bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth of Rabbit Aortic Smooth-Muscle Cells Cultured in Media Containing Diabetic and Hyperlipemic Serum
Authors: Ledet Thomas , Dzoga Katti Fischer , Wissler Rober W 
Published: September 2013

Smooth-muscle cell cultures were grown from thoracic aortas of normal and diabetic rabbits. The effect of diabetic rabbit serum on the growth of these cultures was studied both in the first, rapid-growth phase and the following, more “stationary” phase of growth. Control experiments were carried out on normal sera to which glucose had been added. The concentrations of cholesterol, phospholipid, and triglyceride were same in both normal and diabetic sera.
Media containing diabetic serum stimulated the growth of cultures significantly in both phases (2p &lt; 0.01). This occurred in experiments utilizing cells from normal as well as from diabetic rabbits. Control media containing normal serum with added glucose had no such effect. The growth-promoting effects of diabetic serum and of hyperlipemic serum from nondiabetic rabbits were of the same order of magnitude.
Autoradiographic studies showed that the number of 3H-thymidine-labeled cells increased significantly after culture in diabetic serum (2p &lt; 0.005).
Cells cultured from the very beginning in diabetic serum or normal serum with added glucose were significantly larger than cells grown in control serum (2p &lt; 0.05 and 2p &lt; 0.01, respectively). Cells grown in hyperlipemic serum were significantly smaller than those grown in normal serum (2p &lt; 0.01).
These results indicate that diabetic serum contains a factor or factors that stimulate the arterial medial cell to excessive growth. This factor is not glucose, insulin, or lipid. The results may be of relevance for the understanding of human diabetic macroangiopathy.
Effect of Somatostatin on Blood Sugar, Plasma Growth Hormone, and Glucagon Levels in Diabetic Children
Authors: Guercio M J Del , Natale B di , Gargantini L , Garlaschi C , Chiumello G 
Published: September 2013

In nine children with clinically overt insulin-dependent diabetes mellitus the authors injected cyclic somatostatin (3 mug./kg. bolus, followed by infusion of 13 mug./kg. in 60 minutes) and measured blood glucose, plasma growth hormone, and glucagon concentrations throughout the infusion. The rapid administration produced no significant changes of these parameters. With the prolonged infusion there was a significant reduction of blood glucose from a mean of 148 ± 19.7 to a mean of 88.5 ± 18.1 mg./100 ml. (P &lt; 0.005) and of plasma glucagon from a basal mean of 33.3 ± 2.4 to a minimum mean of 22.1 ± 1.7 pg./ml. (P &lt; 0.01). There was a statistically significant correlation between the two parameters (0.01 &lt; P &lt; 0.05). Plasma GH values also diminished during the infusion, but the reduction was not statistically significant.
These results show that somatostatin lowers blood glucose concentrations as a secondary effect of inhibition of glucagon secretion. Somatostatin is not suitable for therapy in diabetes. We speculate that a similar substance with a more prolonged and specific action on glucagon might prove of practical value in the treatment of diabetes mellitus.
Carbohydrate Metabolism and Capillary Basement-membrane Thickness in Children: II. Longitudinal Studies
Authors: Sheikholislam Bagher M , Irias Julian J , Lowrey George H , Lin Hung-Jung 
Published: September 2013

Longitudinal biochemical and histologic studies were carried out in 11 children receiving oral hypoglycemic agents. There were five “suspected” diabetics (with evidence of glucose intolerance but without repeated fasting hyperglycemia) and six diabetics.
Mean fasting plasma glucose (FPG) values showed no significant change during treatment with phenformin alone. The mean FPG decreased significantly within six to 10 weeks after addition of tolazamide to the regimen, but the decrease was not sustained during long-term observation (seven months to four years). Glucose disappearance rate (K) generally increased as FPG decreased, but the number of observations was smaller, and mean values showed no significant change. Mean values for fasting plasma insulin and for peak insulin response to intravenously administered glucose did not change significantly.
Changes in capillary basement-membrane thickness (BMT) were found to be statistically significant in a number of individual instances. Decreasing BMTs were associated with increasing Ks and vice versa. A similar trend was apparent among other patients, in whom individual changes in BMT were not statistically significant. The pooled data were therefore subjected to chi-square analysis; K and average BMT were found to change in opposite directions (P &lt; 0.001); a similar relationship held for K and minimum BMT (P &lt; 0.05). But K and BMT did not correlate well as regards magnitude of change. Influences of phenformin and tolazamide on these changes could not be evaluated.
Both BMT and K may be influenced by many complex variables, but the present findings indicate that glucose tolerance and BMT have a close interdependence.
Vascular Lesions Associated with Impotence in Diabetic and Nondiabetic Arterial Occlusive Disease
Authors: Herman Aryeh , Adar Raphael , Rubinstein Zalman 
Published: September 2013

Translumbar aortographies performed in 91 patients for limiting leg ischemia were reviewed, and stenosis was graded by points from one (normal vessel) to five (complete occlusion) for each vessel. Of 62 nondiabetic patients, 18 (29 per cent) were impotent, while of 29 diabetics, 17 (58.6 per cent) were impotent (p &lt; 0.01). Significantly greater stenosis (p &lt; 0.005) was found in the internal pudendal arteries of impotent patients when compared statistically with potent patients. This was true for the group as a whole, for diabetics and nondiabetics, and for patients over 50 years old both with and without diabetes. There was no significant difference in the extent of stenosis of the iliac arteries (common and internal) between potent and impotent patients. There was also no significant difference in the pattern of stenosis between diabetic and nondiabetic patients in the group as a whole and also in the potent and impotent subgroups analyzed separately. Neither diminished femoral pulses nor aortographic evidence of external iliac and common femoral arterial stenosis correlated significantly with impotence.
These observations indicate that vascular lesions are as important in diabetics as in nondiabetics in the genesis of impotence. Clinical implications regarding diagnostic investigations and treatment are discussed.
Influence of Maturity-onset Diabetes on Splanchnic Glucose Balance After Oral Glucose Ingestion
Authors: Felig Philip , Wahren John , Hendler Rosa 
Published: September 2013

To determine the extent to which altered splanchnic glucose balance contributes to postprandial hyperglycemie in diabetes, splanchnic glucose exchange was determined in seven maturity-onset diabetics and 10 healthy control subjects in the basal state and for three hours following oral ingestion of 100 gm. of glucose.
In the basal fasting state, arterial glucose levels in the diabetics (153±24 mg./100 ml.) were 75 to 80 mg./100 ml. higher than in controls while splanchnic glucose output was similar in the two groups (132 to 145 mg. per minute). Following glucose ingestion, arterial glucose concentration in the diabetics rose to peak levels (295 ±35 mg./100 ml.) that were 55 per cent higher than in controls and remained 100 to 125 mg./100 ml. above basal levels and 150 to 200 mg./100 ml. above control levels three hours after glucose. Splanchnic glucose output rose rapidly in the diabetics to values four times the basal rate at 15 to 30 minutes after glucose feeding and remained 60 per cent or more above basal levels throughout the three-hour period. In contrast, in the controls following a similar early rise, splanchnic glucose output returned to basal levels by 90 minutes. As a consequence, total splanchnic glucose output over three hours in the diabetics (53±4 gm.) was 33 per cent greater than in controls. In addition, the increment in splanchnic glucose output above basal levels in the diabetics (30±5 gm.) was 100 per cent greater than in controls and could account for 75 per cent of the augmented glucose accumulation in body fluids observed at three hours.
It is concluded that in maturity-onset diabetics (1) net splanchnic glucose output is increased after glucose ingestion, suggesting that a greater proportion of an oral glucose load enters the systemic circulation than in healthy controls; (2) failure of splanchnic glucose retention is the major factor responsible for postprandial hyperglycémie in maturity-onset diabetes.
Glucose-stimulated 45Ca Uptake in Isolated Rat Islets
Authors: Frankel Barbara J , Kromhout John A , Landahl Herbert D , Grodsky Gerold M 
Published: September 2013

Net 45Ca uptake (in excess of the extracellular 3H-sucrose space) and insulin release were measured under low (2 mM) and high (20 mM) glucose conditions in collagenase-isolated rat islets. 45Ca uptake curves were mathematically fitted and subjected to compartmental analysis.
Within the first 60 seconds after addition of trace 45Ca, islets showed a similar rapid uptake of 45Ca regardless of the glucose concentration or length of time of prior exposure to glucose. Net 45Ca uptake continued to increase for 30-60 minutes, and the islets in high glucose showed approximately twofold greater maximum uptake than islets in low glucose. Islets preincubated in low glucose and then incubated in high glucose showed a 5-15-minute delay in net 45Ca uptake as compared with islets that had been preincubated in high glucose.
Insulin release was detectable by 10 minutes of incubation with high glucose.
Mathematical modeling of the low- and high-glucose net 45Ca uptake curves suggests that there are at least two calcium “compartments” within the β-cell. One compartment is small, rapidly filled, and insensitive to glucose, while the other, larger compartment, is slowly filled and fills to a much greater extent in the presence of high glucose. A major proportion of the glucose-stimulated uptake is at the level of influx.
Low Density Lipoprotein Receptor Activity in Fibroblasts Cultured from Diabetic Donors
Authors: Chait Alan , Bierman Edwin L , Albers John J 
Published: September 2013

Low density lipoprotein (LDL) receptor activity was evaluated in cultured skin fibroblasts from diabetics and nondiabetic controls to evaluate whether intrinsic abnormalities of the LDL pathway exist, which might account for the premature atherosclerosis associated with diabetes mellitus. LDL receptors did not differ between cells grown from 16 diabetics (7 insulin-dependent, 9 non-insulin-dependent) or from 16 nondiabetic controls. An inverse relationship between LDL receptor activity and cell density was observed (y = 1.35 × −1.22, r = 0.90, P &lt; 0.001), which appeared the same for diabetic and nondiabetic cells. Normalized values for LDL degradation by diabetic and nondiabetic cell strains were 1.52 ± 0.42% of added LDL/106 cells and 1.34 ± 0.28, respectively (P = NS). The kinetics of the LDL receptor also appeared to be the same in cells derived from a diabetic and a nondiabetic donor. LDL receptor activity in diabetic cells increased appropriately in response to physiologic concentrations of insulin in the incubation medium.
Thus, LDL receptor activity appears to be normal in diabetic cell strains. Therefore, these results do not support the possibility that alterations in the LDL pathway contribute to the accelerated atherosclerosis associated with diabetes.
A Study of Glucagonomas by Light and Electron Microscopy and Immunofluorescence
Authors: Bordi Cesare , Ravazzola Mariella , Baetens Dany , Gorden Phillip , Unger Roger H , Orci Lelio 
Published: September 2013

Five tumors associated with the complete glucagonoma syndrome, as well as a series of glucagon-cell adenomas from three patients without this syndrome, were investigated by light and electron microscopy and by immunofluorescence.
All tumors associated with the syndrome were large, from 3 to 35 cm along the major axis, and three of them were proved to be malignant. No common histologic arrangement of tumor cells was apparent for the five neoplasms examined. Immunofluorescent staining for glucagon and glicentin was carried out: while most cells were negative, a varying number of scattered cells were positive with both antisera in all tumors except one; three tumors contained more glicentin- than glucagon-immunoreactive cells. Moreover, three tumors were multihormonal, with cells positive for pancreatic polypeptide and/or insulin. Ultrastruc-turally, the secretory granules of cells from these tumors were not typical of those found in A-cells from adult human islets.
The glucagon-cell tumors from patients without the syndrome were benign, usually multiple, and were small, with diameters from 0.5 mm to 1 cm. In most cases, the cells from these neoplasms arranged in a characteristic pattern (ribbonlike or “gyriform”). In most tumors, the majority of cells showed both glucagon and glicentin immunofluorescence and the ultra-structural appearance of their secretory granules was similar to that of normal islet A-cells. From the morphologic point of view, therefore, cells from tumors not associated with the glucagonoma syndrome resemble normal glucagon cells more closely than those from tumors associated with the syndrome.
Reduced Monoamine Oxidase Activity in Blood Platelets from Insulin-dependent Diabetic Subjects
Authors: Mosnaim Aron D , Wolf Marion E , Huprikar Shankar , Singh Sant P , Zeller E Albert 
Published: September 2013

Insulin-dependent diabetics show a significant reduction in blood platelets' monoamine oxidase (MAO) activity when compared with age-matched and sex-matched controls. This does not appear to be the case for diabetics either on diet control or receiving oral hypoglycemic drugs.
The important role of this enzyme in the regulation of the circulating levels of a number of monoamines known to have an inhibitory effect on insulin secretion may indicate the possible inclusion of the MAO/monoamine system in the pathophysiology of diabetes. The possibility of using platelets' MAO activity as a biologic marker for a subgroup of insulin-dependent diabetics is also discussed.
Synthesis and Accumulation of Triglycerides in Liver of Diabetic Rats: Effects of Insulin Treatment
Authors: Murthy Veeraraghavan K , Shipp Joseph C 
Published: September 2013

The relationship between the severity of diabetes and the hepatic accumulation of triglycerides in the streptozotocin-diabetic rat was studied. A consistent increase in hepatic triglyceride content was observed only in the ketotic diabetic state. Insulin treatment of the ketotic diabetic rat resulted in the reversal of increased plasma concentrations of glucose, free fatty acids, β-hydroxybutyric acid, and triglycerides to those observed in nondiabetic controls. Insulin treatment of the ketotic rats, however, did not completely eliminate the accumulation of the hepatic triglycerides.
To determine whether increased triglyceride synthesis was a contributory factor to the hepatic triglyceride accumulation, triglyceride synthesis was studied in vitro using nuclear-free homogenates of liver. Triglyceride synthesis increased in ketotic diabetes. Insulin treatment of the ketotic rats partially reversed the increased diglyceride synthesis observed in ketosis but had no effect on the accelerated triglyceride synthesis. The effects of ketotic diabetes and insulin treatment of the diabetic rat on the activities of two key enzymes of the triglyceride biosynthetic pathway were examined next. The maximal velocities (Vmax) of liver-soluble phosphatidate phosphohydrolase and of microsomal diglyceride acyltransferase increased in ketosis. Insulin treatment of the diabetic rats reverted the activity of these two enzymes to control values.
The results of our study demonstrate that hepatic triglyceride synthesis in ketotic rats accelerates at a time when hepatic triglyceride content increases, the increased synthesis of triglycerides was associated with increases in the activities of two key enzymes of triglyceride biosynthesis. There was a correlation between hepatic triglyceride content and triglyceride synthesis in control, ketotic diabetic, and insulin-treatedrats. These observations suggest a physiologic role for the observed changes in the accumulation of hepatic triglycerides in ketotic diabetes.
Time Dependence of the Glycogenic Effect of Insulin in Cultured Fetal Hepatocytes
Authors: Plas C , Menuelle P , Moncany M L J , Fulchignoni-Lataud M C 
Published: September 2013

Primary cultures of rat fetal hepatocytes were used to study the effect of insulin on glycogenesis during 24 h. Measurements of both glycogen content and 14C-glucose incorporation into glycogen gave similar results. A clear stimulatory insulin effect was observed within one hour, reaching a maximum after three hours. However, from 4 to 12 h, the effect declined strongly and then disappeared. Thereafter, it reappeared but to a lesser extent. These striking variations were not caused by a lack of active insulin in the medium or by any amplification of time variations in hepatocyte basal glycogenic capacity. They were induced by the hormone itself as a function of time of insulin presence at the hepatocyte level. Therefore, the effect of insulin is time dependent.
The transient cessation in the stimulatory effect of insulin on net glycogenesis limits the total amount of glycogen stored and permits a more progressive glycogen accumulation. It is not yet clear whether this cessation is a result of a decrease in the insulin-stimulated glycogen synthesis, or an increase of glycogen breakdown, or both; but we showed that it does not require prior maximal stimulation of glycogenesis. After four hours of incubation with varying doses of insulin, a dosedependent decrease in the insulin glycogenic effect of a second maximal dose of hormone was observed, whereas glucagon-induced glycogenolysis was unchanged. The characteristics of the time dependence of the insulin effect suggest that it may play a regulatory role in fetal hepatocytes.
Insulin-degrading Activity of Plasma Membranes from Rat Skeletal Muscle: Its Isolation, Characterization, and Biologic Significance
Authors: Yokono Koichi , Imamura Yoshimichi , Sakai Hideyo , Baba Shigeaki 
Published: September 2013

We isolated the plasma membrane from rat skeletal muscle without using drastic procedures such as extraction by salts or other agents. As a result of the purity of our preparations, evaluated by enzymatic markers, lipid composition, 125l-insulin specific binding, and morphologic examinations, we were able to use the plasma membrane to study insulin degradation.
Isolated plasma membranes were capable of degrading insulin, but 95% of total degrading activity was found in the cytosol fraction. The membranes proteolytically degraded the hormone with a high degree of specificity and a pH optimum of 7.0. The extent of degradation depended on time, temperature, and protein concentration. The apparent Km for insulin was 1.7 × 10−7 M. N-ethylmaleimide (NEM) and p-chloromercuribenzoate (PCMB) markedly inhibited insulin degradation by membranes, whereas glutathione (GSH) and dithíothreitol (DTT) were stimulatory. These characteristics of insulin-degrading activity in the plasma membrane (membrane-IDE) were similar to those of the partially purified insulin-degrading enzyme from the cytosol fraction (cytosol-IDE).
To clarify the biologic significance of IDE, we examined the cytosol- and membrane-IDE activities under various conditions in rats grouped as follows: fed, fasted for 1 day, fasted for 3 days, refed, refed + actinomycin D, diabetic, and hyperinsulinemic (insulinoma). A positive correlation with a high coefficient (r = 0.674, P &lt; 0.001) was demonstrated between cytosol-IDE and the plasma insulin concentration but not between membrane-IDE and insulin levels. While actinomycin D had no effect on membrane-IDE levels, it abolished the insulin-mediated rise in cytosol-IDE activity, suggesting that the latter was dependent on RNA synthesis.
Perifusion and Culture of Human Fetal Pancreas
Authors: Maitland Janice E , Parry David G , Turtle John R 
Published: September 2013

Human fetal pancreas has been obtained, after the therapeutic termination of pregnancy with prostaglandin F2α. Pancreatic explants were studied in a perifusion system and maintained in organ culture for up to 3 wk. Insulin biosynthesis was stimulated by glucose; however, the incorporation of 3H-L-leucine into proinsulin was surprisingly high (52% after 3 h) vs. insulin (48%), which suggests a possible block in the conversion of proinsulin to insulin. Insulin secretion was stimulated during perifusion with 19.3 mM glucose (1.6× prestimulation level), 1.5 μM glucagon (2.4), 5 mM leucine (2.4), 10 mM arginine (2.7), and 10 mM theophylline (10.0).
Insulin biosynthesis and secretion were maintained in organ culture. After 12 days there was a 3.4-fold increase in insulin secretion in the presence of 22 mM glucose compared with 5.5 mM glucose, and the explant insulin content rose in the presence of high glucose levels by 89%. The acute insulin secretory response to 10 mM theophylline was maintained after culture.
These studies suggest that human fetal pancreas should be considered as a potential source of donor tissue for pancreas transplantation in human diabetes.
Decreased Insulin Binding and Degradation Associated with Depressed Intracellular ATP Content
Authors: Draznin Boris , Solomons Clive C , Emler Carol A , Schalch Don S , Sussman Karl E 
Published: September 2013

The effect of metabolic inhibitors, 2,4-dinitrophenol (DNP) and NaF, on insulin binding and degradation has been studied in cultured Buffalo rat liver (BRL) cells. In control studies, 1.8 fmol of 125I-insulin binds to 1.2 × 106 cells, possessing approximately 40,000 receptor sites per cell with binding affinity of 5.52 × 10−8 M. When the cells were preincubated with increasing concentrations of either DNP or NaF, a dose- and time-dependent decrease in both insulin binding and degradation was observed. The total amount of 125I-insulin bound to BRL cells preincubated with metabolic inhibitors was reduced to 1.2 fmol per 1.2 × 106 cells. The point of ½ B max was achieved in the presence of 50 ng/ml of native insulin, 1.7 times that of the control level. The number of receptor sites was unaffected by either DNP or NaF, but an average affinity profile revealed a decrease in the affinity of the ATP-depleted cells for insulin (KD : 7.31 × 10 −8 M and 7.06 × 10−8 M in DNP- and NaF-treated cells, respectively). The decrease in insulin binding and degradation following the exposure of the BRL cells to the metabolic inhibitors was associated with a 20% reduction in intracellular ATP and adenylate energy charge. DNP and NaF did not affect the equilibrium constant for the myokinase catalyzed reaction and the intracellular concentration of hypoxanthine was stable, confirming the integrity of the cells during the experiments.
It is suggested that ATP levels must remain intact to maintain normal insulin receptor affinity. Furthermore, the rate of insulin degradation by ATP-depleted cells is slower than that of intact cells. It is conceivable that the depression of insulin degradation by partially ATP-depleted cells results from either diminished binding or decreased endocytosis and lysosomal activity, all of which appear to be energy dependent.