bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Cyclic AMP in the Control of Carbohydrate Metabolism
Authors: Sutherland Earl W , Robison G Alan 
Published: December 2014

Cyclic AMP plays an important role in the regulation of metabolism generally. Emphasis in the present review has been placed on carbohydrate metabolism, but lipid metabolism has also been discussed to some extent. The chief role of cyclic AMP in several tissues seems to be to facilitate or promote the mobilization of glucose and fatty acid reserves. In the liver, glucagon and the catecholamines cause an increase in the intracellular level of cyclic AMPby stimulating adenyl cyclase. This increase in the level of .cyclic AMP leads to a net increase in hepatic glucose production by at least three mechanisms: stimulation of phosphorylase activation, suppression of glycogen synthetase activity, and stimulation of gluconeogenesis. The catecholamines also stimulate adenyl cyclase in muscle and adipose tissue. Among the principal effects of cyclic AMP in these tissues are glycogenolysis in muscle and lipolysis in adipose tissue.
Another role of cyclic AMP is to enhance or promote the release of insulin from pancreatic beta cells. Insulin then travels to the liver and adipose tissue to suppress the accumulation of cyclic AMP, and may also antagonize the action of cyclic AMP in muscle. Cyclic AMP is thus seen to mediate the actions of several catabolic hormones as well as promote the release of an anabolic hormone which acts in part by opposing cyclic AMP.
Since cyclic AMP is involved in the release as well as several of the actions of insulin, the possible role of cyclic AMP in diabetes has been discussed. Human diabetes mellitus is recognized as the result of a basic genetic defect, the nature of which is undefined. One line of evidence implicates basement membrane thickening as an early event in the patho genesis of diabetes. Further study of the formation and breakdown of the basement membrane may therefore lead to a better understanding of the genetic defect. Whether or not cyclic AMP plays a regulatory role in basement membrane synthesis is presently unknown.
Another defect recognizable in prediabetics is faulty insulin release in response to glucose infusion. This could be secondary to basement membrane thickening, but there is also evidence that the cyclic AMP mechanism may be defective. At another level, the role of cyclic AMP is more obvious: insulin deficiency leaves unopposed the actions of hormones which stimulate the production of cyclic AMP, thereby contributing to the glucose plethora and ketosis so often seen in the later stages of the disease.
Failure of Insulin Therapy to Prevent Cardiovascular Lesions in Diabetic Rats Fed an Atherogenic Diet
Authors: Wilson Robert B , Martin Julio M , Hartroft W Stanley 
Published: December 2014

In previous experiments, partially depancreatized diabetic rats, fed an atherogenic diet, consistently developed higher levels of serum cholesterol and more numerous and severe cardiovascular lesions than did similarly fed non-diabetic animals.
In the present experiment, insulin therapy prevented glucosuria from 80 to 95 per cent of the time in a group of diabetic rats fed an atherogenic diet. This therapeutic regimen was effective in promoting weight gain, improving food utilization, preventing ketonuria and, except during the first two weeks, in restricting the concentrations of serum cholesterol to within the same range as those of raline-treated nondiabetics. But this restriction in concentrations of serum cholesterol in the treated diabetics did not decrease the incidence or severity of their vascular lesions, as occurred when a comparable reduction of hyper-cholesterolemia had been effected by dietary methods.
Moreover, within groups, individual concentrations of serum cholesterol bore no relation to the severity of vascular lesions. We conclude that in this model, factors other than concentration of serum cholesterol must be important in the pathogenesis of vascular lesions.
Actions of Insulin and Growth Hormone on Collagen and Chondroitin Sulfate Synthesis in Bone Organ Cultures
Authors: Wettenhall R E H , Schwartz P L , Bornstein J 
Published: December 2014

1. The effects of insulin and growth hormone have been studied on collagen and chondroitin sulfate synthesis in bones growing in a steady state achieved by a continuous-flow bone culture system.
2. It is seen that insulin, but not growth hormone, has a significant effect on the synthesis of collagen and a marginal effect on the synthesis of chondroitin sulfate.
3. The significance of these findings is discussed.
Diabetes in a Pair of Identical Twins
Authors: Malins J M , Cassar J , Pyke D A 
Published: December 2014

We report an unusual pair of identical twins.
Jennifer B. developed diabetes at the age of four and has been on insulin ever since. She is now aged thirty and has several complications of the disease.
Shireen B., her twin, was found, immediately after appendectomy at the age of eight, to have glycosuria, and glucose tolerance was highly abnormal. She was put on insulin, but soon ceased toneed it and another glucose tolerance test after fifteen days was normal. Twenty-two years later, when thirty-seven weeks pregnant, and three and six months postpartum, she was tested again, withglucose tolerance test and insulin assay. The glucose tolerance tests were normal; the insulin response was slightly abnormal.
These findings together with those in a larger series of twins do not tend to suggest that diabetes will develop in all identical twins of diabetics.
Response of Beta Cells to Different Levels of Glucose: Fetal Pancreases Grown in Organ Culture and Subsequently Transplanted to Maternal Hosts
Authors: Hegre Orion D , Wells Lemen J , Lazarow Arnold 
Published: December 2014

Portions of pancreases from fetal rats (normal or alloxan diabetic mothers) of 19.5 days were grown in organ culture for four days on either a low glucose medium (162 to 170 mg. glucose per 100 ml.) or a high glucose medium (1,031 to 1,073 mg. glucose per 100 ml.).
Certain cultures were fixed for microscopic study. Other cultures were transplanted to the mothers at two sites: into the anterior chamber of the eye and under the capsule of the kidney. Four or ten days later, the grafts were removed, fixed and prepared for microscopic study.
Pancreases of fetuses from normal mothers had granulated beta cells at the time of explantation. When explants were grown on the high glucose medium, the beta cells became degranulated—the insulin stored at the time of explant was released from the beta cells. Subsequent transplantation of such cultures into the normal mothers restored the beta cell granulation, i.e., new insulin was synthesized and stored within the beta cells.
Pancreases of fetuses from alloxanized diabetic mothers had de granulated beta cells at the time of explantation. When these explants were grown on the low glucose medium, the beta cells developed extensive granulation representing a synthesis and storage of insulin.
Following subsequent transplantation of such cultures into the diabetic mothers, the beta cells became degranulated, i.e., release of stored insulin from the beta cells.
These observations indicate that the beta cells maintain their functional integrity (ability to store or release insulin in response to glucose) both in organ culture and when subsequently grown as grafts in maternal hosts.
Diabetes Incidence: A Two-year Follow-up of 10,000 Men in a Survey of Ischemic Heart Disease in Israel
Authors: Herman Joseph B , Medalie Jack H , Kahn Harold A , Neufeld Henry N , Riss Egon , Perlstein Tamar 
Published: December 2014

In 1963, 10,059 men aged forty years and over were examined in an I.H.D. survey and 9,711 of them were re-examined two years later. At both these examinations suspect diabetics werescreened out by a casual blood glucose value and/or a positive history of diabetes. Further information was collected on all these suspect diabetics to enable their classification into diabetic categories using similar criteria on both occasions.
Among 9,079 persons judged at risk of developing diabetes, 144 new cases of diabetes were discovered two years after the 1963 examination. The over-all two-year incidence rate for men over forty was 15.5 per thousand. Four regions of origin, Central Europe, Southeastern Europe, Israel and North Africa had incidence rates approximately equal to the over-all rate. The age adjusted incidence rate for men from Eastern Europe was lower (8.5 per 1,000) and from the Middle East higher (20.3 per 1,000) than the average.
Regulation of Insulin Release by Pancreatic Glucagon
Authors: Colwell A R , Zuckerman Leon 
Published: December 2014

In order to localize the site of its insulinogenic stimulus, glucagon was infused individually into the pancreas, liver, and peripheral circulation of normal dogs. Blood levels of insulin, glucose and nonesterified fatty acids were monitored in the femoral artery, portal and hepatic veins. The pancreatic artery infusions provoked a more rapid and marked insulin release initially than the same amount of glucagon given into the portal or femoral vein. The degree of hyperglycemia was comparable in the three groups, although the pancreatic group had more suppression of fatty acids probably related to the enhanced insulin secretion.
Intrapancreatic infusion of glucagon in amounts sufficient to release insulin always produced concomitant hyperglycemia. In comparison, small amounts of glucose administered by the same route released insulin without elevating the blood glucose level. Larger quantities of glucose, calculated to produce insulin levels similar to those attained with glucagon, provoked hyperglycemia of lesser magnitude and shorter in duration.
The effect of epinephrine on glucagon-stimulated insulin infusion. A quantity of intrapancreatic epinephrine which normally inhibits the glucose stimulus had no effect on delaying the insulin response until the amount of epinephrine was tripled.
Simultaneous measurements of insulin and glucose in the hepatic venous blood during the intrapancreatic infusion resulted in response curves similar to those found in the portal vein. Even though the hepatic venous glucose values were almost identical during the infusions at the three different sites, insulin values were two to three times lower with portal or femoral than with pancreatic infusions.
We conclude from the data that glucagon does play an independent role in the release of insulin from the pancreas, but that its effectiveness is less than glucose under normal circumstances. The glucagon stimulus is effective despite the presence of ordinary amounts of epinephrine. Since the magnitude of the insulin released from intra-portal glucagon is limited and delayed, the importance of its action as a gut factor in response to an oral glucose load is challenged.
On a Mathematical Model for the Analysis of the Glucose Tolerance Curve
Authors: Corte M Della , Romano S , Voeghelin M R , Serio M 
Published: December 2014

Three hundred and seventeen oral glucose tolerance curves have been analyzed by a mathematical model (Ackerman's model).
By application of the model to continuous venous infusion the validity of the Ackerman's hypothesis on the glucose intestinal absorption has been confirmed. The results demonstrated that the intestinal absorption rate of glucose was not statistically changed in diabetes mellitus, but decreased with age.
The period of curve T, which characterizes the glucose-insulin feed-back, the glucose fasting level and the coefficient α, which characterizes insulin removal rate independent of blood glucose and the decrease of blood glucose independent of insulin, resulted in significant differences between normal and diabetic subjects. The error involved in this method was about 7.5 per cent.
Effect of Insulin on FFA Mobilization and Ketosis in Fasting Pregnant Rats
Authors: Chernick Sidney , Novak Milan 
Published: December 2014

The concentrations of FFA and ketone bodies in plasma increased more in rats pregnant for eighteen days than in nonpregnant rats when both groups were fasted for two days. The immunoreactive insulin content of plasma was the same in fasted nonpregnant and pregnant rats whether the latter were ketotic or not. Hence, decreased circulating insulin, per se, did not appear to be the primary cause of ketosis in fasting pregnant rats. FFA mobilization was not suppressed completely by insulin in ketotic pregnant rats.
The adipose tissue of pregnant rats showed impaired metabolism of glucose and increased FFA release in vitro. Lipolysis, in the presence or absence of insulin, was greater in adipose tissue of pregnant than in that of nonpregnant rats. Ketogenesis by liver slices of pregnant rats was greater than that of nonpregnant control rats and was not reduced thirty minutes after insulin injection despite a 50 per cent lowering of the concentration of plasma FFA and ketone bodies during this time.
It is suggested that the ketosis of fasting in pregnant rats is caused by increased lipolysis in their adipose tissues and that increased FFA release is due to the absence of sufficient glucose to support re-esterification in the adipose tissues. The small effect of insulin (0.2 and 1.0 U., subcutaneously) on the plasma FFA may be due to the very low plasma glucose in fasting pregnant rats.
Effect of Streptozotocin-induced Diabetes on Pancreatic Insulin Content of the Fetus
Authors: Golob Erich K , Rishi Surendra , Becker Kenneth L , Moore Charles , Shah Narendra 
Published: December 2014

Diabetes was produced in five-day pregnant Sprague- Dawley rats by intravenous injection of 40 mg./kg. body weight of streptozotocin. Normal pregnant rats were used as controls. Pancreases of the mothers and their offsprings were extracted by acid-alcohol and the insulin measured by immunoassay using rat insulin as a standard.
Nonfasting blood sugar of the streptozotocin-treated pregnant rats was 285 ± 18 mg./100 ml. and their pancreatic insulin concentration was 5.9 ± 1 μg./gm. compared to 103 ± 3 mg./100 ml. and 44.2 μg./gm., respectively, in the normal rats.
Fetal pancreases of streptozotocin-induced diabetic pregnant rats and normal animals were obtained on Days 18, 19, and 21 of gestation, and on Day 4 after birth. The pancreatic insulin concentration of fetuses of diabetic mothers rapidly and progressively increased from 8.0 ± 0.9 μg./gm. on Day 18 to a peak of 63.0 ± 9.0 /μg./gm. on Day 21. On Day 4 after birth, the value was 312 ± 109 μg./gm. The total pancreatic insulin content also progressively increased to a prenatal peak of 0.84 ± 0.15 μg. on Day 21. The pancreatic insulin concentration of fetuses of normal mothers was not significantly different from those of diabetic mothers. There was no correlation between the elevation of maternal blood sugar and the insulin concentration of the fetal pancreas. The total pancreatic insulin content of fetuses of diabetic rats was less than those offspring of the normal rats on Day 18 and Day 4 after birth, but was not significantly different on Days 19 and 21. The lower insulin content found in fourday-old rats born of diabetic animals was probably related to their inability to obtain adequate nourishment from their very sick mothers.
Evidence for a Feedback Inhibition of Insulin on Insulin Secretion in the Isolated, Perfused Canine Pancreas
Authors: Iversen Johan , Miles David W 
Published: December 2014

An isolated in vitro canine pancreas per fusion preparation is described which is suitable for prolonged (five hours) study of insulin secretion. The preparation remains in good condition throughout the experimental period judged by various parameters.
Feedback inhibition of insulin on insulin secretion was studied in the preparation. Experiments were performed at different concentrations of glucose in the influx medium. At 150 mg. per cent of glucose a considerable reduction of the insulin secretion was obtained when exogenous porcine insulin was added to the influx medium in concentrations from 180 μU./ml. to 420 μU./ml.
In eight experiments where the exogenous insulin concentration in the influx medium was equal to or exceeded pre-inhibition efflux values the obtained insulin inhibition amounted to 25-78 per cent of the pre-inhibition values. In one of the eight experiments the exogenous insulin concentration was less than the pre-inhibition value; however, the same effect was obtained.
A feedback mechanism of insulin on insulin secretion from the beta cell has thus been demonstrated at levels of perfusate insulin which occur in vivo.
Effect of Diabetes on the Biosynthesis of the Renal Glomerular Basement Membrane: Studies on the Glucosyltransferase
Authors: Spiro Robert G , Spiro Mary Jane 
Published: December 2014

Kidney glucosyltransferase (UDP-glucose: galactosylhydroxylysine-basement membrane glucosyltransferase), which is involved in the synthesis of the hydroxylsine-linked disaccharide units of glomerular basement membrane, has been measured in the renal cortices of normal and alloxan diabetic rats. The level of this enzyme in diabetic kidneys was found to be significantly elevated over that of age-matched controls, expressed either as specific or total activity, at all times studied (one to five months). However the difference between the normal and diabetic animalsincreased with the duration of the disease. When short-term diabetics were treated with insulin, the level of the glucosyltransferase could be restored to normal. Insulin treatment of long-term diabetic animals, which were more difficult to control, brought the enzyme level close to normal but did not completely restore it.
The glucosyltransferase activity in several other tissues of the alloxan diabetic rat, including lung, liver, testes, spleen, and uterus, did not show any significant elevation over that of the normal.
Measurement in kidney of a glycosyltransferase (UDP-galactose :N-acetylglucosamine-glycoprotein galactosyltransferase) involved in the synthesis of a different type of carbohydrate unit did not show the marked elevation noted for the glucosyltransferase.
It is believed that the insulin-reversible glucosyltransferase elevation of the diabetic renal cortex reflects the increased basement membrane synthesis occurring in this tissue and indicates that this process is directly or indirectly under the control of this hormone.
Cephalic Phase of Insulin Secretion in Obese Adolescents
Authors: Parra-Covarrubias Adalberto , Rivera-Rodriguez Irene , Almaraz-Ugalde Arturo 
Published: December 2014

The influence of a visual and olfactory meal stimulus on plasma insulin, free fatty acids and glucose levels, was studied in six obese, nondiabetic young persons.
There was a significant increase in plasma immunoreactive insulin with a simultaneous decrease in plasma free fatty acids without demonstrable changes in plasma glucose. The observed rise in plasma immunoreactive insulin most probably is reflex in nature. However, all levels of the nervous system including cerebral cortex, reticular formation and hypothalamus, may play different roles in the facilitation or inhibition of such reflex. The participation of one or several of the gastrointestinal hormones, such as secretin or gastrin, could explain the delayed rise in plasma insulin. Dietary habits, appetite, palatability of the offered meal and a relaxed and tranquil patient seem to be essential factors to be taken into consideration, if success is to be achieved in this type of experimental study.
Diabetic Retinopathy: New Vessels Arising from the Optic Disc: I. Grading System and Natural History
Authors: Kohner E M , Panisset A , Cheng H , Fraser T R 
Published: December 2014

1. A grading method for new vessels arising from the optic disc is described. The grading system has been used to study the natural history of new vessels in forty-four eyes of thirty diabetic patients.
2. While some eyes showed considerable changes, the mean progression of new vessels in the entire group was slight and only reached one grade in four years.
3. The most striking feature of the study was the number of eyes which could not be fully assessed at different times during the follow-up period. Eyes became unassessable because of vitreous hemorrhage or retinitis proliferans. These increased from 18 per cent at six months to 66 per cent at four years. Both of these were more common when higher grading values of new vessels were reached.
4. The visual acuity deteriorated in twenty-five eyes. In nineteen of the eyes the deterioration was three lines or more; fifteen eyes became blind. The commonest cause for visual deterioration was vitreous hemorrhage.
Influence of Nutritional Factors on Prevalence of Diabetes
Authors: West Kelly M , Kalbfleisch John M 
Published: December 2014

Twelve age-matched populations of eleven countries were tested by standardized methods to determine associations between prevalence of hyperglycemia and certain epidemiologic variables, including several nutritional factors. There were great differences among some of these populations in socioeconomic status, diet, adiposity, and race. Environmental and demographic circumstances varied widely and prevalence of diabetes differed as much as ten-fold. There was in general a positive association between prevalence of diabetes and dietary intake of fat and of sugar, and a negative association between prevalence of diabetes and total carbohydrate consumption; but some inconsistencies in these associations suggested that they may have been partly or completely coincidental. Prevalence of diabetes correlated well with serum cholesterol levels, both among and within populations. Thejnost impressive and consistent association in these studies was between prevalence of diabetes and fatness (as estimated by weight in relation to height). Both within and among countries and races, this association was observed to a high degree. Interracial differences in prevalence of diabetes were small when racial groups were matched for adiposity.
In a group of 1,645 subjects from the general population of Central America, those with abnormal glucose tolerance had a substantially higher prevalence of electrocardiographic abnormalities than those with normal tolerance.
Cellular Localization of Gastrin in the Human Pancreas
Authors: Greider Marie H , McGuigan James E 
Published: December 2014

Cryostat-cut sections of unfixed and formalin-fixed human pancreata obtained at autopsy were stained by the direct method with fluoresceinated antibodies to human gastrin I. The cytoplasm of a small population of cells in the islets of Langerhans exhibited a bright yellow-green fluorescence. Specificity of the inimunochemical reaction was indicated by a decrease in intensity of stain after preincubation of the fluoresceinated antibody with gastrin and after pretreating the section with nonfluoresceinated antibody-preparation. Immunological cross reactivity with cholecystokinin-pancreozymin was excluded by use of highly specific fluoresceinlabelled antibodies to human gastrin I which exhibit no binding of cholecystokinin-pancreozymin.
The presence of immunoreactive gastrin in the human pancreas was also demonstrated by radioimmunoassay measurements of pancreatic tissue extracts.
The gastrin-containing cells were selectively stained by the Hellerstrom-Hellman method, indicating that the gastrin cell of the pancreatic islet is the classical delta cell of Bloom (or A1 cell of Hellerstrom and Hellman).