reactive hypoglycemia. The results indicate that plasma insulin values can not account for the reactive hypoglycemia in the groups IA, IB, III and IV, and thus other factors may be responsible for the occurrence of hypoglycemia in most cases of this syndrome.
In contrast, an exaggerated insulin response exists in group II, and in seven out of the sixteen cases of isolated reactive hypoglycemia.
No correlation was found between the presence of clinical symptoms evoking reactive hypoglycemia during the usual life and the severity of the hypoglycemia recorded during the OGTT.
Insulin Secretion Studied in the Perfused Rat Pancreas: I. Effect of Tolbutamide, Leucine and Arginine; Their Interaction with Diazoxide, and Relation to Glucose
Authors: Basabe J C , Lopez N L , Viktora J K , Wolff F W , McNeal B , Mongelli C , Wcinhardt K , Baukal A 
Published: December 2014

Glucose produced a diphasic pattern of insulin secretion in the perfused rat pancreas. Both phases were blocked by diazoxide. Tolbutamide alone produced a monophasic insulin secretion which was decreased by diazoxide on an equimolar basis.
When tolbutamide was added to a perfusion containing glucose and diazoxide, it reversed the blocking effect of diazoxide on glucose by reestablishing the diphasic pattern of glucose-stimulated insulin secretion. This effect was also produced in an equimolar fashion.
Leucine induced a diphasic pattern of insulin secretion. When perfused together with glucose, an additive effect was apparent in both phases. Diazoxide blocked the secretion of insulin stimulated by leucine alone or by leucine plus glucose.
Arginine (16 mM) failed to stimulate insulin secretion, but a clear increase was observed at 26 mM concentration. An additive effect of arginine and glucose was observed in the presence or absence of 10 mg. per cent diazoxide, but was blocked by increased diazoxide concentration (25 mg. per cent). The results show that the diazoxide effect on the arginine-induced insulin secretion is related to the concentration of diazoxide used, and suggests that the stimulatory action of arginine and glucose is channelled through one identical mechanism, triggering insulin release in the beta cell.
Effect of Streptozotocin on Glucose-induced Insulin Secretion by Isolated Islets of Langerhans
Authors: Golden P , Baird L , Malaisse W J , Malaisse-Lagae F , Walker M M 
Published: December 2014

The present experiments were designed to investigate the immediate action of streptozotocin upon the beta cell by measuring its effect upon glucose-induced release by isolated islets of Langerhans. The results demonstrated a dose-related inhibition of glucose-induced secretion during the first two hours of incubation, with the inhibition most marked in the second hour. The same level of inhibition was achieved in the second hour regardless of whether the drug was present for both hours or for just the first hour.
Nicotinamide showed a dose-related protection against the inhibitory action of streptozotocin whereas nicotinic acid did not. Further, nicotinamide showed a protective trend even when added one hour after streptozotocin—indicating that no irreversible change in the insulin secretory mechanism had been elicited over the first hour of incubation. An enhancement of glucose-induced secretion was observed with nicotinamide alone. Nicotinamide was not able to protect against the inhibitory action of mannoheptulose and the latter had no significant effect upon streptozotocin's action.
It is concluded that the early hyperglycemia induced by streptozotocin is the result of a direct action of streptozotocin on the beta cell and that the same biochemical lesion may be responsible for both the impairment of insulin secretion and eventual beta-cell destruction. Finally, the demonstration of a protective action of nicotinamide at the site of the beta cell suggests that the nicotinamide adenine dinucleotide (NAD) level of the beta cell may be critical for maintenance of normal function.
Insulin Secretion in Protein-Calorie Malnutrition: I. Quantitative Abnormalities and Response to Treatment
Authors: Becker Dorothy J , Pimstone Bernard L , Hansen John D L , Hendricks S 
Published: December 2014

Immunoreactive insulin (IRI) responses to oral and/or intravenous (IV) glucose were measured in kwashiorkor and marasmus. Responses were expressed either as peak IRI levels attained or as insulin-glucose ratios. Similar measurements were made in normal controls.
After oral glucose, insulin secretion was abnormally low in every patient with kwashiorkor and in most of the marasmic cases. After IV glucose, normal insulin responses were noted more often, presumably associated with the greater glycemic stimulus. This was particularly noticeable in marasmus.
In both groups of subjects there was improvement after three to six weeks therapy, but this was much more striking after oral glucose. However, in many patients, insulin secretion remained subnormal or even deteriorated at this time, when nutritional status had greatly improved. Two to ten months later however, insulin levels were judged to be within normal limits in these cases. Children known to have suffered from kwashiorkor ten years previously likewise had normal insulin responses in 90 per cent of cases.
Augmented stimulation by glucose plus glucagon revealed some pancreatic insulin reserve in half the untreated patients studied. Yet the responses to augmented testing improved still further in three of five cases after therapy.
Insulin secretion is grossly impaired in kwashiorkor and marasmus. However, it is increased in many cases either by a greater glycemic stimulus or by adding glucagon to the glucose load. This suggests a “sluggishness” of insulin release after glucose under conventional conditions of testing in these cases. The disproportionate improvement after therapy in the insulin response to oral, as opposed to IV, glucose, may provide some evidence that an impaired gut betacytotrophic mechanism is partly responsible for the altered release mechanisms.
Studies of Insulin and Growth Hormone Secretion in a Subject with Hepatoma and Hypoglycemia
Authors: Colwell John A , Wilber John F 
Published: December 2014

SUMMARY
Studies of immunoreactive insulin (IRI) and human growth hormone (HGH) secretion were undertaken in a subject with chronic hypoglycemia associated with hepatoma. Fasting IRI concentrations were below 3 μU./ml. at glucose concentrations of 30 mg./100 ml. IRI secretion was not stimulated by acutely administered glucose, tolbutamide, glucagon or arginine. IRI concentrations rose after tolbutamide when plasma glucose was raised to 100 mg./100 ml. by sustained glucose infusion. Fasting ILA (muscle, adipose) levels were not elevated.
Fasting HGH concentrations were below 5 mμg./ml.; secretion was stimulated by arginine despite hypoglycemia. During glucose administration, HGH concentrations rose to 45 mμg./ml. as FFA levels fell from 2,250 to 233 μEq./L. Estimated total glucose utilization rate was high (7.5 mg./kg./hr. at a plasma glucose concentration of 100 mg./100 ml.).

Conclusions
(1) Glucose, or some metabolic product is required for human insulin secretion; (2) HGH secretion after arginine is not inhibited at low glucose concentrations; (3) FFA may exert an inhibitory role in HGH regulation; (4) Hypoglycemia in our subject with hepatoma was associated with increased glucose utilization, not with hyper-insulinism.
Serum Insulin and Growth Hormone Values in Children during the Oral Glucose Tolerance Test
Authors: Cole Harold S , Epel Rosa 
Published: December 2014

Three-hour oral glucose tolerance tests were performed on 125 nonobese children in three age groups: One-and-one-half to less than four years, four years to less than eight years and eight to twelve years of age. All children were in good health and had negative family histories for diabetes. Oral glucose was administered according to age and weight. Capillary blood was collected and analyzed for blood sugar and serum insulin and growth hormone.
All insulin and growth hormone analyses were performed on specimens from children whose blood sugar values during the oral glucose tolerance test conformed with previously established standards for normal controls.
No significant differences were found either for insulin or growth hormone at any of the testing periods between all age groups or between the sexes.
Insulin values reached their peak sixty minutes after ingestion of glucose and returned toward fasting levels at 180 min. The highest level of growth hormone was the fasting value. A decrease occurred after administration of oral glucose with a rising trend at the 180 min. testing period. Five control children who received a nonglucose-containing vehicle orally showed no statistically significant changes in growth hormone values due to the stress of multiple finger sticks.
The Effect of Insulin on Fat Cells: An Insulin Degrading System Extracted from Plasma Membranes of Insulin Responsive Cells
Authors: Crofford Oscar B , Rogers Nancy L , Russell Wilson G 
Published: December 2014

The major effects of insulin on glucose, fatty acid and amino acid metabolism and on ion flux are initiated by the interaction of insulin with certain unidentified components of the cell membrane. These early events in the action of insulin were studied further with purified plasma membranes prepared from rat epididymal adipose cells.
The binding of 125I-labeled insulin to fat cell plasma membranes gives results quantitatively similar to those reported previously with unlabeled insulin. In addition, intact fat cells, plasma membranes from fat cells and a soluble extract from the plasma membranes contain a highly active insulin degrading system. Both the capacity of the plasma membranes to bind insulin and the insulin degrading activity of the membrane extract can be inhibited by the addition of unlabeled insulin to the incubation medium even though albumin is present in excess. The degraded products have not been fully identified but are soluble in 10 per cent trichloroacetic acid, nonreactive with anti-insulin guinea pig serum, nonadsorbable to a 125I adsorbing resin and, therefore, probably represent fragments of the insulin molecule. When isolated fat cells are treated with trypsin they become insulin unresponsive. Plasma membranes derived from such cells have a reduced capacity to bind insulin, and the insulin degrading system of the membranes or in the soluble extract from the membranes is inactive. This suggests that both the insulin receptor and the insulin degrading system are located on the external surface of the plasma membranes of the fat cells. It is postulated that an insulin degrading system of the plasma membrane may be one of the physiological mechanisms by which the response of fat cells to insulin is terminated.
Three-Dimensional Atomic Structure of Insulin and Its Relationship to Activity
Authors: Blundell T L , Cutfield J F , Cutfield S M , Dodson E J , Dodson G G , Hodgkin D C , Mercola D A 
Published: December 2014

The three-dimensional structure of the insulin molecule has been determined by single crystal x-ray analysis. The two chains are compactly arranged with the A chain lying above a central helical region of the B chain. From each end of the helix the terminal residues extend as arms, and the A chain is enclosed between these. This limits the A chain to one surface of the molecule. Two surfaces, made up of B chain residues, are nonpolar and are buried by the aggregation of the molecule into a dimer and then into a hexamer. The insulin molecules of the 12,000 molecular weight dimer are related by an approximate twofold axis. Three such dimers can come together and in the presence of zinc ions form the stable 36,000 molecular weight hexamer. The three dimers have identical structures and are related by a threefold axis. The approximate twofold axis of the dimer is perpendicular to this. There is good evidence that insulin is stored in the granule as small crystals of this hexamer.
The A chain terminal residues A1 glycine, A5 glutamine, A19 tyrosine and A21 asparagine are on the surface of the molecule. They are invariant and not involved in the aggregation of the molecule. Their deletion affects both the structure and activity of insulin. Substitution at A1 glycine, especially of bulky groups, reduces activity substantially but seems to affect the molecular structure less. In proinsulin the connecting peptide appears to cover these residues. Therefore the surface A chain terminal residues apparently are important to the molecule's activity.