bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organ Cultures of Pancreases of Fetuses from Diabetic Rats: Effects of High-glucose Media upon the Granulation of the Beta Cells and upon the Insulin Content of the Media
Authors: Wells Lemen J , Lazarow Arnold 
Published: December 2014

Forty pregnant rats were made diabetic by injecting alloxan intravenously on day 11.5 of pregnancy. On day 19.5 or day 21.5 the mothers were killed and their fetuses obtained for study. Pieces of fetal pancreases were grown in organ cultures on liquid media containing varying amounts of glucose for two to four days. At the time of the explantation, the beginning control pancreases contained virtually no granulated beta cells.
In cultures grown on the standard media (about 175 mg. of glucose per 100 ml.), the pancreatic islets had acquired many granulated beta cells. In those grown on the highglucose media (about 350, 500 and 1,000 mg. per 100 ml.) the islets had either few granulated beta cells or none. These observations complement our previous findings in pancreatic cultures from normal rat embryos.
The insulin content of the media after incubation was within the range of the insulin concentration in the blood of normal fed rats. The insulin content in the media after days 3-4 of culture was considerably greater than that after 1-2. The high-glucose levels in the media did not cause an increase in the insulin content of the media. Our studies suggest that the high-glucose levels in the media inhibited the synthesis (and/or storage) of insulin in the pancreatic culture.
The Natural History of Diabetes: I. Mortality
Authors: Hirohata Tomio , MacMahon Brian , Root Howard F 
Published: December 2014

Survival data are presented for five groups of diabetic patients seen at the Joslin Clinic, Boston, between 1939 and 1959. Patients were white, Massachusetts residents, and diagnosed diabetic within twelve months of first visit to the Clinic. The data are analyzed in terms of crude survival rates, relative survival ratios and mortality “attributable” to diabetes after the elimination of competing causes.
The excess mortality rate experienced by diabetic patients increases with duration of diabetes. While persons with juvenile onset experience virtually no excess mortality in the first fifteen years of the disease, between the fifteenth and the twenty-fourth year they have an excess death rate of 1 to 1.5 per cent per year. In the older age groups the excess is larger and appears earlier.
The mortality attributable to diabetes increases with increasing age of onset. Females have higher attributable mortality rates than males, particularly among cases with onset after forty years of age.
Patients first seen in 1944 had substantially better survival rates than those first seen in 1939. However, between 1944 and 1959 no further improvement has been evident. This leveling off in the former decline in diabetes mortality has occurred at a point when diabetic patients still experience an excess mortality of approximately 30 per cent within the first twenty-five years of their disease.
Fatty Metabolism and Ketogenesis after Liver Denervation or Bilateral Thoracolumbar Sympathectomy in Pancreatectomized Dogs
Authors: Houssay Bernardo A , Rietti Giro T , Ashkar Edmundo , Castillo Enrique J Del , Galli María Elisa , Roldán Alicia , Urgoiti Enrique J 
Published: December 2014

Bilateral extirpation of sympathetic chains from Tl to L6, including stellate ganglia and splanchnic nerves in totally pancreatectomized dogs, induces in blood: no changes in the diabetic hyperglycemia or cholesterolemia, but decrease of fatty acid mobilization from adipose tissue (lower values of FFA and lipemia), and a striking diminution of the diabetic ketonemia. In the liver, as in pancreatectomized dogs, there is less increase of total lipids (and triglycerides) but high values of cholesterol.
Acute hepatic denervation in pancreatectomized dogs does not change the mobilization of fatty acids from adipose tissue (the high levels of hyperlipemia and FFA are similar to those of pancreatectomized controls), but the increase of the ketonemic level is markedly depressed. Glycemia and cholesterolemia are increased as in the pancreatectomized dogs. In the denervated liver there is less increase of total lipids, triglycerides and cholesterol as compared with the pancreatectomized controls.
In the pancreatectomized dogs with chronic hepatic denervation the blood changes are similar to those of the pancreatectomized dogs. There is no attenuation of ketonemia. In the liver the cholesterol content is strikingly diminished as compared with the pancreatectomized controls. The diabetic hyperglycemia is high after pancreatectomy either after sympathectomy or hepatic denervation.
Abnormally Increased Glomerular Filtration Rate in Short-term Insulin-treated Diabetic Subjects
Authors: Ditzel Jørn , Schwartz Michael 
Published: December 2014

Functional changes in the microvascular system appear to precede the morphological changes in the conjunctiva and retina of young subjects with diabetes mellitus. Similar functional changes might occur in the renal microvascular system and hemodynamics and possibly lead to a disturbance in the glomerular filtration rate.
A preliminary study of the glomerular filtration rate (GFR) using the radioactive vitamin B12 method in young, insulin-treated patients with short duration of diabetes is reported.
The average GFR in eighteen diabetic subjects was 137.8 ml. per min. per 1.73m2 with a standard deviation of 24.3 ml. in contrast to the average GFR in twelve control subjects which was 102.9 ml. with a standard deviation of 15.1 ml. This difference in GFR is highly significant. The reasons for the increased GFR in diabetics with short duration of their disease are discussed.
Blood Sugar Response to Electric Shock Stress in Normal, Adrenalectomized and Hypophysectomized White Rats
Authors: Ehrentheil Otto F , Reyna Leo J , Adams Constance J , Giovanniello Thomas J , Chen Edith T 
Published: December 2014

Groups of normal (nonoperated), two-month-old and eight-month-old rats were subjected to a daily buzzer and electric shock stress program for five weeks. Blood sugardeterminations were made immediately before and after ninety-minute stress (experimental group) or rest periods (controls). There was a small but statistically highly significant increase in blood sugar after stress compared to the prestress values at both age periods. This increase was much bigger in the older than in the younger group of fasted normal rats.
Groups of adrenalectomized animals subjected to the same stress program never showed any significant blood sugar increase after stress. Indeed the nonfasted, recently operated, two-month-old rats displayed a highly significant drop in blood sugar after stress.
Recently hypophysectomized, two-month-old nonfasted rats showed a decrease in blood sugar after stress but their nonstressed controls showed a similar decrease. Fasting two-month-old, hypophysectomized rats were found to have an insignificant increase after stress which became significant only when compared to the drop in blood sugar of their nonstressed controls. In contrast eight- and ten-month-old hypophysectomized fasted rats showed a highly significant increase in blood sugar after stress. Moreover, the magnitude of this increase was much greater in those rats in which more than six months had elapsed sincethe operation compared to the recently hypophysectomized animals of approximately the same age. Thus the influence of both the time lapse since the operation and the age of the animals on the blood sugar response to stress is demonstrated in the hypophysectomized rats.
Studies in Vivo and in Vitro of Glucose-Stimulated Insulin Release: The Effects of Metabolizable Sugars, Tolbutamide, and 2-Deoxyglucose
Authors: Kilo Charles , Devrim Sevim , Bailey Rita , Recant Lillian 
Published: December 2014

The role of glucose as a stimulant to pancreatic insulin release was studied in the intact dog and in rat pancreas incubated in vitro. The infusion of the metabolizable sugars, glucose, fructose, and mannose, as well as tolbutamide into the pancreatico-duodenal and splenic arteries in the anesthetized dog resulted in increased portal vein insulin-like activity, using the epididymal fat pad assay. Normal saline and pyruvate infusions resulted in no significant increase in insulin-like activity. Infusion into the dog of the glucose analogue, 2-deoxyglucose, at high concentration resulted in no stimulation of insulin release, but in fact blocked the pancreaic response to simultaneous glucose infusion. It appeared that the ratio of glucose: 2-deoxyglucose was a determinant in the degree of inhibition. Plasma ratios of &lt; 1.5 resulted in inhibition.
Incubation of rat pancreas with 2-deoxyglucose in the presence of glucose showed that 2-deoxyglucose inhibited the release of immunoassayable insulin. The inhibition was dependent upon the concentration of 2-deoxyglucose and the ratio of glucose: 2-deoxyglucose.
In view of the metabolic blocking action of 2-deoxyglucose in the utilization of glucose-6-phosphate, it is suggested that the glucose stimulated insulin release occurs after the formation and further metabolism of glucoses-6-phosphate.
Influence of Anti-insulin Serum on Glucose Metabolism: I. In Isolated Adipose Tissue
Authors: Beloff-Chain Anne , Catanzaro R , Chain E B 
Published: December 2014

1. A consistent in vitro effect of anti-insulin serum on glucose metabolism in isolated rat adipose tissue has been demonstrated.
2. Anti-insulin serum added in vitro to epididymal fat pads caused an average decrease in the C-14-O2 formation from glucose-1-C-14 of over 50 per cent, whereas it reduced the incorporation of glucose-U-C-14 into lipids by about 20 per cent.
3. Epididymal fat pads pretreated in vitro with antiinsulin serum oxidized glucose-1-C-14 at a reduced rate compared to control fat pads preincubated in buffer; in the presence of added insulin, however, glucose oxidation was the same in the control and anti-insulin treated fat pads.
Diabetic Insulin Antagonism
Authors: Power Lawrence , Shuman John 
Published: December 2014

A capacity of freshly-drawn, normal serum to antagonize the action of insulin in the epididymal fat pad system has been found to be increased in the serum of untreated diabetic patients. A comparable increase has also been found in the serum of very obese subjects who are not apparently diabetic.
The current status of insulin antagonism in diabetes has been briefly reviewed. Although a search for the diabetogenic insulin antagonist has been under way for several decades now, failure thus far to convincingly demonstrate its presence appears to have carried little conviction of its absence. To the several candidates currently in nomination, another has been added.
Diminished Insulin Response to Hyperglycemia in Prediabetes and Diabetes
Authors: Colwell John A , Lein Allen 
Published: December 2014

Three principal findings have resulted from this study: (1.) The plasma insulin response to glucose loading is lower in prediabetics than in normal individuals. This phenomenon, while apparent when the glucose and insulin curves are expressed as a function of time, can be better demonstrated and quantitated by expressing plasma insulin concentration as a function of glucose concentration during the early portion of the glucose tolerance curve. The findings in this report suggest the sensitivity of the pancreatic β cells of prediabetics to glucose stimulation is lower than that of normal persons.
(2.) A low plasma insulin response to glucose loading is also seen in nonobese diabetic subjects. However, since these patients had elevated plasma glucose concentrations with insulin levels like those of the prediabetics, one must suspect that insulin in this group was less effective than in prediabetics in exerting its influence on blood glucose. Whether this is due to antagonists to insulin action or to physiologic defects in the immunoreactive insulin molecule has not been determined in this study.
(3.) The same method of relating plasma insulin to glucose concentration was used in assessing the insulin secretion in an obese diabetic population. Diabetics with fasting glucose values in excess of 150 mg. per 100 ml. reveal a decreased insulin response to glucose stimulation. These findings suggest a decreased sensitivity of the β cells to glucose stimulation in this group.
Further Studies on an Abnormal Insulin of Diabetes Mellitus
Authors: O'Brien Donough , Shapcott Dennis , Roy Claude C 
Published: December 2014

Insulin isolated from normal and diabetic pancreas was isolated and injected intraperitoneally into rats together with C-14 glucose. Measurement of C-14 incorporation into the diaphragm showed a significantly lesser biologic activity for diabetic insulin.
These results are in accord with earlier work on the resistance of diabetic insulin to insulinase and on the inheritance of diabetes in terms of the abnormal insulin. The possibilities for a mutation site in the insulin molecule are discussed in relation to known molecular variations.
Effect of Pituitary Ablation on the Renal Arteriolar and Glomerular Lesions in Diabetes
Authors: Ireland J T , Patnaik B K , Duncan L J P 
Published: December 2014

Renal tissue of six diabetics having proliferative retinopathy was obtained before and one to two years after pituitary surgery and examined by light and electron microscopy. Successful pituitary ablation was followed by significant reduction in the thickness of the glomerular capillary basement membrane, restoration of the atrophic endothelial and mesangial cells to their normal appearance, persistence of the morphological features suggesting overactivity of the epithelial cells and no improvement in the arteriolar lesion.
These observations and changes suggest that diabetic nephropathy results from the development of several separate though inter-related lesions each of which may be variously influenced by the metabolic disturbance, the inherited diabetic diathesis or pituitary activity. Hypophysectomy will not alter the progressive clinical course of diabetic kidney disease if significant renal arteriosclerosis is present.
Insulin Secretion by Insuloma and Normal Pancreas Slices: Studies in a Patient with Multiple Endocrine Adenomata
Authors: Colwell John A , Furey Warren L 
Published: December 2014

A case of multiple endocrine adenomata and polycystic kidneys is reported. Functioning adenomata of the parathyroids and pancreas were removed surgically and a pituitary adenoma was associated with galactorrhea and amenorrhea.
Serial plasma glucose and insulin determinations during sixteen months of observations confirmed the temporary efficacy of tumor resection and partial pancreatectomy for islet cell adenomata. The suspected presence of multiple pancreatic islet cell adenomata, not removed at surgery, was confirmed when hyperinsulinism and hypoglycemia returned several months postoperatively. With benzothiadiazine therapy, plasma glucose levels rose and insulin concentrations fell, suggesting that these drugs exert a diabetogenic effect primarily through inhibition of insulin secretion. This effect does not appear to be mediated through an adrenal mechanism since it was seen in spite of bilateral adrenalectomy in this patient.
Evidence is presented which conflicts with the usual explanation for diabetic glucose tolerance curve in patients with functioning islet cell adenomata. In vitro studies with apparently uninvolved pancreas slices revealed that insulin secretion was stimulated by increasing concentrations of glucose. Insulin release occurred in vivo following oral glucose. Portal venous plasma insulin levels fell markedly only after resection of the normal tail of the pancreas. These findings indicated that there was no suppression of insulin output from the apparently uninvolved pancreas by the hyperinsulinemia associated with the tumor. During glucose tolerance testing, hyperglycemia was associated with hyperinsulinemia, a finding which supports a peripheral insensitivity to insulin's hypoglycemic action as a probable mechanism for the diabetic glucose tolerance in this patient.
Finally, evidence is presented that apparently uninvolved pancreatic tissue responds in vitro to mannose, glucose, leucine and tolbutamide. The response to glucose can be blocked by 2-deoxyglucose, an agent which blocks the metabolism of glucose 6-phosphate.
These findings suggest that insulin release in man is related to glucose phosphorylation or some product of glucose 6-phosphate metabolism.
Role of the Kidney in Insulin Metabolism and Excretion
Authors: Rubenstein A H , Spitz I 
Published: December 2014

The role of the kidneys in insulin metabolism and excretion is reviewed. Removal of these organs from animals prolongs the half-life of injected labeled or unlabeled insulin. Similar findings, reversible by transplantation, are noted in patients with severe renal disease. After injection of insulin-I-131 into a peripheral vein, the concentration of radioactivity in the renal cortex of rats is nine times greater than any other tissue and 21 per cent of the administered dose is present in the kidneys at fifteen minutes. In contrast to other organs, an increase in the injected dose results in a greater proportion being localized to the kidneys.
The concentration of insulin in renal venous blood is 30 to 40 per cent lower than the arterial level, and the quantity of insulin removed by the kidneys over twentyfour hours is 6 to 8 U. The renal clearance of insulin in man is approximately 200 ml. per minute. There is both direct and indirect evidence that insulin is filtered at the glomerulus and almost completely reabsorbed and degraded by cells lining the proximal convoluted tubules. This mechanism accounts for 50 to 60 per cent of the renal uptake of insulin, the remaining 40 to 50 per cent being removed from the postglomerular peritubular capillaries. The amount of insulin excreted in the urine is less than 2 per cent of the filtered load and the urinary clearance is 0.1-0.5 ml. per minute. This clearance is constant over a wide range of serum levels and is thus a useful reflection of the mean serum level over a period of time.
These observations explain the fall in insulin requirements of diabetic patients who develop renal failure. Furthermore, the severe hypoglycemia which occasionally occurs in elderly subjects with uremia following the administration of oral sulfonylureas may be partly due to this mechanism.
Effect of Muscular Exercise on Insulin Secretion
Authors: Nikkilä Esko A , Taskinen Marja-Riita , Miettinen Tatu A , Pelkonen Risto , Poppius Hakan 
Published: December 2014

Studies were carried out to define the possible role of insulin in the increased assimilation of glucose caused by exercise. First, plasma immunoreactive insulin (IRI) response in conventional intravenous glucose tolerance tests was measured in normal subjects at rest and during or immediately after ergometer exercise. In all cases the glucose disappearance rate (K value) was increased by exercise but the plasma IRI level assayed at two minutes after glucose showed no constant change from corresponding values at rest. Secondly, the insulin secretion rate was assessed by giving I-131-labeled insulin as a constant-rate infusion and measuring the plasma IRI specific activity. In the fasting state the insulin secretion rate varied from 0.7 to 6.0 mU. per min., and was highest in obese subjects. Increase of blood glucose level to 130-150 mg. per 100 ml. with a constant-rate glucose infusion doubled the insulin secretion rate. In subjects with a normal working capacity moderate exercise of thirteen to twenty minutes' duration did not significantly change the secretion rate whether the muscular work occurred in the fasting state or with glucose infusion. On the contrary, in all subjects with a reduced performance due to coronary heart disease the insulin secretion rate was strikingly increased by exercise and the plasma IRI level rose.
It is concluded that immunoreactive insulin is not the mediator of accelerated glucose metabolism caused by muscular work but that hypoxia of islet tissue may be a stimulus to insulin release.
Diabetes Among the Chinese in Hong Kong
Authors: McFadzean A J S , Yeung Rose 
Published: December 2014

In 1955-66, 1,085 Chinese with diabetes came under the care of the University Department of Medicine. In 1966, the crude death rate from diabetes in Hong Kong was 3.2 per 100,000 and this is, for reasons advanced, thought to be lower than the actual death rate. It is concluded that diabetes is certainly not the rarity among the Chinese that it has been reported to be.
Diabetes among the Chinese was found to differ in a few particulars from diabetes in the West. Diagnosis before the age of forty was slightly less common: 20 as against 25 per cent. The majority of patients of both sexes were either of normal weight or were underweight and, in some, active pulmonary tuberculosis, which had a prevalence of twenty times that encountered in the general population, played a part. Both the number overweight and its degree were very much less than among diabetic patients in the West.
There were two striking additional differences in that there was a very low prevalence of myocardial ischemia, and of occlusive peripheral vascular disorder (4.7 and 1.4 per cent respectively). Nevertheless, the prevalence of each was much higher among diabetic than among nondiabetic admissions to hospital. It is concluded that the low rates of these two conditions reflect their low rates in the population as a whole and do not infer a fundamental difference in the diabetes per se.
Dupuytren's contracture was not encountered, but this is not surprising for the diathesis does not seem to occur among the Chinese. There was a higher prevalence of “frozen shoulder” and of tenosynovitis leading to “trigger finger” in diabetics than in nondiabetics and these complications, as far as we are aware, have not been reported previously.
In other ways the characteristics of the Chinese diabetic patient in Hong Kong resembled his counterpart in the West. The over-all sex incidence and the preponderance of women after the age of forty were as in the West. Severe diabetic ketosis was encountered in 6.0 per cent. Hypertension occurred equally commonly, and the eye, renal and neurological complications differed neither in prevalence nor severity from those seen in diabetic populations in the West. For the first time retinitis proliferans, which occurred in eleven of 156 patients with retinopathy, is reported in Chinese diabetics as is also the occurrence of painless parotid enlargement in six patients, a complication which would appear to be a rarity in the West.
It is concluded that diabetes mellitus, certainly among the Chinese in Hong Kong and, perhaps, elsewhere, is not the mild disease it has been claimed to be. The concept, that climate was responsible for the high prevalence and severity of diabetes in temperate regions and for a low frequency of a mild form of diabetes in tropical and subtropical regions is not borne out by the present study.
Control of Diabetic Diarrhea with Antibiotic Therapy
Authors: Green Paul A , Berge Kenneth G , Sprague Randall G 
Published: December 2014

The ability of oral antibiotic treatment to control diabetic diarrhea was documented by a double-blind study involving a patient with this condition. When the patient was given Mysteclin-F, the diarrhea subsided promptly, only to recur when a placebo was substituted,. The erratic behavior of diabetic diarrhea is indicated, however, by the fact that a remission eventually occurred, and no further treatment was required.
Although not all patients with diabetic diarrhea respond to antibiotic treatment, its trial merits consideration forthose patients who are refractory to the simpler forms of treatment.