bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Physical Exercise on Secretion of Growth Hormone, Glucagon, and Cortisol in Obese and Diabetic Children
Authors: Garlaschi Cristina , Natale Berardo di , Guercio Maria Josè del , Caccamo Anna , Gargantini Luigi , Chiumello Giuseppe 
Published: September 2013

The effect of muscular exertion of moderate intensity on blood sugar (BS), plasma levels of growth hormone (GH), glucagon, and cortisol (F) has been studied in endocrinologically normal children with short stature and compared with children with clinical diabetes mellitus and obese children with normal and diminished carbohydrate tolerance.
In diabetic children, physical exertion induces a rise in plasma GH levels comparable to that in controls; in obese children with normal or with diminished glucose tolerance, the rise is considerably smaller.
Physical exertion caused no change in F levels in the groups tested, although basal level in the obese children was significantly higher than in the controls. Basal glucagon levels were similar in all groups and showed no change on physical exertion.
The behavior of GH and glucagon in diabetic children was comparable to that in the controls even where blood sugar level was high.
Alcoholic Ketosis
Authors: Fulop Milford , Hoberman Henry D 
Published: September 2013

Twenty-four chronic alcohol abusers hospitalized during a twenty-seven-month period were suspected of having “alcoholic ketoacidosis” because they had ketonuria or ketonemia with little or no glucosuria. Twenty-one had moderate or severe ketosis, with plasma 3-hydroxybutyrate of 5.2 to 22.5 mmol/L. Fifteen of this group were not diabetic, while six were later found to have mild postprandial hyperglycemia without glycosuria. Three patients who had continued to drink until shortly before admission, though at first suspected of having alcoholic ketosis, were found to have predominant lactic acidosis, with minor elevations of plasma 3-hydroxybutyrate.
In contrast to previously reported patients with “alcoholic ketoacidosis,” severe acidemia was uncommon in this series. Indeed, seven patients were alkalemic, because of coexisting respiratory or metabolic alkalosis.
Most patients had eaten poorly for several days (and usually longer) and had allegedly decreased their alcohol intake during that period. That history, and the usual rapid clearing of ketosis simply by treatment with solutions of glucose and NaCl, suggested that acute starvation was an important factor in the pathogenesis of this disorder.
Four patients were treated with insulin and four with NaHCO3 solutions. In retrospect, the need for either of these treatments was not clear. Two of the twenty-four patients died, one from circulatory failure secondary to hemorrhage and the other from pulmonary edema, but no patient died because of ketoacidosis per se.
Potentiation of Glucose-induced Insulin Release by Glucose in the Isolated Pancreas of Fed and Fasted Rats
Authors: Efendić Suad , Cerasi Erol , Luft Rolf , Gladnikoff Gils 
Published: September 2013

Glucose, apart from its acute insulin-releasing effect, exerts a time-dependent potentiating action on subsequent stimulations of the pancreas.1 The influence of a 24-hour starvation on these two actions of glucose was studied with the completely isolated, perfused rat pancreas preparation.
Starvation had no effect on the time kinetics of the insulin response, but the magnitudes of the early and late insulin-secretion phases were reduced to similar extents. It was demonstrated by using a wide glucose concentration range that the maximal insulin response is not significantly modified by starvation. In contrast, both the threshold of stimulation by and the Km for glucose were higher in the pancrease from fasted rats. Thus, starvation reduces the sensitivity of the islet for the insulin-releasing action of glucose.
When the stimulatory concentrations of glucose were preceded for 40 minutes by the perfusion of 8.3 mM instead of the basal, 4.4 mM glucose, insulin secretion from the pancreas of fed animals was not modified. In contrast, raising the glucose concentration of the equilibrium period to 8.3 mM potentiated markedly the insulin response to subsequent stimulations in the pancreas from fasted rats. This potentiation expressed itself as increase in the maximal response: the Km for glucose was not reduced. Thus a 40-minute pretreatment with 8.3 mM glucose does not correct the diminished sensitivity induced by a 24-hour starvation.
It is concluded that in starvation (1) the sensitivity for glucose of the mechanisms that initiate insulin release is diminished; (2) the sensitivity of the pancreas for the potentiation-inducing action of glucose is augumented. (3) In both respects, the insulin response of fasted rats is similar to that of mildly diabetic subjects. These and other findings3 suggest that the effect of glucose in initiation of insulin release and on generation of a state of potentiation in the islet are mediated by different mechanisms.
Current Concepts of Somatomedin and Other Biologically Related Growth Factors
Authors: Chochinov Ronald H , Daughaday William H 
Published: September 2013

Since the discovery 20 years ago that the growth-promoting effects of somatotropin are mediated through a serum factor(s), research in this area has rapidly expanded. It is the purpose of this review to bring this area of scientific endeavor into perspective.
The first part of this review will deal with aspects of total serum somatomedin activity and its biologic actions and measurements in health and disease. The last part of this review will summarize some of the physical and biologic characteristics of the recently purified “somatomedin-like” substances: somatomedin A, B, and C, NSILA-S (nonsuppressible insulin-like activity-soluble in acid ethanol) and MSA (multiplication-stimulating activity).
Measurement and Partial Characterization of Immunoreactive Glucagon in Gastrointestinal Tissues of Dogs
Authors: Morita Soichiro , Doi Kunihiro , Yip Cecil C , Vranic Mladen 
Published: September 2013

We have reported previously that increasing amounts of immunoreactive glucagon (IRG), measured by four specific antisera, appeared in plasma of depancreatized insulin-deficient dogs. It was therefore concluded that pancreatectomy was not accompanied by glucagon deficiency in the dog, but instead excessive amounts of extrapancreatic IRG could contribute to the diabetic syndrome. In order to locate the source of extrapancreatic glucagon, tissue extracts were assayed with anti-glucagon sera 30-K and K-44, which cross-react minimally with crude gut extracts. IRG was detected in all gastrointestinal tissues and in the salivary glands, but not in extracts of liver, kidney, brain, heart atrium, and adenohypophysis. Immunologic dilution curves of extracts from all gastrointestinal tissues were parallel to those of the pure pancreatic glucagon standard, and both antisera (30-K and K-44) measured the same concentrations. The highest concentration of gastrointestinal IRG was found in the fundus and corpus of the stomach. Presence of IRG in gastrointestinal tissues of depancreatized dogs indicates that gastrointestinal cells can not only secrete but also store large amounts of IRG.
Extracts of mucosa of stomach fundus were further purified by gel filtration on Biogel P-30 columns. The immunoreactivity in the eluate was assayed by 30-K and a strongly crossreacting antibody, K-4023. One pooled fraction corresponding to marker pancreatic glucagon in its elution volume was found to contain the largest amount of IRG and the highest specific immunoreactivity (IRG/protein concentration). This fraction showed also the highest activity in a glucagon-receptor assay system. Disc gel electrophoresis in the presence of urea resolved this fraction into three immunoreactive components, one of which was identical to pancreatic glucagon in its electrophoretic mobility. It appears, therefore, that mucosa of the upper stomach in the dog contains a polypeptide similar to pancreatic glucagon.
We conclude that (a) hyperglucagonemia in the dog can result from excessive secretion of IRG not only by the pancreatic α cells but also by cells of the gastrointestinal tract; (b) the highest IRG concentration was found in fundus and corpus of the stomach and lower concentrations throughout the gastrointestinal tract; (c) the IRG component in the stomach displayed immunologic and physical properties similar to pancreatic glucagon.
Metabolism of Forearm Tissues in Man: Studies with Glucagon
Authors: Pozefsky Thomas , Tancredi Robert G , Moxley Richard T , Dupre John , Tobin Jordan D 
Published: September 2013

The role of glucagon in regulating peripheral tissue metabolism in man was assessed in the present studies. To do this, glucagon was infused for two hours into the brachial artery to produce a high but physiologic increment in the glucagon content of arterial blood supplying ipsilateral tissues. Metabolic effects on muscle and on subcutaneous adipose tissue plus skin were sought in seven overnight-fasting subjects and seven subjects starved briefly (60 hours).
In the overnight-fasted group the infusion increased bassl glucagon concentration by 1,216 pg./ml. but was without effect on forearm tissue metabolism of glucose, lactate, glycerol, or amino acids. Starvation significantly reduced basal insulin (11.0 to 7.4 μU./ml.) and increased endogenous glucagon (116 to 134 pg./ml.). Basally, there was substantial ketone utilization and a decrease in glucose consumption by both muscle and subcutaneous adipose tissue plus skin. The glucagon infusion increased basal glucagon by 784 pg./ml. Muscle balances of glucose, lactate, acetoacetate, amino acids, and glycerol were unaffected. The metabolism of glucose, lactate, acetoacetate, glycerol, and free fatty acids by subcutaneous adipose tissue plus skin was also unchanged. It is concluded that physiologic increments of glucagon lasting two hours are without effect on forearm tissues in overnight-fasted and briefly starved man.
Cyclic Nucleotides in Pancreatic Islets: Tolbutamide- and Arginine-induced Insulin Release
Authors: Charles M Arthur , Lawecki January , Steiner Alton L , Grodsky Gerold M 
Published: September 2013

With the use of isolated rat islet perfusion, levels of the islet cyclic adenosine 3′ ,5′-monophosphate (cAMP) were compared with dynamic insulin secretion induced by tolbutamide and arginine. Tolbutamide elevated islet cAMP rapidly and augmented both glucose-induced islet cAMP levels and insulin secretion; arginine, however, did not elevate islet cAMP but did enhance glucose-induced insulin secretion. Since the latter result could have been modulated by cyclic guanosine 3′,5′-monophosphate, this cyclic nucleotide was also measured and found to remain unchanged during stimulation of insulin secretion by arginine and a combination or arginine and glucose.
Thus, the action of tolbutamide appears to be modulated in part by cAMP, whereas arginine appears to augment insulin secretion independently of cyclic nucleotides.
Structural Studies of Insulin and Insulin Derivatives Using Various Immunologic Indicators and Antibody Populations
Authors: Arquilla Edward R , Dorio Raymond J , Brugman Thomas M 
Published: September 2013

These studies suggest that the immunologic indicator in the radioimmune assay, 125I-iodoinsulin, selects antibody populations from within the antiserum that interact with determinants distant from the solvent surface on the insulin molecule to which iodine is substituted. Evidence is presented that the connecting peptide of proinsulin is in close proximity to regions on the solvent surface of the A-chain of insulin that include the tyrosyl residues at A-14 and A-19.
A marked immunologic cross-reaction between derivatives of insulin with perturbations in the regions of tyrosyl A-14 and A-19 was noted in the radioimmune assay employing desalanine-(B-30)-desasparagine-(A-21)-insulin antiserum. This observation is consistent with the presence of a restricted population of antibodies in such antisera that is directed toward immunologic determinants in or near the insulin dimer site.
The apparent immunologic activity of insulin derivatives depends on which antibody populations from the antiserum pool can react with the immunologic indicatory employed on the one hand and on the composition of antibodies in that antiserum on the other. These studies indicate that the specificity of antibody populations in a given antiserum can be identified and their levels quantitated with several assay systems, each employing one of a variety of indicators.
Effect of Multiple Daily Insulin Injections on the Course of Diabetic Retinopathy
Authors: Job Didier , Eschwege Eveline , Guyot-Argenton Claudine , Aubry Jean-Pierre , Tchobroutsky Georges 
Published: September 2013

Forty-two diabetic patients on insulin once a day in the early stage of diabetic retinopathy were randomly assigned to one of two kinds of insulin regimen, i.e., single or multiple daily injections. Retinal changes were quantitatively estimated by counting the microaneurysms (MAs) observed on fluorescein angiograms at the posterior pole of the more diseased eye. Baseline characteristics of the two groups were not significantly different. These included duration of diabetes, age at diagnosis, daily dose of insulin, amount of urinary sugar excreted in 24 hours, fasting blood sugar (FBS), and number of MAs. During the follow-up (mean duration of three years) the mean yearly progression in the number of MAs was significantly less in the multiple-than in the single-injection groups: 1.8 ± 0.7 versus 7.2 ± 1.9 (p &lt; 0.01; nonparametric test: p &lt; 0.02). Final values were, respectively, MAs: 15.2 ± 4.9; 33.0 ± 7.9; glycosuria (gm./24 hrs): 20.6 ± 2.5; 27.5 ± 4.3; FBS (mg./100 ml.): 154 ± 15; 195 ± 11. P values comparing the two groups were &lt;0.02, &lt;0.02, and &lt;0.05.
Thus, in this clinical trial, made under routine treatment conditions, the use of divided daily insulin injections was effective in improving diabetic control and delaying retinal changes.
Diabetes Mellitus: Incidence, Prevalence, Survivorship, and Causes of Death in Rochester, Minnesota, 1945–1970
Authors: Palumbo P J , Elveback Lila R , Chu Chu-Pin , Connolly Daniel C , Kurland Leonard T 
Published: September 2013

The incidence and prevalence of diabetes mellitus in residents of Rochester, Minnesota, for 25 years (1945 to 1970) were determined from available medical records. The over-all incidence rate for diabetes is 133 new cases per 100,000 population per year (age-adjusted to 1970 U.S. white population). The rate increased with age for both men and women and was higher among men over 30 years of age. The average annual incidence rates per five-year period for juvenile-onset diabetes mellitus were low and variable and showed little change. Polyuria, polydipsia, glycosuria, lean habitus, loss of weight, and high levels of fasting hyperglycemia at initial diagnosis occurred more frequently in younger than in older patients.
The peak incidence in 1960 through 1964 and the decrease in the following five years may be a reflection of the introduction of the AutoAnalyzer method for blood glucose in 1958. The average annual incidence rates for 1955 through 1959 and 1965 through 1969 were essentially the same. The over-all prevalence for diabetes mellitus is 1.6 per cent, with a higher rate among men than among women over 40 years of age; among school children the rate is 0.1 per cent. Survivorship in the diabetic population is lower than that in the general population. The leading cause of death was coronary heart disease, the death rate from it being higher than for the general population.
Incorporation of 75Se-Selenomethionine into Human Apoproteins: III. Kinetic Behavior of Isotopically Labeled Plasma Apoprotein in Man
Authors: Eaton R Philip , Crespin Stephen , Kipnis David M 
Published: September 2013

The metabolism of lipoprotein-apoprotein was examined in four subjects with normal lipid metabolism and in one subject with type II hyperlipemia by means of isotopic tracer methodology. Studies were performed after intravenous injection of a radioactive amino acid precursor for apoprotein synthesis (75Se-selenomethionine), in both the basal state and following the acute injection of intravenous heparin. Computer technics were used to evaluate a series of multicompartmental models, and a general model is proposed that yields optimum fitting of experimental data for serum free amino acid precursor, very-low-density lipoprotein-apoprotein (VLDapoprotein), and low-density lipoprotein-apoprotein (LDLapoprotein) in man.
The analysis demonstrates that approximately half of the transport of 75Se-apoVLDL from the plasma VLDL pool is converted to 75Se-apoLDL. The acute injection of heparin in two normal subjects results in a two-and-a-half-fold increase in this rate of conversion of 75Se-apoVLDL to 75Se-apoLDL. 75Se-apoLDL is metabolized by rapid transport into a recycling extravascular pool and by irreversible catabolism. The fractional rate of recycling is large relative to the fractional rate of catabolism of apoLDL (3.7:1.0), suggesting extravascular recycling as a potential site of regulation of the plasma concentration of apoLDL. In a patient with type II hyperlipemia, the extravascular recycling pathway is reduced and is not corrected with D-thyroxine therapy. However, this therapy did reduce conversion of apoVLDL to apoLDL in this type II patient.
The kinetic data support the validity of the compartmental model in simulating both normal and pathologic apoprotein metabolism and that perturbation of physiology seen with heparin injection and D-thyroxine therapy. These data support a quantitative role of apoVLDL as a precursor of apoLDL and identify an important recycling pathway of apoLDL metabolism in addition to that of catabolism.
Differences Between Insulin Degradation by Soluble Fractions and Insulin Clearance by Perfused Livers of Normal, Protein-depleted, and Starved Rats
Authors: Sacks H , Pimstone B , Waligora K , Peires L , Weinkove E , Saunders S 
Published: September 2013

The activity of an insulin-degrading enzyme in soluble fractions of liver homogenate (“insulinase”) was compared with clearance of immunoreactive insulin (IRI) by cyclically perfused livers from normal, protein-depleted, and starved rats. Insulin disappearance from normal liver perfusates followed first-order kinetics, and clearances remained unchanged at levels between 1 and 5 nM insulin but fell at Insulin levels above 10 nM. At saturating concentrations (0.13 μM), the maximal rate of insulin removal was 12.5 pmol/mln./gm. wet liver, whereas the maximal degrading velocity of the “insulinase” fraction was 6.0 nmol/min./gm. wet liver. Furthermore, insulin clearance by the intact liver was not influenced by many substances affecting the “insulinase” system. Proinsulin (0.83 μM) acted as a competitive inhibitor, and glucagon, somatostatin, oxytocin, casein (all 1 to 6 μM), and Trasylol (2,000 K.I.U./ml.) inhibited “insulinase” noncompetitively. N-ethylmaleimide (1 mM) inhibited “insulinase” 100 per cent and partly delayed insulin removal from perfusates either because of concomitant reductions in oxygen consumption or because of incomplete titration of either accessible groups at active sites of insulin-degrading enzymes or cofactors.
When results were corrected for liver DNA, protein-depleted and starved rats, respectively, showed 80 per cent and 56 per cent of control “insulinase” activities (p &lt; 0.005 and p &lt; 0.005), but their intact livers cleared physiologic concentrations of insulin at similar.rates to those of controls. These differences, coupled with the lower saturability and probable higher affinity of the insulin removal process by the intact liver and the lack of inhibition of this process by “insulinase” inhibitors, suggest that the plasma membrane of the structurally preserved liver cell plays a physiologic role in the regulation of the rate of insulin catabolism either by degrading insulin itself or by limiting insulin delivery to degrading systems in the intracellular compartment.
Effects of Exogenous Hyperglucagonemia in Insulin-treated Diabetics
Authors: Raskin Philip , Unger Roger H 
Published: September 2013

This study was designed to determine if hyperglucagonemia approximating that believed to be present in the portal vein of poorly controlled diabetics can exert metabollcally deleterious effects in insulin-treated diabetics. Three juvenile-type diabetics and one maturity-onset-type patient were given glucagon intravenously at a dose of 6 ng./kg./min. for 24 hours while receiving a continuous infusion of Insulin. This raised their plasma IRG levels from an average of 122 ± 15 pg./ml. on the control day to 594 ± 60 pg./ml. Mean plasma glucose concentration, measured at two-hour intervals around the clock, averaged 200 ± 20 mg./dl. on the control day and increased significantly in all four patients to 293 ± 18 mg./dl. (p &lt; 0.05) during glucagon administration; fasting glucose rose from 138 ± 10 mg./dl. to 201 ± 17 (p &lt; 0.05). Glucose excretion rose significantly from the control value of 36 ± 14 gm. per 24 hours to 152 ± 19 gm. per 24 hours (p &lt; 0.05). The excretion of both urea nitrogen and ketones also increased significantly (p &lt; 0.05) during glucagon administration. The three juvenile-diabetic patients also received a glucagon infusion at a rate of only 3 ng./kg./min., and in each evidence of deterioration in metabolic control was observed. In every experiment, termination of the glucagon infusion was followed by a recession in the metabolic abnormalities.
These data indicate that exogenous hyperglucagonemia of the magnitude believed to be present in the portai vein of uncontrolled diabetics can cause metabolic deterioration in diabetics receiving continuous insulin treatment.
Pancreatic Beta Cell Toxicity by Streptozotocin Anomers
Authors: Rossini A A , Like A A , Dulin W E , Cahill G F 
Published: September 2013

D-glucose in the pyranose (ring) form exists as two anomers. The α-anomer is more effective than the β-anomer in promoting insulin secretion, suppressing that of glucagon, and protecting β-cells against alloxan toxicity. Streptozotocin (SZ), a beta cell toxin, is composed of a cytotoxk moiety, 1-methyl 1-nitrosourea, attached to carbon-2 of glucose and exists as either of rwo anomers in the pyranose form. In 24-hour-fasted male rats, predominantly α-or predominantly β-SZ was injected intravenously and plasma glucose levels were obtained 48 hours later. The α-anomer produced significantly greater β-cell necrosis at doses of 30, 35, and 40 mg./ kg. body weight. At higher doses, no differences between the α and βanomers were observed. 3-O-Methyl glucose (3-OMG) protected against both SZ anomers; however, the α-SZ remained more toxic. Larger doses of glucose protected against the lower doses of SZ and, under such conditions, the individual glucose anomers appeared equally potent. Finally, mannitol at comparable molar concentrations was ineffective in protecting against the SZ toxkity.
This study suggests that streptozotocin's beta cell toxicity is mediated through recognition by the beta cell. In addition, 3-OMG and, to a lesser but significant extent, glucose were shown to protect against the streptozotocin toxkity, whereas mannitol did not.