bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Hyperglycemic Response to Intravenous Arginine in Prematurity-onset Diabetes
Authors: Sparks Lowell L , Copinschi Georges , Donaldson Charles L , Blum Andrea S , Forsham Peter H
Published: December 2014

L-arginine was infused (30 gm. per 30 min.) in normal subjects, mild maturity-onset and prematurity-onset diabetic subjects, all of whom were nonobese. Increases in blood glucose were slight in the normal subjects, moderate in the maturity-onset diabetics and marked in the prematurityonset diabetics. The maturity-onset diabetics had a poor immunoreactive serum insulin (IRI) response to arginine compared with the normal subjects. In the first two groups, there was a highly significant correlation between the IRI response to arginine and the subsequent fall in the blood glucose level at 60 min. The IRI response could not be evaluated in the third group because of antibodies induced by chronic insulin therapy. Arginine appears to be a useful tool in the study of the diabetic state. Abnormal glucose and insulin responses can be detected even in mild forms of the disease.
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.
Evaluation of an Eight-hour Therapeutic Regimen in Uncontrolled Diabetes
Authors: Metz Robert , Nice Marvin , LaPlaca Gerald
Published: December 2014

A treatment regimen based on the emergency program of Woodyatt has proved very satisfactory as a guide for house officers to the management of diabetes during acute complications. This report of the detailed results of treatment with the eight-hour regimen has been prompted by the absence of previous documentation of the efficacy of any of the similar methods in common use. In eighteen of twenty episodes in nineteen cases of uncontrolled diabetes, good control (by specified criteria) was established within an average time of two days. Hypoglycemic episodes were identified during eleven of the 530 treatment cycles.
Genetics of Diabetes Mellitus
Authors: Rimoin David L
Published: December 2014

The genetics of diabetes mellitus is a confused subject. There is good evidence that genetic factors are important in the etiology of diabetes, but little is known about the mode of genetic transmission. Conclusive studies will not be possible until the basic defect in diabetes is elucidated and a reliable marker for prediabetes obtained. The hypothesis that diabetes mellitus represents a genetically heterogeneous group of disorders is discussed.
Prolonged and Recurrent Tolazamide-induced Hypoglycemia: Report of a Case
Authors: Rull Juan A , Lennhoff Miguel
Published: December 2014

A case of recurrent hypoglycemic coma precipitated by tolazamide (Tolinase) at therapeutic dosage is here reported. The patient, an elderly woman with diabetes and renal failure, experienced several episodes of profound hypoglycemic coma, the last one forty-eight hours after withdrawal of the sulfonylurea. With this report, cases of prolonged hypoglycemia have been described with all currently available hypoglycemic sulfonylureas.
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 < 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.
Biological Properties of a Transplantable Islet-cell Tumor of the Golden Hamster: II. Insulin Content of the Tumor and Some Metabolic Characteristics of the Tumor-bearing Animals
Authors: Sodoyez Jean C , Luyckx Alfred S , Lefebvre Pierre J
Published: December 2014

Hamsters bearing a transplantable pancreatic tumor developed marked hypoglycemia upon fasting. Glucose assimilation constant and fasting plasma insulin levels were statistically higher in these animals than in the controls. The insulin content of the tumor (expressed in “humaninsulin equivalent” was 0.072 ± 0.014 U./gm. wet weight. Insulin could be extracted with acid-alcohol and inactivated with anti-insulin serum or cysteine. The possible significance of these findings is discussed.
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.
Estimation of the Long-term Control of Diabetes: The Relation of Blood Sugar Levels to Glycosuria
Authors: Caird F I
Published: December 2014

A simple and objective method of estimating the longterm control of diabetes and derived from urine terms tests at routine clinic attendances has been investigated. The per cent of such urine tests showing 2 per cent glycosuria (glycosuria percentage) is shown to be significantly related to the mean of blood sugars determined at the same attendances. This relationship is unaffected by the number of clinic attendances, if these number five or more.
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.
Carbohydrate Metabolic Studies After Six Cycles of Combined Type Oral Contraceptive Tablets: Measurement of Plasma Insulin and Blood Glucose Levels
Authors: Spellacy W N , Carlson K L , Birk S A
Published: December 2014

Thirty-two normal subjects were studied before and at the end of six cycles of treatment with a combined type of oral contraceptive. The tests involved measurement of blood glucose and plasma insulin levels during an intravenous glucose tolerance test. It was found that the mean blood glucose values were not different in the two groups. There was elevation in the plasma insulin levels in the drug treated group, but the degree of elevation could not be correlated with either familial history of diabetes mellitus or subject's weight change while taking the drug.
Arteriographic Demonstration and Successful Removal of Metastatic Islet Cell Tumors in Liver: A Case Report
Authors: Smrcka J , Bret J , Hauer J , Polomis V
Published: December 2014

A patient with organic hyperinsulinism is described. A malignant islet cell tumor in the head of the pancreas was found and removed. Because of persistent hypoglycemia, subtotal pancreatectomy was performed, but no additional tumor was found. A year later, total pancreatectomy, duodenectomy and resection of part of the stomach and jejunum were performed with failure again to find a tumor. Only by means of selective arteriography of the celiac artery were two tumors discovered in the right lobe of the liver. These were removed by resection of the lobe of the liver and histologically confirmed as metastatic islet cell tumor. After this operation there were no further hypoglycemic attacks but persistent diabetes ensued. The resection of the metastatic islet cell tumor took place three and one-half years after the initial hypoglycemic attacks. The patient is symptom-free four years after removal of the metastases.
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.
Biosynthesis of Insulin by the Isolated Perfused Dog Pancreas
Authors: Sevier B R , Whitney J E
Published: December 2014

Evidence is presented to show that the isolated, perfused dog pancreas is capable of incorporating C-14 labeled amino acids into fractions that have immunologically reactive and biologically effective insulin activity. The perfusion medium was recirculated through the pancreas from a reservoir for four hours. At the end of the perfusion, the pancreas, gut segment and medium were individually extracted and the active fractions separated on a Sephadex column. Each fraction was tested using the two antibody assay of Hales and Handle and the hemidiaphragm and fat pad assays. Peak 2 of the pancreas consistently had the greatest amount of IRI, ILA, and C-14 radioactivity. The in-corporation of C-14 amino acids into the fraction with ILA and IRI appeared to be an energy requiring process since 2,4-dinitrophenol completely blocked the appearance of C- 14 into the active fractions. It is concluded that the feasibility of the use of this preparation for studying of pancreatic hormones is demonstrated.
Disappearance of Immunoreactive Insulin in Normal and Adult-onset Diabetic Subjects
Authors: Stimmler L
Published: December 2014

Three units of porcine insulin were injected into a group of normal subjects and a group of adult onset diabetic patients who had never been treated with insulin. It was shown that the disappearance of immunoreactive insulin from plasma occurred at slower rates in the diabetic than in the normal group.
Renal Papillary Necrosis: Eight-year Survival of a Diabetic
Authors: Wright Jackson , Morin Lawrence J , Dunn John L
Published: December 2014

A case of eight years' survival of a diabetic patient after a well-documented episode of renal papillary necrosis has been presented. While several cases of long survival after papillary necrosis in nondiabetics who overuse analgesics have been reported, prolonged survival of a diabetic is apparently quite rare.
George Martin Guest, M.D. 1898-1966
Authors: Knowles Harvey C
Published: December 2014

The name of George Martin Guest is familiar to all investigators in the field of diabetes. His death on November 25, 1966, brought an end to a career unusually productive in the area of metabolic disorders. He had recently retired from his position as Fellow of the Children's Hospital Research Foundation and Professor of Research Pediatrics in the Children's Hospital Research Foundation and the University of Cincinnati College of Medicine.
Liver Glycogen Accumulation in Unstable Diabetes
Authors: Manderson W G , McKiddie M T , Glasgow  , Manners D J , Stark J R
Published: December 2014

Two patients who had severe unstable diabetes mellitus with frequent hypoglycemic episodes and who required soluble insulin for control are described. Both developed hepatomegaly. Quantitative and qualitative studies of liver glycogen and its related enzymes were performed. The liver glycogen content was high (8 per cent) but its molecular structure was virtually normal. Both the β-amylolysis limit and the phosphorylase activity appeared to be lower than normal but did not approach the levels associated with glycogen storage disorders. The values of the other enzymes tested were normal. Therefore it appears that the elevated liver glycogen levels seen in some patients with brittle diabetes mellitus are not the result of enzyme deficiency but are secondary to wide fluctuations in blood sugar and frequent doses of soluble insulin.
Diminished Serum Insulin Response to Glucose in Genetic Prediabetic Males with Normal Glucose Tolerance
Authors: Soeldner J S , Gleason R E , Williams R F , Garcia M J , Beardwood D M , Marble A
Published: December 2014

Serum immunoreactive insulin (IRI), plasma free fatty acids, and blood glucose were measured during an intravenous, an oral, and a cortisone-primed oral glucose tolerance test in each of eleven normal and five prediabetic (offspring of two diabetic parents) nonobese males, age twentyfive to thirty-four years. All normals and prediabetics had entirely normal blood glucose levels during each of the three tests. There were no significant differences between mean levels of serum insulin at any time period in any of the three types of tests. Serum IRI and blood glucose were significantly correlated in both normal and prediabetic groups during each of the three types of glucose tolerance tests. A linear regression equation of serum IRI (y) on blood glucose (x) was computed as an index for each type of test for each group and the regression coefficients (IRI in µU./ml per mg. per cent blood glucose) compared. A significantly lower slope was found for the oral and the cortisoneprimed oral glucose tolerance test in the prediabetic group. This suggests a diminished insulin secretory response to glucose in prediabetics who still maintained normal glucose tolerance. There was no evidence of a delay in the rise of serum insulin following a glucose load. There were no significant differences in mean plasma free fatty acids during each glucose tolerance test comparing prediabetics to normals. DIABETES 17:17-26, January, 1968.
Cryoablation of the Pituitary in the Treatment of Progressive Diabetic Retinopathy
Authors: Adams Donald A , Rand Robert W , Roth Nathan H , Dashe Alfred M , Heuser Gunnar , Hanley John , Parker Mary
Published: December 2014

Sixteen diabetic patients with sight-threatening progressive diabetic retinopathy who were carefully screened ophthalmologically, endocrinologically and medically, underwent stereotaxic transphenoidal pituitary cryoablation and were followed for an average of 26.2 months postoperatively. Hypophysectomy was complete or borderline in fifteen of the sixteen patients with no serious complications except chronic diabetes insipidus in one patient. Two patients died of nonsurgically-related conditions four and one-half and twentyfive months respectively after operation. Endocrine management was uncomplicated except for reversible cholestatic jaundice due to oral methyltestosterone in one patient. Insulin requirements were reduced in most instances following pituitary cryoablation. Ocular improvement occurred in ten of the sixteen patients with two patients stable, indicating a 75 per cent success rate. It is concluded that cryoablation offers a safe, reproducible, simple and effective method of pituitary ablation in well-selected patients with progressive diabetic retinopathy and threatening blindness.
Insulin Secretion in Rats with Elevated Levels of Circulating Growth Hormone Due to MtT-W15 Tumor
Authors: Martin Julio M , Akerblom Hans K , Garay Gabriel
Published: December 2014

Circulating levels of growth hormone (GH) in Wistar-Furth rats bearing the MtT-W15 tumor are twenty to thirty times higher than normal. The effect of constantly elevated levels of GH on the pancreatic islets was studied. Tumor-bearing rats (TR) and normal controls (C) were pair-fed for seven weeks. In TR, fasting serum levels of GH and insulin were 599 ± 157 ng./ml. and.142 ± 43 μU./ml., respectively, and only 18.2 ± 1.9 ng./ml. and 26.9 ± 7.9 μU./ml., respectively, in the controls. The islets of TR were enlarged with an islet/acinar ratio of 3.38 per cent (C: 0.82 per cent). The extracted pancreatic insulin was 9.84 ± 0.9 mU./mg. (C: 5.36 ± 0.4 mU./mg.). Incubated slices or isolated islets of TR pancreas released greater amounts of insulin when submitted to glucose stimulation. Incorporation of labeled leucine into insulin was increased also in TR. An exaggerated insulin response to a glucose load was found in vivo (peak value at 30 min., TR: 183 dt 42.5 μU./ml; C: 71 ± 17.9 μU/ml.). None of the TR became diabetic, however, and two to six weeks after removal of the tumors serum GH levels had returned to normal (17.2 μg./ml.) as had insulin levels both fasting (19.0 μU/ml.) and following a glucose load (56.4 μU./mg.). Insulin output by incubated pancreas decreased 50 per cent (26 μU./mg.). The islet/acinar ratio returned to normal but the insulin content remained high. These results indicate that in animals exposed to hjgh levels of endogenous GH there is an increased responsiveness of the islets to glueose stimulation.
Insulin Secretion in Vitro by the Pancreas of the Sand Rat (Psammomys Obesus)
Authors: Malaisse Willy J , Like Arthur A , Malaisse-Lagae Francine , Gleason Ray E , Soeldner J Stuart
Published: December 2014

The sand rat, when its diet is changed from pure vegetable to a mixed diet of vegetables and laboratory chow, often develops a diabetic syndrome, but may remain euglycemic or intermittently hyperglycemic. In the present study, insulin secretion by incubated pieces of pancreatic tissue from euglycemic and intermittently hyperglycemic animals fed a mixed diet was higher than that of control animals fed a pure vegetable diet. In the euglycemic and intermittently hyperglycemic rats, increased responsiveness of the pancreatic tissue to glucose, both in vitro and in vivo, was accompanied by morphologic signs of increased protein synthetic activity of the beta cells. Evidence of enlarged islets was often striking and beta cell degranulation was variable, so that the total insulin content of the pancreas remains generally normal or may be increased. In severely diabetic rats, the rate of insulin secretion induced by glucose in vitro was reduced; however, relative to the markedly reduced insulin content of the pancreas, a greater mobilization of the stored hormone is observed. The beta cells of these animals were filled with glycogen, and a reduction of the granular endoplasmic reticulum and other cell organelles was seen. It is suggested that the insufficient insulin supply and severe hyperglycemia at this stage of frank diabetes could be chiefly due to impaired insulin synthesis.
Effect of Insulin on the Hexosamine Content of Alloxan Diabetic Rabbit Vitreous Humor
Authors: Walker F , Path M C , Patrick R S , Path M C
Published: December 2014

The glucosamine concentration of rabbit vitreous humor is significantly elevated in the alloxan diabetic state. The glucosamine concentration is significantly lowered, towards normal values, when exogenous insulin is administered to such animals. These findings are most readily explained on the basis that in insulin deficient states glucose is preferentially utilized in the synthesis of glucosamine.
Pituitary and Adrenal Influence on Reduced Insulin B-Chain Induced Hyperglycemia
Authors: Fenichel Richard L , Bechmann William H , Alburn Harvey E
Published: December 2014

Hypophysectomized, adrenalectomized, and adrenal enucleated rats, maintained on a normal or a diabetogenic high-fat, high-protein diet, were used to investigate the role of the pituitary-adrenal axis on reduced B-chain-albumin induced hyperglycemia. Hypophysectomized and adrenal enucleated rats maintained on a normal diet did not show a reduced B-chain induced hyperglycemia, while adrenalectomized rats showed a significant hypoglycemia. Hypophysectomized, and adrenalectomized rats kept on a diabetogenic diet were insensitive to reduced B-chain hyperglycemia, but adrenal enucleated rats showed a significant hyperglycemia. These results indicate that the secretions of the adrenal cortex but not the adrenal medulla are involved in reduced B-chain-albumin induced hyperglycemia. Growth hormone and adrenocorticotrophic hormone replacement experiments with hypophysectomized rats kept on the diabetogenic diet indicated that while ACTH plays the more important role, the functioning of both of these hormones is necessary for reduced B-chain elicited hyperglycemia. Adrenalectomized rats on the diabetogenic diet and treated with corticosterone showed a significant and persistent B-chain induced hyperglycemia, demonstrating further that adrenocortical glucocorticoids are involved in this mechanism. The specificity of reduced B-chain induced hyperglycemia is demonstrated by the observation that the reduced A chain of insulin does not elicit this effect but instead induces a moderate but significant hypoglycemia.
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.
Plasma Cortisol Response to Insulin and Circadian Rhythm in Diabetic Subjects
Authors: Serio M , Tarquini B , Contini P , Bucalossi A , Toccafondi R
Published: December 2014

The behavior of blood glucose, plasma free fatty acids and cortisol has been studied after insulin administration in subjects with diabetes mellitus without known complications and with normal plasma cortisol circadian rhythm. The mean plasma cortisol response to hypoglycemia in the diabetic subjects was below that of the normal controls, but not statistically significant. The slower rise to normal in the diabetic group was probably due to the lesser degree of hypoglycemia.
Acute Insulin Withdrawal and the Regulation of Plasma Triglyceride Removal in Diabetic Subjects
Authors: Bagdade John D , Porte Daniel , Bierman Edwin L
Published: December 2014

The effects of acute insulin deprivation on the enzyme lipoprotein lipase (LPL) and on triglyceride (TG) removal from plasma in man are unknown. To assess the role of insulin availability on TG removal, plasma TG concentration and postheparin lipolytic activity (PHLA)—an indirect means of quantitating LPL—were measured in seven insulin-dependent diabetics before and forty-eight hours after insulin withdrawal. The TG elevation (p < .01) and diminished PHLA levels (p < .01) observed in all subjects were consistent with impaired TG removal. The delayed disappearance of C-14-labeled TG after insulin deprivation (p < .01) demonstrated in two subjects further suggests that insulin is required for maintaining normal LPL and TG removal.
Antithyroglobulin Antibodies in Diabetes Mellitus
Authors: Simkins Samuel
Published: December 2014

Tanned red-cell hemagglutination studies for antithyroglobulin antibodies revealed prevalences of 10.1 per cent clinically significant positive tests (titers 1/25 or greater) in a group of 317 euthyroid diabetic patients free of thyroid dysfunction and of 4.0 per cent positives in a control group of 424 nondiabetic, similarly euthyroid individuals. In both groups the positive tests were more common in the females than in the males and were almost all in those of forty years of age and over. Below age forty the prevalences of tests in the diabetic and nondiabetic subjects were almost equal and of low titer. The positive tests occurred most often in the fifty- and sixty-year age group in the diabetic patients and were less frequent in the aged (seventy and over), approaching the levels observed in the corresponding age bracket in the control group. The bulk of the increase in positive tests in the diabetic group was borne by the white female (23.9 per cent) and, to a lesser degree, by the negro female (12.3 per cent) in the fifty to sixty-nine age bracket. The findings do not permit any conclusion that the thyroid gland in diabetics is involved in autoimmune disease.
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.
Effects of Insulin on Metabolism of Perfused Livers of Rats Made Acutely Diabetic by Anti-insulin Serum Injection
Authors: Haft David E
Published: December 2014

Livers were taken from fed rats injected ninety to 120 minutes earlier with guinea pig anti-insulin serum and were perfused for four hours with and without addition of insulin to the medium. Glucose-l-C-14, glucose-6-C-14, and acetate-H-3 were added as tracers. The major changes from normal were (1) decreased initial glycogen content, (2) decreased fatty acid synthesis, and (3) decreases in oxidation to CO2 of both glucose-l-C-14 and glucose-6-C-14. Fatty acid synthesis was correlated with initial glycogen content, which varied widely even though the degree of hyperglycemia of the donor animal was quite consistent. Insulin added to the perfusate restored normal rates of glucose oxidation and stimulated fatty acid synthesis, although normal lipogenesis was not achieved. The data are consistent with mediation of the antiserum effects on the liver by plasma elevation of either unesterified fatty acid or glucagon.
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.
An Evaluation of Ketostix Strips
Authors: Watkins P J , FitzGerald M G
Published: December 2014

The usefulness of Ketostix as a semiquantitative screening procedure for the estimation of acetoacetate concentration in both plasma and urine has been established. Because of the reasonably constant relationship of β-hydroxybutyrate to acetoacetate, Ketostix also gives a good indication of the (β-hydroxybutyrate concentration. By reading the Ketostix after thirty seconds instead of the recommended fifteen seconds, the sensitivity of the reaction is increased. The use of Ketostix to examine the plasma from patients with diabetic acidosis will reliably distinguish ketotic from nonketotic cases and is strongly recommended for this purpose.
Pathological Findings after Long-term Sulfonylurea Therapy
Authors: Balodimos Marios C , Marble Alexander , Rippey John H , Legg Merle A , Kuwabara Toichiro , Gleason Ray E
Published: December 2014

An evaluation was made of postmortem findings in a group of fifty-five diabetic patients who were treated with sulfonylurea compounds, primarily tolbutamide, from twenty-four to 112 months, for a total of over 2,500 patientmonths and an average of 45.7 months per patient. The results were compared in “blind” fashion to the postmortem findings in two control groups: (a) fifty-five patients, closely matched to the former as to sex, age at death, and known duration of diabetes, who had been treated with insulin and had never received oral hypoglycemic agents; and (b) nineteen patients who had been treated exclusively by dietary restriction.

The frequencies of myocardial infarcts, cerebral vascular accidents, diabetic retinopathy and nephropathy, as well as neoplasms, thyroid disease, and ulcers of the stomach and duodenum were not statistically different in the three groups. Peripheral vascular disease (gangrene and/or amputations) occurred more frequently in the insulin-treatedgroup, probably because of the customary use of insulin in patients with these conditions. The findings do not provide evidence that the sulfonylureas influence the pattern ofdiseases or specific complications of diabetes when compared to suitable controls.

Islet cell tumors occurred more frequently in sulfonylurea treated patients when compared to the over-all experience of this hospital. The importance of such a finding has to be further substantiated.
Concentration of Chromium in the Hair of Normal Children and Children with Juvenile Diabetes Mellitus
Authors: Hambidge K Michael , Cantab B Chir , Rodgerson Denis O , O'Brien Donough
Published: December 2014

The concentration of chromium in the hair of thirty-three normal children and nineteen children with juvenileonset diabetes mellitus was measured by atomic absorption 8pectropholometry. The geometric mean for the group of normal children was 0.85 μg./gm.; range (mean ± 2 SD) 0.36 — 1.87 μg./gm., and for the diabetic children, 0.56 μg./gm. (range, 0.26 — 1.19 μg./gm.). Comparison of these results revealed a highly significant difference (p < 0.001) between the two groups.
Diabetes Mellitus in Athabaskan Indians in Alaska
Authors: Mouratoff George J , Carroll Nicholas V , Scott Edward M
Published: December 2014

Diabetes mellitus is infrequent in Athabaskan Indians in Alaska; this population has a high tolerance to a glucose load. In these respects, Athabaskans resemble Alaskan Eskimos. These two groups experience similar environmental stresses but are of quite different ethnic origin.
Effect of D-glucose or D-ribose on the Turnover of Glucose in Pancreatectomized Dogs Maintained on a Matched Intraportal Infusion of Insulin
Authors: Ishiwata K , Hetenyi G , Vranic M
Published: December 2014

It was found previously that in normal dogs D-glucose or D-(-)-ribose decrease the rate of endogenous (hepatic) glucose production. To investigate whether this effect is due to the release of extra insulin only, or to other factors as well, the following experiments were performed: Endogenousinsulin secretion was replaced by intraportal porcine or canine insulin infusion of 200 μU./kg./min. in conscious dogs. Such an insulin infusion commenced at time of removal of the remnant pancreatic autograft was able to maintain unchanged the plasma glucose level and the tracer determined glucose production and utilization. Three main conclusions emerged from this study: (1) Since an infusion of D-(-) -ribose did not affect concentration and turnover rates of glucose, it was concluded that ribose affects glucose metabolism only through an increase of the rate of insulin secretion. (2) The endogenous glucose production did not decrease in response to a glucose infusion at two thirds to twice the basal normal glucose production, even when the concentration of glucose in plasma exceeded 200 mg./100 ml. It is concluded that the release of extra insulin is indispensable for the regulation of glucose production in the normal dog. (3) The utilization of glucose rose in proportion to its concentration in the plasma in the absence of any change in the rate of insulin supply.
A Consideration of Methods of Insulin Assay
Authors: Ashford W R , Campbell J , Davidson J K , Fisher A M , Haist R E , Lacey A H , Lin B , Martin J M , Morley Nina H , Rastogi K Sudha , Storvick W O
Published: December 2014

The potency of “unknown” solutions of insulin has been determined by the U.S.P. rabbit method of assay. The same solutions have also been assayed by the mouse convulsion method, mouse hemidiaphragm method and by several immunoassay methods. The record shows reasonable agreement among the various methods which were used.
Mechanisms and Management of Hyperosmolar Coma Without Ketoacidosis in the Diabetic
Authors: Johnson Robert D , Conn Jerome W , Dykman Calvin J , Pek Sumer , Starr Jerome I
Published: December 2014

The mechanisms involved in the production, maintenance and progression of the state of nonketotic, hyperosmolar coma of mild diabetic patients are discussed; and a method is outlined for both initial therapy (before insulin activity is sufficiently increased) and subsequent therapy. Factors involved in the development of the syndrome include: (1) Persistence of enough insulin production to prevent ketoacidosis but very severe suppression of insulin release in relation to the level of blood glucose. (2) Insidious development of extreme hyperglycemia, increasingly great osmotic diuresis, severe depletion of body water and large volumes of urine. (3) Lack of appropriate response of the thirst center as the sensorium becomes inadequate.

Because the mortality of this condition now approaches 50 per cent, careful attention to details of therapy is imperative. Delay in recognition and, therefore, of therapy leads to fatalities.