bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperinsulinism-Hypoglycemia in the Postgastrectomy Patient
Authors: Roth Donald A , Meade Robert C
Published: December 2014

Patients who had undergone gastric resection were studied with blood glucose and serum insulin levels during oral glucose tolerance testing. The symptoms which appear two to three hours after a glucose load follow a marked rise in serum insulin and are accompanied by hypoglycemia. By appropriate elevation of the blood glucose, high seruminsulin levels and a similar secondary hypoglycemic syndrome can be produced in normal individuals.
The Extractable Insulin Content of Pancreas from Fetuses and Infants of Diabetic and Control Mothers
Authors: Steinke Jurgen , Driscoll Shirley G
Published: December 2014

The acid ethanol extractable insulin content of pancreases from thirty-seven infants and three early fetuses of diabetic and control mothers has been measured and their islet cell histology was studied. In general there was good agreement between these two parameters.

Pancreatic insulin could be detected in one of two twelve-week old fetuses examined and in the pancreas of a fourteen-week old fetus of a diabetic mother. The remaining thirty-seven pancreases were obtained from fetuses of gestational age twenty weeks to term, nine of whom were offspring of diabetic mothers. The latter contained more insulin than the corresponding control group. The possible mechanisms are discussed; the hyperglycemic hypothesis is favored.
Glucose Metabolism in Leucocytes from Patients with Diabetes Mellitus, with and without Hypercholesteremia
Authors: Munroe John F , Shipp Joseph C
Published: December 2014

The metabolism of glucose by the Embden-Meyerhof, pentose cycle and citric acid cycle pathways was determined in human polymorphonuclear leucocytes from control subjects and from patients with diabetes mellitus, with and without hypercholesteremia.

In controls over 85 per cent of glucose uptake was metabolized to lactic acid by the Embden-Meyerhof pathway; about 5 per cent of glucose uptake was recovered as Co2, mostly from oxidation in the pentose cycle. Minimal citric acid cycle activity, a finding which correlated well with the paucity of mitochondria in the leucocyte, was shown by the slight and similar degree of oxidation of pyruvate and acetate.

Glucose metabolism in leucocytes from diabetics differed in two respects. The per cent of glucose uptake oxidized in the pentose cycle was increased in leucocytes from all diabetics. In the insulin-treated diabetics glucose uptake and lactic acid formation were similar to controls. In contrast, glucose uptake and lactic acid formation were reduced in leucocytes from adult, latent, hypercholesteremic diabetics. Pyruvate and acetate oxidation was similar in diabetics and controls. Thus, in terms of leucocyte metabolism, hypercholesteremia in the human diabetic was correlated with reduced glycolysis and not with reduced pentose cycle activity.
Effect of Endogenous Insulin on Human Amino Acid Metabolism
Authors: Zinneman Horace H , Nuttall Frank Q , Goetz Fred C
Published: December 2014

This study describes the effect of endogenous insulin on free plasma amino acids. The secretion of insulin was provoked by means of a standard glucose tolerance test.

Four healthy males responded by a drop in the levels of all twenty-two plasma amino acids, which were measured. In four insulin-dependent diabetics the glucose tolerance experiment effected only slight decreases in nineteen of twenty-two amino acids. Ornithine and histidine decreased significantly, whereas phenylalanine increased.

The over-all result indicates that endogenous insulin reduces the levels of the majority, if not all, free plasma amino acids.
Structural and Functional Characteristics of Neonatal Pancreas Homografts in Alloxan Diabetic Golden Hamsters
Authors: Sak Matthew F , Macchi I A , Beaser Samuel B
Published: December 2014

The present study extends preliminary investigations on the release of insulin-like activity (ILA) by pancreatic homografts.

Neonatal pancreas was implanted into the cheek pouch of alloxan-diabetic golden hamsters maintained with insulin. Hosts were treated additionally with cortisone and tolbutamide either singly or in combination. Homografts were evaluated structurally (aldehyde fuchsin) and functionally (fat pad bioassay) at periodic intervals.

In hosts receiving insulin alone, revascularization of the homografts occurred generally by seven days and complete exocrine degeneration by thirty days. The former process was delayed by cortisone and the latter accelerated by tolbutamide but delayed by cortisone. Cortisone prevented lymphocytic infiltration while tolbutamide significantly increased the number of islets with mitotic figures.

The number of homografts with islets demonstrating ILA in vitro was increased when hosts were pretreated with cortisone and insulin one week before transplantation and tolbutamide and insulin after transplantation. Arbitrary scoring of the survival and functional capacity of the homografts indicated this treatment to be twenty-eight times more effective than treatment with insulin alone. The magnitude of ILA released per transplant was not significantly different as a result of different treatments. However, omission of tolbutamide for twelve days prior to bioassay significantly increased the number of homografts able to release ILA. This suggests that the functional deficiencies observed with uninterrupted tolbutamide treatment may have resulted from overstimulation above that occurring as a consequence of diabetic hyperglycemia.
Glucose Tolerance, Nutrition, and Diabetes in Uruguay, Venezuela, Malaya, and East Pakistan
Authors: West Kelly M , Kalbfleisch John M
Published: December 2014

In each of four countries (Uruguay, Venezuela, Malaya and East Pakistan) where diets and other environmental factors differ greatly, the prevalence of diabetes as determined by impaired glucose tolerance was crudely estimated.

Since all subjects received glucose loads, rates of prevalence are much higher than those obtainable by certain less sensitive standard methods. In the tested subjects over thirty years of age the prevalence of “diabetes” (two-hour venous blood glucose levels greater than 149 mg. per 100 ml.) was 6.9 per cent in Uruguay (6.8 per cent for males and 6.9 per cent for females). The prevalence of impaired tolerance in this age group in Venezuela was 7.3 per cent (4.5 per cent in males and 9.4 per cent in females), while in Malaya the rate was only 3.5 per cent (4.5 per cent in males and 2.1 per cent in females). In East Pakistan impaired tolerance was present in only 1.5 per cent of this age group (1.2 per cent of males and 2.8 per cent of females). Comparable data are not available in the United States but with use of the technics employed abroad it was found that 17.2 per cent of volunteers in this age group in a Pennsylvania community had impaired tolerance.

In East Pakistan, 83 per cent of calories were derived from carbohydrate. Comparable figures were 77 per cent for Malaya, 62 per cent for Venezuela and 53 per cent for Uruguay. In East Pakistan, only 7 per cent of the dietary calories were derived from fat; in Malaya, fat accounted for 21 per cent of dietary calories, in Venezuela, 24 per cent, and in Uruguay, 33 per cent. In East Pakistan only 29 per cent of dietary fat was animal fat. In Malaya, Venezuela, and Uruguay, comparable figures were 30, 35 and 62 per cent, respectively.

In Uruguay, 34.4 per cent of the subjects were “obese” (30 per cent or more over “standard” weight), and in Venezuela 14.8 per cent were obese. In contrast none of the subjects from Malaya (566 persons), or East Pakistan (519 persons), was obese by these criteria.

In Venezuela and Uruguay there was an association between the prevalence of diabetes and both parity and a history of large babies.
Hyperosmolar Nonketotic Diabetic Coma
Authors: Jackson W P U , Forman R
Published: December 2014

Twelve cases of diabetic hyperosmolar coma without ketosis are described in ten patients. Seven of these were complicated by other illnesses. Seven died, but in five death Was probably not due to the hyperosmolar state. One had a pancreatic carcinoma; others in the literature are reported to have had pancreatitis.

The hyperosmolarity in this syndrome is due to either gross hyperglycemia or hyperelectrolytemia or both. Focal or generalized seizures occur in some cases. Very hypotonic neutral fluid in Targe quantities appears to be essential in the treatment in addition to insulin.

No case has been reported in a young person and all patients have been either new diabetics or their diabetes has been previously mild, and remains mild in those who live.

The absence of ketosis is possibly due to a block in the metabolic pathway of fatty acid breakdown. Hyperosmolarity must also be considered as a factor in the coma associated with ordinary diabetic ketosis.
Augmented Insulin Secretion Due to Growth Hormone: Stimulating Effects of Glucose and Food in Dogs
Authors: Campbell James , Rastogi Krishna Sudha
Published: December 2014

In iinanesthetized dogs, portal vein (PV) blood was repeatedly sampled by means of an indwelling cannula, simultaneously with blood from a superficial vein (SV), for determination of insulin by two-antibody immunoassay. Under control conditions, and in the postabsorptive state, mean serum insulin in the SV was 31 μU. per milliliter, and the PV/SV ratio was about 2. Following intravenous injection of 1 gm. of glucose per kilogram of body, serum insulin rose in 15 to 30 min. to peak values that were higher in the PV, and regressed to normal in 60 to 120 min. Growth hormone, 2 mg. per kilogram of body, injected daily for six to thirteen days, (1) increased PV and SV “fasting” serum insulin to the maximum of tenfold; the effect was found after one day of injection, was maintained during injection, and returned to normal within four days of ceasing injection; (2) caused a further increase in serum insulin, in 100 min. following a meal, to a greater extent in the PV than in the SV; and (3) enhanced the rises in serum insulin in PV and SV following intravenous injection of glucose, to maxima of nine- and sixfold, respectively; these rises were prolonged and the rates of regression regression of serum insulin from the peak values were reduced. Similar effects of growth hormone treatment were found in dogs under anesthesia at the time of glucose infusion. It is concluded that, during the treatment of several days, growth hormone caused continuously maintained increase in insulin secretion with enhanced secretion in response to a meal, and to the injection of a standard load of glucose.

Further effects of growth hormone on serum were: (a) free fatty acid levels rose promptly, and remained above normal; (b) glucose tended to increase; (c) the insulin/glucose ratio increased—the values were consistently reater in the PV than in the SV; and (d) in response to the glucose load, the rate of regression of serum glucose was reduced. The insulin/glucose ratio tended to remain stable at the particular “fasting” value, following glucose injection, both under the control conditions and during growth hormone treatment. This evidence indicates that growth hormone caused readjustment of the homeostatic control of the pancreatic islets such that, at any particular level of glucose in the blood, insulin was secreted at a higher rate.
Effects of Prolonged Fasting on Insulin Secretion
Authors: Genuth Saul M
Published: December 2014

The effects of total starvation upon response to glucose and tolbutamide were studied in obese nondiabetic and in obese diabetic individuals. Response was determined by serial measurement of plasma insulin, glucose, NEFA, and beta-hydroxybutyrate levels. In confirmation of other reports, obese diabetics had significantly greater plasma insulin responses to glucose and tolbutamide prefasting. Following a prolonged fast, obese nondiabetics developed increased insulin resistance manifested by impaired glucose tolerance without significant change in plasma insulin response. In contrast, obese diabetics had little further deterioration in glucose tolerance or increase in insulin resistance. In both groups studied, the response of blood glucose and plasma insulin levels to tolbutamide was unaltered by caloric deprivation. Carbohydrate intolerance of fasting appeared best explained by increased contra-insulin factors and decreased islet cell responsiveness to glucose. Fasting, for at least seven days, failed to reproduce in the nondiabetic obese individuals the patterns of response to glucose and tolbutamide seen in obese diabetic subjects.
Studies on Experimental Insulin Immunity: I. Dynamics of Insulin Immunity in the Guinea Pig
Authors: Horino Masaharu , Yu Shiu Yeh , Blumenthal Herman T
Published: December 2014

Insulin half life and the formation and characterization of the insulin-binding antibodies have been studied in the guinea pig both in vivo and in vitro. The antigen-antibody complexes have also been studied utilizing cellulose column electrophoresis and Sephadex G-200 column filtration. In addition, a quantitative assay procedure for insulin-binding antibodies has been employed.

In normal guinea pigs the injected insulin-I-125 is carried by at least two serum proteins, presumably albumin and an α. globulin, or more specifically 4.5S and 19S proteins. In immune animals the insulin-antibody complexes are represented by a single peak in the (β-γ globulin region on column electrophoresis; they are distinguishable from the uncomplexed antibodies which are 7S γ1 and 7S γ1 globulins. The precipitating insulin antibody also appears to be a 7S globulin. Moreover, the insulin-antibody complexes occur as a single component in the 19S fraction on Sephadex G-200 filtration, and if the complex were a single molecule it would have a molecular weight equivalent of about 630,000.

During the immunization process the insulin binding antibody titer increases progressively in association with an elevation of 7S globulin. In most animals during the early stages of immunization the molecular weight of the antibodies appears to be exclusively of the 7S globulin type; however, in two of seven animals there was, in addition, a small amount of insulin antibody of 19S globulin type early during the immunization period.

The purpose in estimating a molecular weight equivalent of the insulin-antibody complex relates to the possibility that the distinctive features of the angiopathies of diabetes may depend upon certain physicochemical characteristics of this complex.
Electron Microscopy of the Pancreatic Islets of the Rat: Effects of Prolonged Insulin Injections
Authors: Logothetopoulos John
Published: December 2014

The electron microscopical changes of the pancreatic islets of rats were studied during the phase of transient diabetes and during recovery, following a prolonged period of insulin injections.

The most characteristic changes, besides the severe degranulation of the beta cells, were the “inactivity” of the Golgi complex and the absence of special spheroidal bodies from its vicinity. Evidence is presented that these satellite bodies may represent pregranules. Differences in the formation of granules in the Golgi area of the alpha, beta and acinar cell are illustrated and discussed.
Effect of Acute Muscular Exercise on Serum Immunoreactive Insulin Concentration
Authors: Cochran Burt , Marbach Edward P , Poucher Russell , Steinberg Terry , Gwinup Grant
Published: December 2014

The change in circulating levels of immunoreactive insulin (IRI) was studied in a group of six normal, three obese, and eight obese diabetic subjects undergoing the acute exercise of stair climbing. Bloods were sampled immediately before and after the exercise period. Serum IRI concentration decreased in ten subjects and did not increase in the remainder of the subjects. The data suggest an exercise metabolite rather than increased insulin secretion accounts for the enhanced glucose assimilation produced by muscular activity.
Reproducibility of the Oral Glucose Tolerance Test and the Rice-Meal Test in Mild Diabetics
Authors: Kosaka Kinori , Mizuno Yoshiatsu , Kuzuya Takeshi
Published: December 2014

Reproducibility of 100 gm. oral glucose tolerance test and of Sakaguchi's rice-meal test were studied in sixty untreated mild diabetic patients with fasting blood sugar below 140 mg. per 100 ml. (Hagedorn-Jensen method). The tests were performed twice within a one-week interval. There were considerable variations of blood sugar levels in the same individuals between the duplicate tests. Variations were of similar magnitude after glucose or rice-meal and were smaller for the fasting blood sugar. There was no positive relationship between blood sugar levels after loading and their variability. Such a relationship was, however, clearly demonstrated for the fasting blood sugar levels of 360 newly referred diabetics. Average blood sugar levels and standard deviations for each group remained very stable despite individual variability. Implications of the data on evaluation of the results of these oral tests are discussed.
Studies on the Perfused Rat Liver: I. Effects of Glucagon and Insulin on Glucose Metabolism
Authors: Williamson Joseph R , Garcia Antonio , Renold Albert E , Cahill George F
Published: December 2014

A method is described for perfusing the isolated rat liver with a solution of known composition without red blood cells, which also permits convenient monitoring of viability and function by measuring flow rate. The effects of insulin and glucagon were studied on urea synthesis, on glucose production and utilization, and on incorporation of glucose-U-C-14 label into Co2, protein, glycogen, total lipids, and fatty acids. Under the experimental conditions employed, the liver is capable of gluconeogenesis; however, it takes up and metabolizes about twice as much glucose as it releases. Glucagon increased glucose and urea production but markedly reduced incorporation of glucose-U-C-14 into Co2 and protein. The only statistically significant effect of insulin was to increase incorporation of label into fatty acids.
Experimental Diabetes in Pregnant Mice: Prevention of Congenital Malformations in Offspring by Insulin
Authors: Horii Kin-ichi , Watanabe Gen-ichi , Ingalls Theodore H
Published: December 2014

The main purpose of these experiments was the prevention of congenital malformations in offspring of alloxan-diabetic mice by insulin injections administered during pregnancy. The optimum dose of insulin and timing of its administration are described for mice made hyperglycemic by injection of alloxan of 80 mg. per kilogram of body weight.

Copulated female mice were given alloxan intravenously on the fourth day of gestation, followed by 0.4 units of Lente insulin every twelve hours beginning thirty to thirty-six hours after alloxan injection, and continuing until the sixteenth day of gestation. The control group was given only the alloxan injection on the fourth day of gestation. Pregnant mice were sacrificed on the nineteenth day of gestation; fetuses were removed by laparotomy and examined for external defects and skeletal deformities.

In fifty successful pregnancies treated with insulin, only one fetus (0.2 per cent) of 472 was malformed with a cleft palate; in fifty successful pregnancies given alloxan alone fourteen or 28 per cent of mice had one or more malformed fetuses. Altogether, twenty-two or 5.0 per cent of 437 fetuses in the latter group had malformations which included craniorhachischisis (seven fetuses), cleft palate (six fetuses), club foot (five fetuses), spina bifida, anencephalus, open eye, microphthalmia and skeletal deformities in one or more fetuses. The difference between the alloxan group and insulin treated group in the number of mothers having malformed fetuses, and in the number of malformed fetuses produced was statistically significant according to the chi-square test with a probability level of less than 0.01. In the alloxan group, increased body weight associated with advancing pregnancy was less advanced in mice having malformed fetuses than in those having normal fetuses. The foregoing tendency was also statistically significant with a probability level less than 0.01. However, no appreciable correlation was observed between the magnitude of hyperglycemia of mother mice and the frequency of fetuses with congenital malformations.
Combined Use of Regular and Crystalline Protamine (NPH) Insulins in the Treatment of Severe Diabetes
Authors: Oakley Wilfrid , Hill David , Oakley Nigel
Published: December 2014

The use of twice daily injections of regular and extended action insulin mixtures, originally described in 1937, is revived and Crystalline Protamine Insulin (NPH) is proposed as the most suitable extended action insulin at present available for use in conjunction with Regular Insulin.

It is suggested that, in severe diabetes, the physician should aim at achieving a blood glucose of below 150 mg. per 100 ml. before breakfast, lunch and supper, and at bed time. This standard of control has been sought in ten pregnant diabetics treated in hospital with twice daily injections of regular + NPH insulin mixtures, and blood sugar results are reported. Experience with the same regimen in 162 diabetic clinic outpatients is also described.

Practical aspects of treatment by twice daily Regular + NPH Insulin mixtures are discussed; it is concluded that this regimen provides a good, and probably the most widely applicable, method at present available for the treatment of severe diabetes. It is sometimes possible to omit one or more of the four insulin dose components of the regimen.
Glomerulosclerosis in the Long-term Alloxan Diabetic Monkey
Authors: Gibbs G E , Wilson R B , Gifford H
Published: December 2014

Diabetic glomerulosclerosis has been produced in alloxan diabetic monkeys maintained from one to four years with minimal insulin dosage and high carbohydrate diet. Cataracts and dwarfism also appeared. Present limited data suggest that increased dietary fat and insulin may ameliorate these developments.
Studies of the Metabolic Effects of Acute Insulin Deficiency: II. Changes in Hepatic Glycolytic and Krebs-Cycle Intermediates and Pyridine Nucleotides
Authors: Kalkhoff R K , Hornbrook K R , Burch H B , Kipnis D M
Published: December 2014

(1) Various glycolytic and Krebs-cycle intermediates and pyridine nucleotides were measured in the livers of anti-insulin serum treated (i.e., acute insulin deprivation) and alloxan diabetic rats (i.e., chronic insulin deprivation).

(2) Acute insulin deprivation of three-hour duration resulted in significant changes in the concentration profile of the various glycolytic intermediates suggesting marked impairment of glycolysis at the phosphofructokinase step, activation of glycogenolysis, and decreased hexosemonophosphate shunt activity. The tissue levels of citrate and malate were not elevated under these conditions.

(3) Insulin deficiency of forty-eight hours' duration produced changes in the hepatic levels of glycolytic and Krebs-cycle intermediates which differed in several important aspects with those seen in acute insulin deficiency. The accumulation of P-pyruvate and 3-P-glycerate in forty-eight hour alloxan diabetic rats, when gluconeogenesis is accelerated, suggests that the rate limiting step in this system resides at some step between the conversion of 3-P-glycerate and dihydroxyacetone-P.

(4) Acute insulin deficiency of three-hour duration produced no significant changes in the levels of oxidized and reduced pyridine nucleotides. Chronic insulin deficiency (48hr. alloxan diabetic rats) did not alter the content of TPN, TPNH or DPN but did cause a significant decrease (32 per cent) in the level of DPNH.
Gestational Blood Glucose Levels in Normal and Potentially Diabetic Women Related to the Birth Weight of Their Infants
Authors: O'Sullivan John B , Gellis Sydney S , Tenney Benjamin O , Mahan Clare M
Published: December 2014

Data from 5,534 prenatal registrants who had blood glucose determinations following the ingestion of 50 gm. of glucose indicated that age is the only maternal factor of significance to resulting blood glucose levels when other variables are held fixed.

The lack of a blood glucose—birth weight correlation in the general population was further explored with the demonstration that such a relationship exists among groups of potentially diabetic women.

Overweight women giving birth to a large baby were found to have significantly higher mean blood glucose values. The overweight women with an infant of average birth weight or the normal weight women with a large baby had no such blood glucose elevation. These data imply that more accurate separation of either the overweight women or women giving birth to large babies into groups of special significance to future development of diabetes mellitus is possible.
Lipoprotein Lipase Activity in Patients with Diabetes Mellitus, with and without Hyperlipemia
Authors: Jones Don P , Plotkin Gerald R , Arky Ronald A
Published: December 2014

No detectable abnormalities or changes in the post heparin plasma lipoprotein lipase (LPL) activity were found in fifteen “insulin independent” (stable) or sixteen “insulin dependent” (labile) diabetics, with or without hyperlipemia, in four patients with ketoacidosis and hyperlipemia both during the acute phase and after recovery, in two subjects with insulin induced hypoglycemia, and in two patients with gross hyperlipemia and diabetes during marked fluctuations in lipid levels in one, and during correction of the hyperlipemia in the other.

Abnormalities in the LPL system, as reflected in the post heparin plasma LPL activity, appear to play a minor role, if any, in the pathogenesis of diabetic hyperlipemia in man.
Hyperlipemia and Diabetes Mellitus
Authors: Bierman Edwin L , Amaral Jose A P , Belknap Benjamin H
Published: December 2014

Untreated alloxan diabetic rats developed marked hyperlipemia only when their diet contained fat. Diabetes had no effect on plasma triglyceride levels of rats fed a fat-free diet. This result, coupled with prior observations, suggests that hyperlipemia in alloxan diabetes in the rat, and perhaps in diabetes mellitus in man, is related to the intake of dietary fat.
Role of the Kidney in the Disposal of Radioiodinated and Nonradioiodinated Insulin in Dogs
Authors: Zaharko Daniel S , Beck Lyle V , Blankenbaker Ronald
Published: December 2014

Insulin concentration in each sample of dog urine, carotid artery plasma, or renal vein plasma was estimated following the infusion of bovine insulin-I-125, unlabeled bovine insulin, or glucose.

Insulin was estimated by immunoassay and by TCA insoluble radioactivity. Whenever insulin-I-125 and unlabeled insulin were infused together both methods were used on each sample.

In agreement with the conclusions of others, who have used less direct technics, it was found that the use of plasma TCA insoluble radioactivity to determine radio-insulin degradation in vivo results in an underestimate of insulin removal, and hence an overestimate of insulin half life. This finding was shown to apply not only to the whole animal but also to the kidney. All forms of insulin were removed by the kidney but the radioactive estimate of kidney insulin removal was less than that by immunoassay.

Data from experiments in which radioactive insulin was bound to guinea pig anti-insulin serum prior to infusion and from experiments in which ureteral ligation was performed prior to infusion indicated that the kidney removed insulin primarily by glomerular filtration but that direct absorption also played a role.
Comparison of Intravenous Glucose Tolerance and Intravenous Tolbutamide Response in Ischemic Cardiovascular Disease
Authors: Hagenfeldt Lars , Wahlberg Fredrik
Published: December 2014

The present investigation has shown a significant but weak correlation between the IVGT and the IVTR in patients with ischemic cardiovascular disease. For diagnostic purposes an adjustment of the criteria for IVTR given by Unger and Madison is suggested.
Method for the Isolation of Intact Islets of Langerhans from the Rat Pancreas
Authors: Lacy Paul E , Kostianovsky Mery
Published: December 2014

A simple method for the isolation of intact islets from the normal rat pancreas is described. The method is based upon disruption of the acinar parenchyma by injecting Hanks solution into the pancreatic duct system followed by incubation of the pancreas in collagenase. Islets can be separated rapidly from this mixture by sedimentation. The isolated islets release insulin in vitro and appear normal by light and electron microscopy after incubation. A centrifugation method is also described for isolation of large quantities of islets for biochemical studies.
Study of Familial Patterns of Reported Diabetes: Evaluation of Questionnaire Data
Authors: Klimt Christian R , Meinert Curtis L , Ho Irwin P , Briese Franklin W
Published: December 2014

This is a study, based on a family history survey for diabetes obtained by questionnaire from 31,046 students who entered the University of Minnesota during the five academic years from 1955–56 to 1959–60. For each individual reported in the questionnaire, the primary item of information obtained was the diabetes status, classified where possible according to parental mating group (i.e., both parents diabetic, one parent diabetic, neither parent diabetic).

The main purpose of the study, in the planning and initial operational stages, was to provide data adequate for testing the correlation of diabetes prevalence in offspring of parental mating groups with the number of diabetic parents and for testing single-gene genetic hypotheses. The initial data collected were on “reported diabetes”—a rather ill defined entity—and were besides, as became clear later, subject to some fairly gross errors of misclassification. The study plan included procedures for rectifying these difficulties, but it was not possible to carry this work through. As a consequence, it was felt that the data would not support the statistical analysis necessary to test the questions mentioned above.

There are, however, numerous familial patterns suggested by various tabulations of the data which, interpreted with caution, are of some interest. The following trends appearworth noting:

1. The average number of offspring per family does not appear to be correlated with mating subgroup, nor does it appear to be correlated with the presence of diabetes among first degree relatives.

2. Prevalence of diabetes appears to be positively correlated with the number of diabetic parents. In fact, the observed prevalence in families with one diabetic parent is about three times the prevalence in families with neither parent affected. This effect appears to persist even when the data are subclassified by parental age.

3. Mortality rates do not appear to be correlated with the number of diabetic parents. Sources of error inherent in the present study, in particular, and the retrospective questionnaire-based study, in general, are extensively analyzed and discussed.
Lipodystrophy A Variant of Lipoatrophic Diabetes
Authors: Steinberg Terry , Gwinup Grant
Published: December 2014

A patient with an unusual form of lipodystrophy is described. The sharp demarcation of the fatty and fat free areas at the L-2 L-3 dermatome junction was the striking feature of this case. This observation led to speculation that the pathogenesis of lipodystrophy might be related to a neurologic or neurohumoral abnormality. Plasma catecholamines and urinary catecholamine excretion rates were normal. Sweat analysis revealed greater sweat production in the fat-free areas. Studies of carbohydrate and lipid metabolism revealed similarities to the related disease, lipoatrophic diabetes. A careful review of the literature supported the concepts that in lipodystrophy the line of demarcation between fatty and fat-free areas always conforms to derma-tome junctions and that lipodystrophy should be considered an incomplete variant of lipoatrophic diabetes.
Prognosis of Proliferative Retinopathy in Juvenile Diabetics
Authors: Deckert T , Simonsen Sv E , Poulsen J E
Published: December 2014

Fifty-one mostly juvenile-onset diabetic patients with proliferative retinopathy without persistent proteinuria were observed for two to eighteen years (average six years) after proliferative retinopathy had been detected. At the end of five years 10 per cent had died, and about 50 per cent had become blind in both eyes (visual acuity 6/60 or less). Patients with localized, peripheral proliferations had better visual prognosis than patients with pre- or peripapillary proliferations. Hypercholesterolemia appeared to be a poor prognostic sign. It would appear on the basis of reported experience and the present investigation that a surgical procedure on the pituitary gland is a justified therapeutic attempt in juvenile diabetes with retinopathy consisting of either pre- or peripapillary or of widespread proliferations, provided that the patients have not already developed persistent proteinuria.
Effect of Free Fatty Acids and Insulin on Protein Synthesis and Amino Acid Metabolism of Isolated Rat Diaphragms
Authors: Buse Maria G , Buse John
Published: December 2014

The effect of free fatty acids and insulin on the incorporation of C-14 from amino acids into muscle proteins was studied in vitro using “cut” or “intact” rat diaphragms.

Insulin promoted the incorporation of C-14 from L-gly-cine-2-C-14, L-histidine-2-ring-C-14 and L-leucine-U-C-14 into muscle proteins. Insulin stimulated the uptake of 0.05 mM. leucine-U-C-14 from the medium, but not its oxidation to C-14-O2.

Palmitate (3 mM.) decreased the incorporation of C-14 from glycine and histidine into proteins of muscles stimulated with insulin. Octanoate (0.5-3 mM.) decreased the incorporation of C-14 from leucine into proteins. The inhibitory effect of octanoate on protein synthesis was demonstrated in the presence or absence of glucose and/or insulin. DL-β-hydroxybutyrate (15 mM.) decreased the incorporation of C-14 from leucine-U-C-14 into proteins in the presence of insulin.

Octanoate (1 mM.) stimulated the uptake of C-14 from leucine-U-C-14 from the medium and its oxidation to C-14-O2. DL-β-hydroxybutyrate (15 mM.) appeared to inhibit both processes, however; the latter may be due to isotope dilution.

The nonutilizable amino acid, α-aminoisobutyric acid-C-14, penetrated less readily into the intracellular water of diaphragms incubated with 1 mM. octanoate than into controls. However, since octanoate stimulated the uptake of C-14 from leucine from the medium it appears likely that octanoate inhibited the incorporation of C-14 from leucine into proteins at a step beyond amino acid transport.

It is suggested that FFA can influence amino acid metabolism in muscles and decelerate their incorporation into proteins. Limitation of protein synthesis in muscle by increased intracellular FFA may contribute to the supply of amino acids available for neoglucogenesis during stress and carbohydrate deprivation.
Effect of Diazoxide on Glucose U-C-14 Utilization in Mice
Authors: Jansen G R , Hutchison C F , Zanetti M E
Published: December 2014

(1) The effects of diazoxide on the conversion of oral doses of glucose-U-C-14 to fatty acids in adipose tissue, and to fatty acids and glycogen in liver have been studied in intact mice.

(2) Diazoxide in a subcutaneous dose of 10 mg. per kilogram inhibited conversion of the glucose-U-C-14 to fatty acids of epididymal fat approximately 50 per cent. The inhibition in conversion of isotopic glucose to fatty acids in liver was slightly less than that found for adipose tissue. These inhibitory effects as well as hyperglycemia occurred within twenty minutes after drug administration and ten minutes after the glucose-U-C-14 was given.

(3) In spite of the sensitivity of the system, insulin overcame the inhibitory effects of 200 mg. per kilogram diazoxide on all these parameters. This large dose of diazoxide did not antagonize the action of exogenous insulin.

(4) Although diazoxide inhibited conversion of glucose-U-C-14 to liver fatty acids, net incorporation into liver glycogen was stimulated one-hundredfold. A net increase in the weight of total liver glycogen also was found. The significance of the striking elevation in glycogen synthesis in terms of proposed mechanisms of action for diazoxide will be discussed.

(5) The inhibition in conversion of the glucose-U-C-14 to fatty acid and the hyperglycemia were accompanied by an increase rather than a decrease in the specific activity of the plasma glucose. This, combined with the fact that no antagonism to the action of exogenous insulin was observed, is consistent with the hypothesis that diazoxide-mediated hyperglycemia, at least at low doses, results primarily from an inhibition in insulin secretion. At higher doses adrenergic mechanism could also become involved in potentiating the hyperglycemia.
Effects of Ingestion of Long-chain and Medium-chain Triglycerides on Glucose Tolerance in Man
Authors: Tantibhedhyangkul Phienvit , Hashim Sami A , Itallie Theodore B Van
Published: December 2014

A mild hyperketonemia was induced in seven normal subjects by oral administration of a medium-chain tri-glyceride (MCT) composed of C8 and C10 fatty acids. One hour following MCT administration and during the period of hyperketonemia, an intravenous glucose tolerance test was performed on each subject. On other occasions, similar glucose tolerance tests were performed on the same subjects one hour following the ingestion of either water or corn oil. K values for the slopes of the disappearance curves following glucose administration were derived, and mean K values and their standard errors following water, corn oil, and MCT, respectively, were 1.80 ± 0.38; 2.64 ± 0.41; and 2.99 ± 0.89. Thus MCT-induced hyperketonemia did not inhibit the rate of disappearance of the intravenously given glucose.

The apparent enhancement of glucose tolerance after ingestion of the MCT and corn oil meals is not readily explained. It is possible that the presence of these fats in the, gastrointestinal tract promoted the secretion of certain beta-cytotropic enteric hormones. In addition, the mild hyperketonemia induced by the MCT may, of itself, have accelerated the rate of glucose disappearance by stimulating insulin production. Finally, the medium-chain fatty acids derived from MCT may have enhanced glucose tolerance by virtue of an inhibitory effect on hepatic-glucose output.
Influence of the Vagus Nerves on Pancreatic Insulin Secretion
Authors: Nelson Norman C , Blackard William G , Cocchiara John C , Labat Joseph A
Published: December 2014

The effect of short and long-term faradic stimulation of the vagus nerves on pancreatic immunoreactive insulin (IRI) release was assessed in dogs. In the present study stimulation of the vagus nerves at the level of the diaphragm or in the neck did not enhance pancreatic IRI release. The only significant effect was a transient fall in pancreatic vein IRI values immediately after stimulation was begun.
Who's Teaching the Diabetic?
Authors: Etzwiler Donnell D
Published: December 2014

Optimal management of diabetes mellitus minimizes or eliminates many of the serious accompanying complications. Proper control can be achieved only by well informed patients cooperating with interested and knowledgeable nurses, dietitians and physicians.Evaluation of the knowledge of diabetes among these groups of medical personnel was carried out by multiple-choice tests and follow-up studies of detection drives. Results indicate that lack of understanding of basic fundamentals of the disease among professional personnel may contribute to inadequate or ineffective patient education.
Beta Adrenergic Stimulation of Insulin Release in Man
Authors: Porte Daniel
Published: December 2014

Normal men and women were infused with the π-adrenergic receptor stimulator, isoproterenol (isopropylnorepinephrine, Isuprel). At a low dose (2 μg./min.), immunoreactive insulin (IRI) and free fatty acid (FFA) concentrations rose without a measurable change in plasma glucose. The rise in IRI was not blocked by pretreatment with nicotinic acid to prevent FFA mobilization by isoproterenol. Higher doses of isoproterenol (6 μg./min.) caused larger increments of IRI and FFA concentrations but also elevated plasma glucose. All effects of isoproterenol were the β-adrenergic receptor DlocKing agent y propranolol. Propranolol had no effect on glycogenolysis or IRI stimulation by glucagon. It is concluded that isoprotenol inereases IRI levll by direet seimnlation of β-adrenergic receptors. The ability of glucagon to stimulate the pancreatic islet and to elevate IRI appears to be mediated by a different mechanism.
Oral Glucose Tolerance Test in Siblings of Children with Diabetes Mellitus
Authors: Burkeholder James N , Pickens James M , Womack William N
Published: December 2014

1. Eighteen per cent of a group of 138 children who were given one or more glucose tolerance tests were classified as chemical diabetics.

2. One of the siblings who were classified as chemical diabetics later developed overt clinical diabetes, as did another child whose identical twin was a diabetic and whose blood sugar was abnormally low at three hours.

3. Five of nine children (56 per cent) in three families in which both parents had diabetic glucose tolerance tests had glucose tolerance tests which were sufficiently abnormal to classify them as chemical diabetics.
Changes of Individual Free Fatty Acids During Glucose Tolerance Test
Authors: Nakamura H , Faludi G , Spitzer J J
Published: December 2014

Regulation of individual FFA release from adipose tissue has been studied in control, obese and diabetic subjects in the course of glucose tolerance tests. Adipose tissue biopsies were also obtained from some of the subjects.

As in previous studies, fasting FFA levels were higher and the fall in FFA was greater in obese and diabetic subjects than in controls. There was a delay in both the fall and subsequent return of FFA.

With the decrease of FFA concentration, the contribution of palmitoleic, oleic, and linoleic acids to total FFA decreased, while that of myristic, palmitic and stearic acids increased. The opposite changes were observed as FFA levels rose.

Plotting the concentration of individual FFA against the corresponding total FFA level suggested linear regression of the individual FFA concentration on the total plasma FFA level in all three groups of subjects. The percentage contribution of the slope of each regression line to the sum total of the slopes was found to be very similar to the fatty acid composition of adipose tissue. This indicates that the release of individual FFA from adipose tissue is proportional to the total fatty acid composition of adipose tissue above FFA levels of about 200 μEq./L. or more. The existence of a “basal FFA level” is postulated (less than 200 μEq./L.) and a speculative consideration is presented indicating that the latter may be under the primary influence of factors other than adipose tissue.
Potentiation of the Tolbutamide Effect by Dicoumarol
Authors: Kristensen M , Hansen J Mølholm
Published: December 2014

The administration of dicoumarol to four elderly diabetics who were daily receiving 500 mg. tolbutamide led to an increase in the tolbutamide concentration in the blood associated with a fall in blood sugar. The accumulation of tolbutamide was due to an increase in the half-life of tolbutamide in the blood from the normal average of 4.9 hours to an average of 17.5 hours. The mechanism responsible for this increase may be inhibition of tolbutamide metabolism in the liver by dicoumarol.

This accumulation may well increase the risk of hypoglycemia, such as has been demonstrated after administration of sulfaphenazole to diabetic patients receiving tolbutamide.

Phenindione does not seem to have a similar effect and, accordingly, would appear to be preferable in anticoagulant therapy in diabetics receiving tolbutamide.
Effect of Dextran Sulfate on Plasma Lipoprotein Lipase Activity in Obese Subjects and Diabetic Patients
Authors: Shigeta Yukio , Nakamura Koji , Hoshi Mituru , Kim Minjern , Abe Hiroshi
Published: December 2014

The changes in plasma lipoprotein lipase activity after intravenous injection of dextran sulfate, which stimulates release of lipoprotein lipase, have been studied in forty two diabetic patients, eight obese subjects and eleven normal subjects.

In normal subjects, the response of lipoprotein lipase activity to dextran sulfate averaged 5.7±0.6 (S.E.) μEq. FFA/ml. at ten minutes and 6.5±1.2 (S.E.) μEq. FFA/ml. at twenty minutes.

A significantly decreased response of lipoprotein lipase activity to dextran sulfate was found in obese subjects and in diabetic patients, especially in those with hypertriglyceridemia. No correlation was observed between the cholesterol level and lipoprotein lipase activity. No significant relation between changes of lipoprotein lipase activity and the incidence of diabetic complications was found.
Ultrastructural Pancreatic Beta-Cell Changes in Rabbits After Small and Large Doses of Alloxan
Authors: Wellmann Klaus F , Volk Bruno W , Lazarus Sydney S
Published: December 2014

The effect of a single injection of alloxan monohydrate, varying in dosages from 12.5 to 200 mg./kg. body weight, on the ultrastructure of pancreatic β cells was investigated in 100 adult rabbits killed five minutes to fourteen days after alloxan administration.

Large doses of alloxan (50 to 200 mg./kg.) produced severe hyperglycemia due to marked β-cell damage characterized by translucent areas in the hyaloplasm, mitochondrial swelling, disintegration of the intercellular membrane, and nuclear pyknosis, followed by the dissolution of β- cell granules and, ultimately, disintegration of the cell. The sequence in which these changes occur suggests that alloxan, in high dosages, exerts its principal damaging action, at least initially, upon the paramembranous portion of the β-cell cytoplasm.

After small doses of alloxan, 12.5 or 25 mg./kg., hyperglycemia failed to occur. In these animals there was early degranulation, distension of the cisternae of the endoplasmic reticulum, variable dilatation of the profiles of the Golgi apparatus, and formation of morphologically atypical β-cell granules.

Small doses of alloxan, while not destroying the pancreatic β cells, alter the β-cell secretory apparatus sufficiently to induce subdiabetes, so that a normally nondiabetogenic dose of cortisone (1 mg./kg.) converts this state into one of overt diabetes. The ultrastructural and functional pancreatic β-cell changes after small doses of alloxan alone are quite similar to those induced by large doses of alloxan in cortisone-pretreated rabbits.
Ethanol-induced Hypoglycemia: II. Mechanism of Suppression of Hepatic Gluconeogenesis
Authors: Madison Leonard L , Lochner Amanda , Wulff Johan
Published: December 2014

The postulation that the increased NADH2/NAD ratio generated in the liver cell during ethanol metabolism causes the suppression of hepatic gluconeogenesis has been tested in several ways in twenty-eight fasted glycogendepleted dogs in whom hepatic gluconeogenesis was inhibited by infusions of ethanol. First, it was shown that fructose, a non-NAD-dependent precursor of glucose, produced a rapid restoration of hepatic glucose output during ethanol-induced suppression of hepatic gluconeogenesis. Second, in contrast, the infusion of glutamate and α-ketoglutarate, both NAD-dependent precursors of glucose, failed to augment the depressed rate of hepatic gluconeogenesis induced by ethanol. Finally, the administration of methylene blue, a redox dye which oxidizes NADH2 to NAD, not only prevented the expected fall in hepatic glucose output when infused simultaneously with ethanol, but also produced a rapid restoration of hepatic glucose output previously depressed by ethanol administration in fasting dogs. These data are consonant with the thesis that the increased NADH2/NAD ratio, which characterizes ethanol oxidation by the liver cell, causes a partial block at several points in the gluconeo genic pathway and is responsible for the ethanol-induced suppression of hepatic gluconeogenesis.