bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin Secretion Studied in the Perfused Rat Pancreas: II. Effect of Glucose, Glucagon, 3'5' Adenosine Monophosphate, Theophylline, Imidazole and Phenoxybenzamine; Their Interaction with Diazoxide
Authors: Basabe J C , Lopez N L , Viktora J K , Wolff F W , McNeal B , Mongelli C , WcInhardt K , Baukal A 
Published: December 2014

This communication reports studies dealing with the action of glucagon, theophylline, cyclic adenosine monophosphate (3′5′.AMP) and phenoxybenzamine on insulin secretion, and their possible interaction with glucose and diazoxide.
Diazoxide inhibited both phases of insulin secretion produced by glucose. This blocking action was suppressed when the alpha-blocking phenoxybenzamine was present.
Glucagon produced a uniform pattern of insulin secretion when perfused alone. A one-minute pulse of 3′5′.AMP produced a sharp peak of insulin secretion. Neither glucagon nor 3′5′.AMP effects were inhibited by diazoxide.
Theophylline did not increase the basal insulin-secretion. However, when perfused together with glucose, theophylline stimulated additional insulin secretion, significantly higher than that produced by glucose alone.
When combinations of glucagon plus glucose, 3′5′.AMP plus glucose and theophylline plus glucose, were perfused, diazoxide blocked the secretion of insulin stimulated by glucose, but not that produced by glucagon, 3′5′.AMP or theophylline. This suggests that glucagon, 3′5′.AMP and theophylline stimulate insulin secretion by actingon mechanismsdifferent from the ones stimulated by glucose
Capillary Blood Sugar Values in Children During the Oral Cortisone-Primed Glucose Tolerance Test
Authors: Cole Harold S , Bilder Joan H , Epel Rosa 
Published: December 2014

Three-hour oral cortisone-primed glucose tolerance tests were performed on a total of 113 children in three age groups; 1½ to less than 4 yrs., 4 yrs. to less than 8 yrs., and 8 to 12 yrs. of age. All children had negative family histories for diabetes, were in good health, and had recent normal oral glucose tolerance tests. A capillary blood micro-technic for blood sugar was used. Oral glucose was administered according to age and weight. The total cortisone dosage was 280 mg. per M2 given in two equally divided doses eight-and-one-half and two hours before the testing.
It is suggested that the blood sugar values for the 1½ to less than 4 yrs. age group be considered separately because of significant differences from the other age groups. The values for the ± 2 standard deviation range for boys and girls from 4 to 12 yrs. of age were: fasting (54.4–114.0 mg./100 ml.); 30 min. (96.1–202.9 mg./100 ml.); 60 min. (74.7–202.3 mg./100 ml.); 90 min. (72.5–169.3 mg./100 ml.); 120 min. (65.8–157.4 mg./100 ml.) ; 180 min. (49.6–122.4 mg./100 ml.).
Studies of Adenosine and Dibutyryl Adenosine 3'5'-Monophosphoric Acid on the Isolated Fat Cell
Authors: Solomon Solomon S , Kitabchi Abbas E 
Published: December 2014

The action of adenosine 3',5'-monophosphate (c-AMP) and N6, O2'-dibutyryl adenosine 3',5'-monophosphate (dc- AMP) was studied in isolated rat adipocytes using parameters of glucose oxidation and lipolysis. Whereas c-AMP stimulated the conversion of glucose-U-C-14 or glucose-1-C-14 to C-14-O2, dc-AMP inhibited C-14-O2 production below the baseline in each case. Both N6-monobutyryl adenosine 3',5'-monophosphate (N6 mbc-AMP) and O2'-monobutyryl-adenosine 3',5'-monophosphate (O2'-mbc-AMP) stimulated C-14-O2 production from glucose-U-C-14. Only N6-mbc-AMP, however, was significantly lipolytic. When glucose-6-C-14 was utilized as the substrate, both c-AMP and dc-AMP stimulated its conversion to C-14-O2.
Dibutyryl cyclic AMP antagonized the action of insulin and proinsulin on glucose-U-C-14 oxidation in the isolated fat cell by an apparent competitive mechanism. Paradoxically, insulin potentiated C-14-O2 production from glucose-6-C-14. in the presence of 1.0 mM dc-AMP. C-AMP exhibited no such response.
It is concluded that under the experimental conditions described, (1) c-AMP and dc-AMP exhibit divergent effects with regard to glucose oxidation; (2) by the use of glucose-U-C-14 and glucose-l-C-14, dc-AMP competitively inhibits the action of insulin or proinsulin on glucose oxidation; (3) insulin synergistically stimulates C-14-O2 production from glucose-6-C-14, in the presence of dc-AMP; and (4) both N6- and O2'-butyrate moieties are necessary for the inhibitory effect on glucose oxidation observed with dc-AMP.
Fine Structure of the Endocrine Pancreas in Newborn Rodents
Authors: Boquist Lennart 
Published: December 2014

The pancreases of one to ten day old mice, Chinese hamters and Mongolian gerbils were examined by electron microscopy. Any essential species or sex differences were not recorded. In the ductules there were endocrine cells, sometimes reaching the lumen. Endocrine cells were also seen in buds on the ductules. Mitosis occurred in acinar, centroacinar, ductule, A—, B—, and capillary endothelial cells. The ductule cells exhibited cilia and signs of ceritriole replication. The various islet parenchymal cell types could be differentiated in all animals. Other findings were perinuclear fibril bundles, structural variation of the secretory granules, dilated intercellular spaces and signs of emiocytosis.
The results indicate that in the species investigated, new formation of endocrine cells occurs in the neonatal period both by proliferation and development of endocrine cells from the ductules and by mitotic division of the islet parenchymal cells. No morphologically detectable lesions were found in the islets of newborns of the Chinese hamster which has a hereditary trait for the development of diabetes mellitus.
Glucose Metabolism and Responsiveness to Bovine Insulin by Adipose Tissue from Three Mammalian Species
Authors: Di Girolamo Mario , Mendlinger Sheldon 
Published: December 2014

The rate and pattern of glucose metabolism by slices of epididymal adipose tissue from ad libitum-fed rats, hamsters and guinea pigs were studied in an in vitro incubation, at three stages of development during the first year of the animals' lives. The results were expressed on the basis of fat cell number and in relation to the fat cell size. The responsiveness of the adipose cells to the glucose-transport stimulating effect of bovine insulin was determined in relation to the age of the animals and to the adipocyte volume. The data indicate that the amounts of basal glucose metabolized to [CO2 + triglyceride] per fat cell remained relatively constant in each of the three species, even though the fat cell volumes varied markedly. In concomitance with fat cell enlargement, the pattern of glucose metabolism exhibited a progressive change, with reduction in the proportions of glucose converted to CO2 and glyceride-fatty acid and a significant increase in that of glucose converted to glyceride-glycerol.
The effect of bovine insulin in stimulating glucose transport and metabolism varied from species to species being greatest in the rat and smallest in the guinea pig fat cells. In each species, the magnitude of the response to bovine insulin was found to be decreased as the fat cells enlarged with age and ad libitum feeding of the animals. The guinea pig differed from the other two species in the limited capacity of the fat cells to enlarge during the period of observations. In spite of the small fat cell size, the response of guinea pig fat cells to bovine insulin was minimal. During growth and development of the animals, fat cell number, baseline rate of glucose metabolism and responsiveness to insulin contribute to the over-all glucose metabolism by the epididymal fat pads; in the guinea pig, the contribution of fat cell number appeared to be quantitatively more important than the stimulatory effect of insulin.
Effect of Blood Sugar Control on the Accumulation of Sorbitol and Fructose in Nervous Tissues
Authors: Ward J D , Baker R W R , Davis Barbara H 
Published: December 2014

Some products of the sorbitol metabolic pathway of glucose were extracted from peripheral nerves and spinal cords of rats, identified, and measured. Within a few days after a diabetic state was induced with streptozotocin, glucose, sorbitol, and fructose in nerve and cord had risen sharply as blood glucose increased. These levels were partially controlled when the blood sugar was restricted by insulin, but they increased rapidly when the insulin was withheld. Withdrawal of treatment resulted in a much greater rise of the fructose in the nervous system in animals that had been diabetic for six weeks before institution of treatment with insulin than in animals treated from induction. When phen-formin was used as a controlling agent in place of insulin, accumulation of glucose and fructose in the nervous system was enhanced, whereas fructose was found to decrease when tolbutamide was used.
Earlier workers have shown that the sorbitol pathway seems to be associated with the Schwann cell and that dysfunction of this cell leads to segmental demyelination. We find that accumulation in nerves of the products of the sorbitol pathway may be minimized when blood sugar is controlled; since we have evidence that in human beings with diabetes good control improves the state of myelination of already damaged nerves, it is postulated that herein lies the mechanism whereby control of diabetes is likely to lead to a reduction in the incidence of nerve damage.
The Prediabetic State, Its Nature and Consequences—A Look Toward the Future
Authors: Cerasi Erol , Luft Rolf 
Published: December 2014

The prediabetic state is characterized by normal glucose tolerance but decreased insulin secretion following glucose stimulation. In spite of our earlier beliefs, this state is not always devoid of metabolic consequences. Thus, the disappearance rate of intravenously administered glucose (k-value), although within the normal range, is significantly lower than in the control group. In a few prediabetics the regulation of hepatic glucose output resembles that of diabetics. In some, the lipolytic response to physical exercise is increased to the extent found in manifest diabetes. Furthermore, prediabetic mothers may give birth to children with diabetic fetopathy. Many of the newborns of these women show high k-values as do children of diabetic women.
The decreased insulin output of prediabetics and mild diabetics is probably due to a decreased sensitivity for glucose of a specific receptor of the beta cells of the pancreas. This suggestion is supported by the finding that both prediabetics and mild diabetics can release normal amounts of insulin provided blood glucose is raised to 500–1,000 mg./ 100 ml.
The transition from prediabetes to diabetes may be induced by several factors such as progressive deterioration of insulin output or addition of diabetogenic factors like obesity and overproduction of human growth hormone. Hepatic glucose output in the prediabetic is regulated with a higher than normal efficiency, thus compensating for the deficient insulin secretion. The failure of this important mechanism may be a major precipitating factor for diabetes.
The future prevention and treatment of diabetes mellitus will depend on the development of agents that (a) correct the sensitivity of the glucose receptor of the beta cells and (b) stimulate the ability of the liver to suppress its glucose output.
Effect of Submaxillary Gland Extirpation on Glucose and Insulin Tolerance in Dogs
Authors: Steinberg Terry , Passy Victor , Gwinup Grant 
Published: December 2014

Serum glucose and immunoreactive insulin (IRI) responses to oral glucose and intravenous insulin tolerance tests were determined in dogs before and after total bilateral extirpation of their submaxillary glands. A comparison was made with a control group of dogs before and after sham operations. Postoperative studies were performed at one, three and six months after surgery. No significant differences in glucose and IRI responses were observed between the two groups of dogs, nor upon comparison of the responses within each group at the various periods studied.
A review of the literature which relates the salivary glands to diabetes mellitus in both experimental and clinical studies is presented. Our own experience of diabetes mellitus with apparent salivary gland involvement is briefly discussed.
It is concluded that despite the relatively frequent association of salivary gland involvement and diabetes mellitus, the role of these glands in the pathogenesis and management of diabetes mellitus is obscure. At this time there is no apparent rationale to the performance of total submaxillary gland extirpation for the treatment of diabetes mellitus.
Characterization of Glucose Metabolism in the Isolated Rat Heart During Fetal and Early Neonatal Development
Authors: Clark Charles M 
Published: December 2014

Uptake of 1-14-C glucose, lactate production, 14-C-CO2 production, glycogen content, and the incorporation of 1-14-C glucose into glycogen, protein, and lipid have been studied in isolated fetal and neonatal rat hearts from the sixteenth day of gestation to the fifth neonatal day. The effects of insulin (5,000 μU./ml.) on these processes was also studied.
Glucose uptake fell during gestation from 28.4 ± 2.2 to 10.0 ± 1.1 μmoles per gram wet weight tissue per two hours and remained constant after birth. At all ages insulin significantly increased glucose uptake. Lactate production Fell from 77.6 ± 11.5 to 51.5 ± 2.3 μmoles per gram wet weight per two hours between the sixteenth day of gestation and the first day after birth and was not influenced by insulin. Production of 14-C-CO2 from glucose was small (range: 2 to 7 per cent of glucose uptake) and was also unaffected by insulin. Hot KOH extractable cardiac glycogen content rose between the sixteenth and twenty-first day and then fell. The change in hot KOH extractable cardiac glycop; en followed similar changes in 1-14-C glucose incorporation into glycogen. Whereas 1-14-C glucose incorporation into tiot KOH extractable glycogen was unaltered by insulin until after birth, insulin did significantly augment the incorporation of 1-14-C glucose into the cold TCA extractable fraction. This fraction, which includes oligosaccharides destroyed by the hot KOH, also had a higher specific activity than the hot KOH extractable glycogen. The majority of the intracellular counts were in this fraction; the remainder of the counts were in the lactate and acetate or acetoacetate fraction. Insulin did not augment incorporation of 1-14-C glucose into these fractions. Incorporation of 1-14-C glucose into both protein and lipid was less than 2 per cent of glucose uptake and was not influenced by insulin.
The data suggest that fetal myocardial development is characterized by a progressive decline in glucose uptake which can be stimulated by insulin from the sixteenth day onward. The conversion of 14-C glucose to 14-C-CO2, protein, and lipid was not influenced by insulin. Incorporation of 1-14-C glucose into hot KOH extractable glycogen was augmented by insulin only after birth under the experimental conditions described. The cold TCA extractable glycogen had a higher specific activity and insulin stimulated the incorporation of 1-14-C glucose into this fraction. It is concluded that insulin augments glucose uptake and incorporation into a glycogen fraction turning over rapidly in the fetal rat heart.
Insulin and Insulinlike Activity in Extracts of Tumors Associated with Hypoglycemia
Authors: Abbasi Ali , Power Lawrence 
Published: December 2014

Insulin assays were performed on tissue extracts from ten nonpancreatic tumors and five islet-cell adenomas, all of which were associated with hypoglycemia. Acid alcohol and normal saline extractions were made from tumor tissue as well as from normal tissue. The insulin content of extracts was determined both biologically and immunologically, utilizing the rat epididymal fat pad to measure insulinlike activity (ILA) and the double antibody radioimmunoassay to estimate insulin (IRI).
All five islet-cell adenomas were found to have significant concentrations of biologically and immunologically active insulin. The nonpancreatic tumors had no significant concentration of insulin or insulinlike activity, but results were equivocal in one hepatoma. The mechanism by which such tumors induce hypoglycemia remains unknown. It does not appear to result from the elaboration of insulin or of products with insulinlike activity.
Regulation of Rat Hexokinase Isoenzymes: I. Assay and Effect of Age, Fasting and Refeeding
Authors: Bernstein Robert S , Kipnis David M 
Published: December 2014

A new and highly sensitive fluorimetric assay for hexokinase (HK) isoenzymes which requires only 5 μg. of tissue protein is described. This assay has been used to examine the alterations in the HK isoenzymes of rat skeletal muscle and adipose tissue under a variety of physiologic conditions. In both tissues, HK-II declined progressively with increasing age, reaching plateau levels in animals larger than 300 gm., whereas HK-I remained constant. HK-II activity decreased markedly in both tissues of young rats after a twenty-four to forty-eight hour fast and was restored after two days of refeeding. HK-I was not affected by the fasting-refeeding regimen. In older rats (300 gm.), adipose tissue HK-II did not fall during fasting but exhibited a significant rise when refeeding was instituted. “Pulsing” the fasted rat with periodic episodes of hyperglycemia (0.5 gm. glucose intraperitoneally every eight hours) did not prevent the fall in HK-II during fasting or restore HK-II activity in the two day fasted animal.
Approximately 50 per cent of HK-I, but little or none of HK-II, is bound to subcellular organelles in skeletal muscle. In adipose tissue, however, about one-third of the HK-II and insignificant amounts of HK-I are in the bound form. Ratios of bound to free HK are not altered during aging, but HK-II binding in adipose tissue is decreased during refeeding.
Normal mice exhibited a decrease in both adipose tissue HK isoenzymes with aging. Adipose tissue of sixteen week old obese hyperglycemic mice (obob) has lower HK-II and higher HK-I activity than that of normal litter mates, but no differences were detected in obob and normal mice at five weeks of age.
The changes in muscle and adipose tissue HK-II activity associated with aging and fasting-refeeding parallel the known changes in insulin sensitivity of these tissues under comparable conditions.
Diphenylhydantoin: Its Use in Detecting Early Insulin Secretory Defects in Patients with Mild Glucose Intolerance
Authors: Levin Seymour R , Reed James W , Ching King-Nien , Davis John W , Blum M Robert , Forsham Peter H 
Published: December 2014

Diphenylhydantoin (DPH) is known to inhibit insulin secretion in vitro and can cause hyperglycemia in man. To determine if there were selective effects of this drug in diabetes, insulin responses to intravenous stimuli were measured before and after ingesting the drug for several days in seven nonobese subjects with mild oral glucose intolerance. These were compared with responses of eight nonobese control subjects with normal oral glucose tolerance.
Before DPH, early insulin release after intravenous glucose was similar in both groups, though glucose clearance was subnormal in the glucose-intolerant group. Arginine, given thirty minutes after glucose (postglucose arginine) was followed by prominent insulin release in both groups. After DPH, there was no significant alteration in glucoseinduced earlyinsulin release or clearance of glucose, though downward trends were noted in both groups. However, after DPH, the glucose-intolerant group showed significant reduction of insulin responses to postglucose arginine.
These differences in drug effect occurred despite similar serum drug levels and per cent binding of DPH in the normal and in the glucose-intolerant group. Drug levels attained were in the effective range seen in patients taking DPH for epilepsy.
In the isolated, perfused rat pancreas, effects of DPH in the presence of a high arginine stimulus were differentiated from those of a glucose stimulus. Whereas DPH eliminated both early and late arginine-induced insulin secretion, only late glucose-induced secretion was abolished by the drug.
These data suggest that DPH will unmask early defects of insulin secretion in patients with mild oral glucose intolerance. The major early effect of the drug on insulin secretion in these patients is thus seen after a nonglycemic stimulus, postglucose arginine, which may have an insulinotropic mechanism distinctive from that of glucose.
Fetal Rat Pancreas: Differentiation of the Islet Cell Component in Vivo and in Vitro
Authors: Hegre Orion D , McEvoy Robert C , Bachelder Vesta , Lazarow Arnold 
Published: December 2014

Fetal rat pancreases, Day 16 through Day 22 postcoitum, were analyzed by immunoassay for insulin to assess islet cell development in vivo. The rise in pancreatic insulin concentration observed during gestation was relatively constant, amounting to 50 to 100 per cent per day, and was accompanied by increases in the total islet mass of the pancreas.
A difference was found in the potential of the pancreas for islet differentiation in organ culture which was related to the developmental state of the pancreas at the time of explantation. Highly differentiated islets of twenty-two day fetal pancreas were maintained in organ culture, while large increases in the islet mass occurred following organ culture of relatively undifferentiated eighteen day fetal pancreas.
Using the present organ culture system, explants can be produced which are composed of 25 per cent islet cells and contain 17 mU. of insulin activity per milligram.
Abnormal Serum Growth Hormone Response to Exercise in Maturity-onset Diabetics
Authors: Hansen Aage Prange 
Published: December 2014

Serum growth hormone was studied during a mild exercise load of 350 kgm. per minute for twenty minutes in four groups of subjects: nonobese normal subjects, obese normal subjects, nonobese maturity-onset diabetics and obese maturity-onset diabetics.
It was found that (1) the fasting pre-exercise serum growth hormone level was higher and the exercise response occurred earlier and was greater in diabetics than in normal subjects; (2) in the nonobese groups, the basal values and exercise responses in diabetics were significantly different from those of normal individuals. In the obese groups, the mean exercise response was higher in diabetics than in normals, but this difference was not significant; the basal values were identical in the two groups; and (3) the basal values and exercise responses were higher in nonobese diabetics than in obese diabetics. In normal subjects, the exercise responses were higher in the nonobese group than in the obese group.
Neuromuscular Junction Defect in Diabetes
Authors: Miglietta Osvaldo 
Published: December 2014

Neuromuscular transmission has been studied electromyographically in thirty diabeticpatients. The median nerve was stimulated rapramaximally at the wrist, and the evoked electrical response of the abductor pollicis brevis was recorded on a cathode ray oscilloscope. Pulse trainsof twenty to twenty-four stimuli were used in frequency varying from 2 to 500 per second.
In all patients the twitch rate of nerve stimulation was well maintained. Tetanic stimulation, however, was poorly sustained. A progressive decrement of the action potential amplitude occurred rapidly and earlier in many patients at frequencies that facilitated or left unchanged the amplitude in normal subjects. The drop in amplitude was particularly evident with trains of 50 and 100 per second.
He easy fatigability of neuromuscular transmission was present in clinically not involved nerve and muscle and could represent an early and only evidence of neuronal failure in diabetic patients.