bluuebunny/crossref_metadata_2025 huggingface dataset:
A Semiautomated Technic for Radioimmunoassay: Double Antibody Assay of Insulin
Authors: Haas Melvyn L , Shenkman Louis , Weissman Peter , Andres Reubin
Published: December 2014

A semiautomated modification of the double antibody assay for immunoreactive insulin, using commercial equipment and easily constructed accessories, has been devised. It has been found to be a convenient and reliable method for performing insulin assay upon large numbers of samples.
Transplantation of a Pancreatic Insulinoma into an Insulin-resistant Patient with Juvenile Diabetes
Authors: Urea I , Kott I , Lev-Ran A
Published: December 2014

A case of juvenile diabetes who developed insulin resistance is presented. Despite insulin requirements of 300 U. a day his diabetes, of one-year duration, was inadequately controlled. On March 17, 1968 transplantation of a pancreatic insulinoma was performed. The tumor was excised from a fifty-three-year-old female patient suffering from hypoglycemic attacks and inserted beneath the fascia lata of the young patient. One week after the transplantation he was aglycosuric. Biopsy of the transplant three months later as well as biologic assess showed viable pancreatic tissue. Ten months after transplantation there was no biologic activity of the transplant; histology showed complete disappearance of pancreatic stroma with fibrous and cellular infiltration.

Despite these findings the patient feels well, works fully in the rural settlement and is controlled with 125 U. of Iletin (highly concentrated bovine insulin, 500 U. per 1 ml.) in one morning injection. It is not certain if the patient's improvement was due to the insulinoma or was coincidental.
Use of Growth Hormone as a Diabetic Stimulus in Man
Authors: Mitchell M L , Raben M S , Ernesti M
Published: December 2014

The diabetogenic potency of 10 mg. of human growth hormone and of 100 mg. of cortisone acetate was studied in five normal volunteers. Measurements of glucose, free fatty acids, immunoreactive insulin and immunoreactive growth hormone following a carbohydrate load revealed that twelve hours after a single intramuscular dose of growth hormone impairment of glucose tolerance and elevation in both serum insulin and free fatty acids were evident. Cortisone alone resulted in minimal changes in these indices, and the combination of cortisone and growth hormone was similar in effect to growth hormone alone. Concentrations of growth hormone in serum were still elevated twelve to fifteen hours after the intramuscular administration of a single 10 mg. dose.
Comparative Study of the Effects of Porcine Proinsulin and Insulin on Lipolysis and Glucose Oxidation in Rat Adipocytes
Authors: Toomey Richard E , Shaw Walter N , Reid Leroy R , Young Wilma K
Published: December 2014

Proinsulin blocked lipolysis activation by epinephrine, glucagon or theophylline. The antilipolytic effect of pro-insulin was not blocked by Kunitz pancreatic trypsin inhibitor (KPTI). The-concentrations of proinsulin and insulin required to cause 50 per cent inhibition of epinephrine-stimulated lipolysis were estimated to be approximately 1 × 10−9 M and 3 × 10−11 M respectively. Proinsulin which had been reduced and allowed to reoxidize was found to have approximately the same antilipolytic activity as native proinsulin, indicating that the antilipolytic effect was due to proinsulin and not insulin contamination. The concentrations of proinsulin and insulin required to give 50 per cent of maximal stimulation of glucose oxidation were estimated to be approximately 5 × 10−9 M and 1 × 10−11 M respectively. The effect of proinsulin on glucose oxidation did not appear to be caused by any insulin contamination since reduced-reoxidized proinsulin had approximately the same activity as native proinsulin. KPTI had no effect on proinsulin-stimulated glucose oxidation in isolated fat cells, in contrast to the marked inhibitory effect observed using intact epididymal fat pad. This suggests that the KPTI-sensitive proteolytic activity of the epididymal fat pad is not located in the fat cell but in some other type cell or extracellular space.
Studies of Insulin Secretion in the Perfused Rat Pancreas: Effect of Diazoxide and A025
Authors: Basabe Juan , Lopez Nestor , Viktora Josef , Wolff Frederick
Published: December 2014

Continuous glucose stimulation produces two phases of insulin secretion in the isolated perfused rat pancreas. Puromycin has no effect on the first phase but partially inhibits the second. The second phase has been reported previously to be associated in part with insulin synthesis.

In acute experiments, diazoxide and its derivative—A025—inhibit insulin secretion in both phases. This inhibition corresponds with an increase of the pancreatic tissue insulin content. These results suggest that both A025 and diazoxide decrease insulin release but have no effect on its synthesis.

In pancreatic perfusion of rats which had been chronically treated with diazoxide and A025 (per os), and who had been fasted and without drug for sixteen hours before the experiment, a greater insulin secretion was demonstrated in both phases compared with normal controls; however, if the perfusion is done three to four hours after the last dose, the amount of insulin secreted is smaller than the respective controls. This again suggests that during the period of action of the drug, pancreatic insulin is not released, but synthesis is not inhibited. The result, therefore, is an accumulation of insulin within the beta cells.

The acute and chronic experiments done under our experimental conditions in the perfused rat pancreas suggest that diazoxide and A025 inhibit insulin release, but have no effect on insulinogenesis.
Histopathologic Responses to Severe Alloxan Diabetes in Arteriosclerotic and Nonarteriosclerotic Rats
Authors: Wexler Bernard C
Published: December 2014

Male and female virgin rats having no arteriosclerosis and male and female breeder rats having established, naturally-occurring arteriosclerosis and relatively mild diabetes were given a single injection of alloxan which induced severe ketosis, hyperglycemia and hyperlipidemia. Animals were sacrificed one, two, three, four, five, six, and seven days, four and eight weeks after the onset of severe diabetes. Their livers showed prompt severe fatty metamorphosis and their islet beta cells total degranulation. After one week of untreated severe diabetes, the fatty infiltration of the liver became somewhat reduced as did the ketosis, hyperglycemia and hyperlipidemia. Concomitantly, the islets of Langerhans were greatly hypertrophied, the beta cells remaining degranulated. Male rats exhibited testicular atrophy and calcification; female rats manifested marked ovarian hypertrophy and corpora lutea formation. Many animals developed extensive areas of renal medullary necrosis. Approximately half of the animals of each group became emaciated with depleted islet beta cells; the remaining half had partially regranulated beta cells and were obese. The formerly nonarteriosclerotic virgin rats had developed microscopic arterial lesions, the emaciated and formerly arteriosclerotic breeder rats had developed extremely severe, calcific arteriosclerosis, but the obese, formerly arteriosclerotic breeder rats manifested very little evidence of arteriosclerosis indicating regression of arterial disease. It is concluded that partial restoration of insulin ameliorated while severe insulin deficiency caused acceleration and worsening of the arteriosclerosis in both the virgin and breeder rats and that the increased arteriosclerosis was due to the abnormal levels of glucose and lipid and to the effects of insulin deficiency on aortic metabolism per se.
Immunological Studies of the A and B Chains of Insulin
Authors: Touber Jan L , Stoll Ralph W , Ensinck John W , Williams Robert H
Published: December 2014

Radioimmunoassays for the measurement of the A and B chains of insulin were developed using antisera against S-sulfonated, oxidized and reduced derivatives of the chains. Antisera against S-sulfonated A chain were found to react with S-sulfonated A chain, but not with the oxidized or reduced A chain whereas antisera against the reduced or oxidized A chains reacted with all three (S-sulfonated, oxidized and reduced) A chain derivatives. Antisera against all three B chain derivatives reacted equally well with B chain preparations whether S-sulfonated, oxidized or reduced. Because of greater stability radioiodinated oxidized chain -preparations were employed in the assay rather than radioiodinated S-sulfonated chains.

Although the A and B chain immunoassays were specific for one or more antigenic sites on the A and B chain respectively, they were not specific for the chains alone since insulin, proinsulin, and convertible and nonconvertible fractions of proinsulin cross-reacted in both assays, especially in the B chain assay.

Plasma interfered in both assays in a nonspecific and nonuniform fashion. With this consideration, no evidence has been found that the chains of insulin were present in the: (1) plasma of fasted man, baboon and pig, (2) plasma of man and pig after oral glucose, (3) plasma of baboon and pig after intravenous insulin, or (4) perfusate of isolated rat liver after insulin administration.
Glucagon Potentiation of Insulin Secretion by the Perfused Rat Pancreas
Authors: Curry Donald L
Published: December 2014

The relationship between glucagon and insulin secretion was studied using the isolated perfused rat pancreas. Glucagon was found to have no stimulatory effect on the beta cells when glucose was absent from the perfusing medium. There invariably occurred, however, a substantial increase in the amount of insulin secreted (over and above that which was released in response to glucose alone) whenever glucagon and glucose were simultaneously administered to a pancreatic preparation. This potentiation of insulin release also occurred when tolbutamide was substituted, for glucose as the stimulatory agent, thus indicating that glucagon may be active on some end step in the secretory process rather than being mediated via a metabolite of glucose. The action of glucagon was also found to occur regardless of whether or not puromycin was present in the perfusate (at a concentration which has previously been shown to inhibit insulin synthesis), suggesting that a major action of glucagon is to augment the release of preformed insulin.
Effects of 2-Deoxy-D-Glucose on Insulin-Secretory Responses to Intravenous Glucose, Glucagon, Tolbutamide and Arginine in Man
Authors: Goldsmith Stanley J , Yalow Rosalyn S , Berson Solomon A
Published: December 2014

The effects of prior administration of 2-deoxy-D-glucose on insulin secretory responses to insulin secretagogues were studied. Following 2-deoxy-D-glucose administration to eight subjects including two maturity-onset diabetics, the stimulatory effects of both glucose and glucagon were markedly obtunded by comparison with control studies in the same subjects. In another group of eight subjects including one maturity-onset diabetic, the mean plasma insulin responses to tolbutamide and arginine were only very slightly but not significantly reduced following 2-deoxy-D-glucose as compared to control studies. These results suggest that the inhibitory effect of 2-deoxy-D-glucose on insulin secretory responses to glucose and glucagon is not related to epineplirine discharge and that the mechanism of stimulation of insulin secretion does not follow identical pathways for all secretagogues.
Mechanism of Epinephrine and Serotonin Inhibition of Insulin Release in the Golden Hamster in Vitro
Authors: Feldman Jerome M , Lebovitz Harold E
Published: December 2014

Similarities and differences in the mechanisms by which epinephrine and serotonin inhibit insulin secretion were studied in an in vitro golden hamster pancreas system. Both amines were shown to inhibit the insulin release stimulated by either high glucose (3 mg./ml.) or dibutyryl cyclic AMP 1 mg./ml. The beta adrenergic blocking agent propranolol had no effect on either basal or high glucose-stimulated insulin release. It also was without effect on the serotonin inhibition of high glucose-stimulated insulin release. Phentolamine, an alpha adrenergic blocking agent, prevented the serotonin inhibition of high glucose or dibutyryl cyclic AMP mediated insulin release. Phentolamine also blocked the action of epinephrine in inhibiting dibutyryl cyclic AMP mediated insulin release. The data indicate that both amines block insulin release by interfering with the action of 3′5′ cyclic AMP in causing insulin release. Phentolamine appears to act at the same locus, i.e., in the action of 3′5′ cyclic AMP. The only difference noted between serotonin and epinephrine action on the pancreatic beta cell was that methysergide maleate, a known serotonin antagonist, was able to block serotonin action but not that of epinephrine.
Effects of Hyperglycemia, Tolbutamide and Glucagon on the Pathways of Glucose Oxidation in the Goosefish Islet in Vitro
Authors: Hosteller Karl Y , Williams Hollis R
Published: December 2014

The contribution of the pentose and Krebs cycles to glucose metabolism has been determined in the isolated goosefish islet, in vitro, using glucose-2-C-14. Hyperglycemia caused increased net glucose metabolism by both the pentose and Krebs cycles, while glucagon and tolbutamide had no significant effect on net glucose metabolism by either pathway. The rate of reduced pyridine nucleotide formation was calculated and was increased with hyperglycemia but not with tolbutamide or glucagon.
Mode of Action of a Diazoxide Analog (A025): Its Effects on Insulin Secretion
Authors: Grant A M , Basabe J C , Lopez N L , Krees S V , Wolff F W
Published: December 2014

Studies of A025, an analog of diazoxide, have shown it to have hyperglycemic, but not antidiuretic, activity in rats and monkeys. A025 possesses some blood pressure-lowering activity. Catecholamine release did not appear to be involved in the hyperglycemic effect. A glucose-stimulated insulin release was inhibited in vivo by A025. Significant hyperglycemic activity was still present in adrenalectomized rats after A025 administration, whereas no hyperglycemic effect was produced by A025 in eviscerated rats. Daily administration of the compound was well tolerated by rats over a period of twelve weeks; glucose tolerance was reduced after six weeks; serum and pancreatic insulin were reduced when measured after nine weeks. Glucose tolerance was restored to normal three days after discontinuation of the drug. It is concluded that the primary mechanism ofhyper glycemia is insulin inhibition.
Diabetes in Central America
Authors: West Kelly M , Kalbfleisch John M
Published: December 2014

The prevalence of diabetes in Central America was somewhat greater than in East Pakistan and Malaya, less than in Uruguay and Venezuela, and substantially less than in affluent societies such as the United States. Differences in prevalence among Central American countries were modest but probably significant in some instances. In all Central American countries diabetes was more common in females but this difference was probably attributable to the greater adiposity of the women. Age-matched populations from eleven different countries of three continents have now been tested using standardized methods. Prevalenceof diabetes varied greatly, and differences were more related to environment than to race. These results support the hypothesis that environmental factors can increase or reduce prevalence by several-fold.
Ultrastructural Changes in B Cells of Pancreatic Islets from Rats with Elevated Levels of Circulating Growth Hormone Secreted by MtT-W15 Tumor
Authors: Bencosme Sergio A , Tsutsumi Victor , Martin Julio M , Åkerblom Hans K
Published: December 2014

The pancreatic B cells from rats bearing a growth hormone-producing tumor (MtT-W15) were studied by electron microscopy before and after incubation in media containing alternatively low (60 mg./100 ml.) and high (300 mg./ 100 ml.) glucose concentrations.

Tumor-bearing rats had been previously shown to have increased blood levels of somatotrophin and insulin and also to have B cells with increased responsiveness to in vitro glucose stimulation.

B cells from tumor-bearing rats, when compared with controls, showed (1) an increased number of secretory granules, (2) a marked increase in the proportion of pale to dark granules (30 to 60 per cent, as compared with 5 to 25 per cent for controls), and (3) the presence of numerous dilated cisternae of rough endoplasmic reticulum containing a flocculent material resembling the core of the pale granules. The last observation may indicate that pale secretory granules are formed in the endoplasmic reticulum of these hyperactive B cells. The fact that the hyperfunctioning B cells present in tumor-bearing rats possess a high number of pale granules suggests that these granules participate in the processes of insulin synthesis, storage, and secretion.

Pancreatic islets from control and tumor-bearing rats alternatively incubated in media with low and high glucose concentrations did not reveal significant morphological changes when compared with the nonincubated islets from the same animals. The extent of degeneration and necrosis observed in some B cells from control and tumor-bearing animals after incubation were unrelated to the glucose concentration in the incubation media.
Somatotrophin Action in Fatty Liver and Ketonemia in Pancreatectomized-Sympathectomized Dogs
Authors: Roldán Alicia G , Castillo E J del , Ashkar E , Rietti C T
Published: December 2014

Somatotrophin was injected (1 mg./kg./day) in pancreatectomized-sympathectomized and pancreatectomized-hypophysectomized dogs for two days. The results were compared with those in noninjected pancreatectomized, pancreatectomized-sympathectomized and pancreatectomized-hypophysectomized animals. It was found that (l)-hypophysectomy and sympathectomy decreased ketonemia and lipolysis [lower levels of plasma free fatty acids (FFA)] in diabetic pancreatectomized dogs and (2) somatotrophin increased plasma ketone bodies, FFA and total lipids in pancreatectomized-sympathectomized (those deprived of the sympathetic chains) and in pancreatectomized-hypophysectomized dogs.
Insulin Biosynthesis in Experimental Hereditary Diabetes
Authors: Poffenbarger Phillip L , Chick William L , Lavine Robert L , Soeldner J Stuart , Flewelling Judith H
Published: December 2014

Studies of proinsulin-insulin relationships were performed on serum and isolated pancreatic islets from normal (C57 BL/Ks) and spontaneously diabetic (CSlBL/Ks-dbdb) mice. The diabetic syndrome in these animals is inherited as an autO8omal recessive trait with complete penetrance and is characterized by the early development of obesity and hyperinsulinemia, followed by progressive hyperglycemia.

Gel nitration chromatography of diabetic mouse serum revealed that proinsulin comprised a relatively small proportion (9.6 per cent) of the total circulating insulin immunoreactivity.

Although diabetic mouse islets were enlarged, insulin content per islet was diminished, while proinsulin content per islet was similar to normal. Islet proinsulin:insulin ratios correlated sgnificantly with both blood glucose and serum insulin levels. This appeared to result from the fact that sustained hyperglycemia caused mainly a depletion of islet insulin, whereas proinsulin content remained unchanged, thereby increasing proinsulin:insulin ratios.

In vitro labeling experiments with H-3-leucine demonstrated no significant difference in the rate or pattern of incorporation of radioactivity into proinsulin and insulin fractions of normal and diabetic islets after 90 and 180 minutes of incubation.

Therefore, the apparent biological ineffectiveness of the high circulating levels of immunoreactive insulin in this diabetic syndrome did not appear to be the result of a disproportionate release of biologically less potent proinsulin, nor did there appear to be a detectable abnormality in proinsulin-insulin biosynthesis as assessed by these methods.
Immunoreactive Insulin in the Portal and the Peripheral Venous Blood after Intravenous Tolbutamide Administration
Authors: Erwald Rolf , Hed Ragnar , Nygren Arne , Röjdmark Sven , Sundblad Lars , Wiechel Karl-Ludvig
Published: December 2014

Immunoreactive insulin has been assayed in portal and peripheral venous blood in fourteen patients with hepatic, pancreatic and gastric disease before and after tolbutamide administration. The difference between portal and peripheral insulin varied considerably in different patients. In some of the patients the portal insulin seemed to increase at a time when peripheral venous insulin had started to decrease. The implication of this finding is discussed.
Sleep Release of Human Growth Hormone in Treated Juvenile Diabetics: Similarity to Normal Subjects and Nonsuppression by Hyperglycemia
Authors: Parker Donal C , Rossman Lawrence G
Published: December 2014

The effect of diabetic nocturnal hyperglycemia upon HGH release in sleep was studied in five insulin-treated, stable, nonobese juvenile diabetics on eleven nights and compared to mean release in thirteen normal young men. All were studied by sleep polygraphy. Samples were drawn every twenty minutes from indwelling venous catheters without disturbing sleep. HGH was measured by RIA and plasma glucose concentration by O-toluidine. Despite hyperglycemia of 195-382 mg. per 100 ml. on nine out of eleven nights at the time of sleep HGH peak, the repetitive nightly pattern of HGH release in diabetics resembled those of normals. The diabetic group's mean HGH concentration during sleep was 4.0 ± 0.6 ng./ml. (± S.E.) and mean peak sleep HGH concentration was 11.2 ±: 1.3 ng./ml., which were not signicantly different from those of normals (3.4 ± 0.3 and 12.5 ± 1.4 ng./ml. ± S.E. respectively). Thus, diabetic hyperglycemia, similar to constant glucose infusion hyperglycemia in normals, does not result in suppression of HGH release in sleep. This indicates that hyperglycemia is not an important regulator of rhythmical HGH release in sleep and suggests a primary neural character of this rhythm. HGH release in sleep was not enhanced in treated juvenile diabetes.
Carbohydrate-induced Hypertriglyceridemia: Inhibition by Phenformin
Authors: Owen W Crawford , Kreisberg Robert A , Siegal Alan M
Published: December 2014

The effect of phenformin on the induction of plasma triglyceride by high-carbohydrate feeding was studied in ten subjects (nine normals and one Type II, hyperlipoproteinemia). Each study was divided into four periods. During periods I and III, each subject received an American Diabetes Association diet calculated to maintain body weight and in periods II and IV a high-carbohydrate diet (85 per cent of the calories derived from carbohydrate) which was isocaloric with the control diet. Phenformin, 50 mg. twice daily, was administered in either period II or IV in association with the high-carbohydrate diet. There was no change in weight during the study. The plasma triglyceride increase (ΔTG) during the high-carbohydrate diet alone was 103 mg. per cent as compared with a ΔTG of 26 mg. per cent during the high carbohydrate-phenformin period, a highly significant difference (p < 0.005).

Insulin secretion and glucose tolerance during each period was determined by the sum of the increments above base baseline of plasma insulin and glucose concentrations during a five-hour oral glucose tolerance test. No significant differences in glucose tolerance or in insulin secretion occurred during any of the periods despite the alterations produced by the high-carbohydrate diet and phenformin in plasma triglyceride concentrations. A slight correlation could be demonstrated between the insulin response to a glucose load while on the control diet and the magnitude of the triglyceride response on the high-carbohydrate diet. The data indicate that (1) phenformin inhibits the induction of plasma triglyceride produced by carbohydrate loading, (2) there was no correlation between the changes in plasma triglyceride concentrations, glucose tolerance or insulin responsiveness during the experimental periods and (3) the magnitude of the increase in plasma triglyceride concentration may be related to the insulin response to a glucose load during the control period.
Diabetic Retinopathy: New Vessels Arising from the Optic Disc: II. Response to Pituitary Ablation by Yttrium 90 Implant
Authors: Panisset A , Kohner E M , Cheng H , Fraser T R
Published: December 2014

The response of new vessels arising from the optic disc to pituitary ablation was studied in sixty-six eyes of forty-five patients over six months to four years. The response was related to the extent of pituitary ablation graded as complete, intermediate or slight from endocrine tests done three months post-implant.

Following complete ablation there was a significant improvement in new vessels. A similar trend (but not significant values) was observed in partially ablated patients, while those with slight ablation showed no change.

Retinitis proliferans deteriorated in all groups, but least in those with complete and most in those with slight ablation. The mean visual acuity in the completely ablated group did not change, while it deteriorated significantly in the slight ablation category.

Patients under forty years of age at the time of the operation benefited more than those over forty.

It is concluded that new vessels on the disc respond to complete and intermediate pituitary ablation, complete ablation being superior in its effectiveness.
Glucose Tolerance and Insulin Secretion in Neonatal and Adult Mice
Authors: Lavine Robert L , Chick William L , Like Arthur A , Makdisi Thomas W
Published: December 2014

An ultramicro adaptation of the glucose oxidase method requiring only five microliters of blood was developed to study glucose tolerance of C57BL/Ks mice from one week of age through full maturity. Serum IRI levels were also determined ½ hour following intraperitoneal administration of glucose (2 mg./gm. body weight) and L-leucine (0.2 mg./gm. body weight). Glucose tolerance tests were performed by obtaining tail blood from fed mice immediately prior to (0 time) and 1/2, 1, 2 and 3 hours following intraperitoneal injection of 2 mg. glucose/gm. body weight. Results indicated that mean baseline (0 time) blood glucose levels were lowest in one-week-old mice (92 mg./100 ml. blood) and reached levels observed in adult animals by five weeks of age (142 mg./100 ml. blood). Despite the low baseline blood glucose at one week of age, these same animals exhibited marked and sustained hyperglycemia following glucose administration with mean levels of 469 mg./100 ml. blood and 401 mg./100 ml. blood at 1/2 and 3 hours, respectively. By two weeks of age glucose tolerance was improved ½ hour = 306 mg./100 ml. blood, 3 hours = 97 mg./100 ml. blood). By three weeks of age glucose tolerance curves appeared similar to those in adult animals. A significant difference between glucose tolerance in male and female mice was noted as early as eleven weeks of age. The marked glucose tolerance in one-week-old mice was explained, at least in part, by failure of these animals to show a significant rise in circulating serum IRI levels following glucose administration despite having the capability to secrete insulin in response to parenteral L-leucine.
Effect of Antilipolytic Compounds on Cyclic 3′, 5′-Adenosine Monophosphate Activation of Adipose Tissue Lipolysis
Authors: Schreibman Paul H , Wilson Dana E , Arky Ronald A
Published: December 2014

The lipolytic effect of cyclic 3′, 5′-adenosine monophosphate (cAMP) is inhibited by the beta-adrenergic blocker propranolol. This is demonstrated on both isolated fat cells and intact epididymal fat pad preparations. A cell-free extract of either rat or human adipose tissue contains a lipase system which can be activated by cAMP. This activation is also prevented by propranolol as well as the alpha-adrenergic blocker, phentolamine, in a dose-related fashion. Because of this nonspecific action, pharmacologic differentiation of alpha- or beta-adrenergic receptor sites should be based upon direct measurements of cyclic nucleotide, adenyl cyclase or phosphodiesterase, and not target enzyme activity.
Response to Intravenous Glucose in Juvenile Macaque Monkeys: Effect of Central Nervous System Lesions and Species Difference
Authors: Cornblath Marvin , Levitsky Lynne L , Kling Arthur
Published: December 2014

The influence of central nervous system lesions as well as species difference upon the response to a 0.5 gm./kg. intravenous glucose load has been evaluated in two primate species. The glucose, insulin, free fatty acids (FFA) and growth hormone response of four control M. mulatta did not differ significantly from that of three monkeys sustaining lesions of the amygdaloid nuclei or four animals with cortical lesions. However, glucose levels were lower and FFA levels higher in eight studies in six M. speciosa following cortical lesions compared to six control M. speciosa. The glucose disappearance rate (Kt) was significantly higher in the operated M. speciosa.

After intravenous glucose administration, the M. speciosa group had a significantly lower glucose response and a higher insulin response than did the M. mulatta. Free fatty acid levels were lower in control M. speciosa compared to M. mulatta, but higher in operated M. speciosa. Reserpinization or acclimatization to a primate chair did not alter the glucose and insulin response of M. mulatta.
Glucose Production from Fructose
Authors: Atwell Marshall E , Waterhouse Christine
Published: December 2014

Five adult subjects, three male and two female, were given fructose-U-C-14 by single injection under the condition of fructose loading. The radioactivity in glucose was determined in serial arterial samples. On a separate day, glucose-6-C-14 was given to these same subjects under identical conditions. Using these two curves, the fructose converted to glucose was determined. In these subjects an average of 30.94 per cent of the infused fructose appeared as blood glucose.

Hepatic vein catheterization showed a large positive arteriovenous difference for fructose (50 to 80 per cent of infused fructose) and negative arteriovenous differences for glucose and lactate. There was a discrepancy between the calculated fructose conversion to glucose (30 per cent) from the tracer studies and the glucose production estimated from the hepatic arteriovenous differences of glucose (10 per cent). Supporting data for the validity of the former figure are given.

The simultaneous hepatic production of glucose and lactate by the liver is most likely due to the large substrate load of fructose entering the glycolytic scheme at a point which bypasses the rate limiting enzymes for both glycolysis and gluconeogenesis.
Glucose Intolerance in Man During Prolonged Exposure to a Hypobaric-hyperoxic Environment
Authors: Love Lt Tommy L , Schnure Joel J , Larkin Edward C , Lipman Richard L , Lecocq Frank R
Published: December 2014

Eight subjects were exposed to a hypobaric (258 mm. Hg)-hyperoxic (100 per cent oxygen) environment for thirty days. Standard oral glucose tests were done during a control period of normal pressure and atmosphere, twenty-four hours after completing the thirty-day exposure and during a fifteen-day recovery. Exercise was uniform during the control period; however, during exposure and recovery periods four subjects continued daily exercise and the other four were maintained on limited activity (bedrest with bathroom privileges). Diet was constant throughout, containing 350 gm. of carbohydrates. Mean exposure period fasting (104.5 ± 6.5 mg./100 ml. S.E.M.) and sixty-minute (145 ± 18.5 mg./100. ml.) glucose values were significantly greater than corresponding control period fasting (87.1 ± 1.6 mg./ 100 ml.) and sixty-minute (105 ± 4.6 mg./100 ml.) control values. Mean plasma glucose values at 120 and 180 minutes during exposure to the test atmosphere were greater, but not significantly different than during control periods. Results of the glucose tolerance tests done fifteen days postexposure showed mean fasting 60-, 120- and 180-minute values to be significantly higher than the pre-exposure controls but similar to the exposure values. Serum immunoreactive insulin concentrations immediately after exposure and during recovery were unchanged from control levels. No difference in either glucose or insulin values could be detected between the exercise and nonexercise groups. It is suggested that prolonged exposure to hypobaric-hyperoxic environments adversely influences glucose tolerance.
Sensitivity and Specificity of Five Screening Tests for Diabetes in Ten Countries
Authors: West Kelly M , Kalbfleisch John M
Published: December 2014

The sensitivity and specificity of each of five screening tests were estimated in each of three to ten countries by testing subjects drawn from the general populations of adults over thirty-four years of age. This permitted comparisons among countries and among the different tests (fasting, postprandial, and postglucose urine tests, and fasting and postprandial blood glucose values).

Sensitivity and specificity of each test varied widely among populations. For example, the sensitivity of the twohour urine glucose ranged from 17 per cent in Nicaragua to 100 per cent in East Pakistan. Apparently specificity and sensitivity of such tests are influenced by many factors including both the circumstances under which the tests are performed and the characteristics of the population tested. It is, therefore, not possible to predict prevalence rates reliably by extrapolating from the results of screening tests. However, we believe the data for specific populations on the sensitivity and specificity of various tests will provide a rough guide in predicting the cost-effectiveness of alternative approaches to case detection in those particular countries. For instance, these results suggest that roughly 56 per cent of the occult diabetics in Costa Rica in this age group would be detected by a two-hour urine glucose, but only about 41 per cent of those in whom this test was positive would prove to have diabetes.

Even modest changes of criteria in defining either “diabetes” or Department of Medicine, University of Oklahoma School of Medicine, Oklahoma City, Oklahoma 73104.“abnormality” of the screening results produced marked changes in rates of sensitivity and specificity. With few exceptions, tests which were more sensitive were, comparably, less specific, and the reverse was also true. Rates of “diabetes” were markedly influenced by modest changes in diagnostic criteria.
Quantitative Measurements of Skin Capillary Resistance in Hypophysectomized Long-term Diabetics
Authors: Christensen Niels Juel , Terkildsen Anne Birgitte
Published: December 2014

Quantitative measurements of skin capillary resistance were carried out in twelve control subjects, eight long-term diabetics with proliferative retinopathy, and in sixteen diabetics hypophysectomized for diabetic retinopathy. Ten individual measurements of capillary resistance were performed on each subject. All subjects but two were less than fifty years of age.

In the control subjects, the mean capillary resistance ranged from 144 to 222 mm. Hg. With the exception of two, all had mean values between 150 and 200 mm. Hg.

The long-term, nonoperated patients demonstrated fragile capillaries. All but one of these patients had mean values below 150 mm. Hg (range 90 to 160 mm. Hg). Most of the hypophysectomized diabetics had a mean capillary resistance above 200 mm. Hg (range 162 to 372 mm. Hg). The values were significantly increased in comparison with the results obtained in the control subjects and in the nonoperated diabetics.
Differential Plasma Insulin Response to Glucose and Glucagon Stimulation Following Ethanol Priming
Authors: Friedenberg Ralph , Metz Robert , Mako Mary , Surmaczynska Barbara
Published: December 2014

The early phase of the insulin secretory response to glucose may not be derived from the total pool of stored insulin, but possibly from a specific and relatively small fraction in a state or locus necessary for its immediate release. In an attempt to deplete this hypothetical fraction, and thereby to support the concept of its existence and obtain an estimate of its size under different circumstances, normal and mildly diabetic subjects were given a series of three large glucose loads followed by glucagon, with and without alcohol “priming”. Results indicate that repetitive glucose or glucagon challenges over a two-hour period failed to exhaust the supply of immediately releasable insulin in either group of subjects as judged by the increments in plasma insulin during the first few minutes after each challenge. Alcohol pretreatment resulted in a larger early insulin secretory response to the first of three glucose loads, but a decreasing response to the subsequent two, possibly indicating that the initially augmented secretory response had resulted in depletion of a finite supply of immediately available insulin. An unexpected finding was the inhibitory effect of alcohol on glucagon-induced insulin release, in direct contrast to its effect when glucose is the insulinogogue, suggesting that glucose and glucagon exert their effects throughdifferent mechanisms or on different fractions of the insulin pool.
Is there a Delay in the Plasma Insulin Response of Patients with Chemical Diabetes Mellitus?
Authors: Reaven G M , Shen S W , Silvers A , Farquhar J W
Published: December 2014

We have compared the plasma glucose and immunoreactive insulin responses to oral glucose, intravenous glucose and intravenous tolbutamide of twenty normal subjects with those of eleven patients with chemical diabetes. The two groups were similar in terms of age, sex and degree of adiposity. The insulin response of patients with chemical diabetes was greater at every time interval during all these tests. Thus, we could document no defect in the rapidity of insulin response to these stimuli in patients with chemical diabetes. These results do not support the view that the commonest metabolic abnormality in patients with diabetes is a delay in the insulin response.
Antipancreatic Cellular Hypersensitivity in Diabetes Mellitus
Authors: Nerup Jørn , Andersen Ole Ortved , Bendixen Gunnar , Egeberg Jørn , Poulsen Jacob E
Published: December 2014

The occurrence of organ-specific, cellular hypersensitivity against pancreatic components was examined in twenty-two diabetics by means of the leucocyte migration test. An extract was prepared from pooled porcine pancreatic glands, in which atrophy of the exocrine tissue had been induced by ligation of the pancreatic duct. A specifically altered in vitro reactivity to the pancreatic preparation, consistent with a state of organ-specific, cellular hypersensitivity, was demonstrated in the diabetic group as compared to a control group. Intracutaneous injection of the same preparation in six diabetics with a positive in vitro reaction induced a typical delayed type reaction in four.
Reactive Hypoglycemia in Women: Results of a Health Survey
Authors: Jung Y , Khurana R C , Corredor D G , Hastillo A , Lain R F , Patrick D , Turkeltaub P , Danowski T S
Published: December 2014

1. Reactive hypoglycemia (for the purpose of this evaluation: blood glucose levels of 59 mg. per 100 ml. or less at the second, third, fourth or fifth hours of an oral glucose tolerance test) occurred in about 17 per cent of a group of 285 adult females participating in a survey.

2. This degree of reactive hypoglycemia occurred more often in the younger members (twenty to forty-five years of age), i.e., in 19 per cent of those with body weight less than 146 lbs. and in 31 per cent of those whose weight was above this range. Hypoglycemia was distinctly less frequent in the older nonoverweight females (2 per cent) and in the older obese group (11 per cent).

3. The lesser frequency of this degree of reactive hypoglycemia in the older nonobese and obese groups is attributable to higher fasting levels of glucose and to greater increments in blood glucose levels following upon an oral glucose load and not to any decrease in the usual increments in insulin.

4. In the two younger groups (twenty to forty-five years of age and either less than 146 lbs. or 146 lbs. or more in weight), those with reactive hypoglycemia as defined above had lower fasting blood glucose levels. This fact alone accounted for the subsequent occurrence of hypoglycemia. This conclusion is supported by the finding that the responses of those with and those without the stated degree of hypoglycemiaare Indistinguishable in terms of increments in blood glueose increments in insulin, and in the rations of the two.

5. Our data permit the generalization that blood glucose levels between 59 and 41 mg. per 100 ml. in the later hours of an oral glucose tolerance test are so common in young individuals, nonobese and obese, that this must be taken into account in any evaluation of so-called functional or reactive hypoglycemia in persons of this age. This degree of hypoglycemia is much less frequent in persons above forty-five of age.
Insulin Secretion Studied in the Perfused Rat Pancreas: II. Effect of Glucose, Glucagon, 3'5' Adenosine Monophosphate, Theophylline, Imidazole and Phenoxybenzamine; Their Interaction with Diazoxide
Authors: Basabe J C , Lopez N L , Viktora J K , Wolff F W , McNeal B , Mongelli C , WcInhardt K , Baukal A
Published: December 2014

This communication reports studies dealing with the action of glucagon, theophylline, cyclic adenosine monophosphate (3′5′.AMP) and phenoxybenzamine on insulin secretion, and their possible interaction with glucose and diazoxide.

Diazoxide inhibited both phases of insulin secretion produced by glucose. This blocking action was suppressed when the alpha-blocking phenoxybenzamine was present.

Glucagon produced a uniform pattern of insulin secretion when perfused alone. A one-minute pulse of 3′5′.AMP produced a sharp peak of insulin secretion. Neither glucagon nor 3′5′.AMP effects were inhibited by diazoxide.

Theophylline did not increase the basal insulin-secretion. However, when perfused together with glucose, theophylline stimulated additional insulin secretion, significantly higher than that produced by glucose alone.

When combinations of glucagon plus glucose, 3′5′.AMP plus glucose and theophylline plus glucose, were perfused, diazoxide blocked the secretion of insulin stimulated by glucose, but not that produced by glucagon, 3′5′.AMP or theophylline. This suggests that glucagon, 3′5′.AMP and theophylline stimulate insulin secretion by actingon mechanismsdifferent from the ones stimulated by glucose
Capillary Blood Sugar Values in Children During the Oral Cortisone-Primed Glucose Tolerance Test
Authors: Cole Harold S , Bilder Joan H , Epel Rosa
Published: December 2014

Three-hour oral cortisone-primed glucose tolerance tests were performed on a total of 113 children in three age groups; 1½ to less than 4 yrs., 4 yrs. to less than 8 yrs., and 8 to 12 yrs. of age. All children had negative family histories for diabetes, were in good health, and had recent normal oral glucose tolerance tests. A capillary blood micro-technic for blood sugar was used. Oral glucose was administered according to age and weight. The total cortisone dosage was 280 mg. per M2 given in two equally divided doses eight-and-one-half and two hours before the testing.

It is suggested that the blood sugar values for the 1½ to less than 4 yrs. age group be considered separately because of significant differences from the other age groups. The values for the ± 2 standard deviation range for boys and girls from 4 to 12 yrs. of age were: fasting (54.4–114.0 mg./100 ml.); 30 min. (96.1–202.9 mg./100 ml.); 60 min. (74.7–202.3 mg./100 ml.); 90 min. (72.5–169.3 mg./100 ml.); 120 min. (65.8–157.4 mg./100 ml.) ; 180 min. (49.6–122.4 mg./100 ml.).
A Treatment for Insulin-induced Fat Atrophy
Authors: Watson B M , Calder J S
Published: December 2014

Neutral insulin and biphasic insulin have been used in the past five years in seven patients suffering from localized subcutaneous fat atrophy as a complication of the injection of other insulin preparations. In all cases marked improvement of the atrophy occurred.
Effect of 2-Deoxy-D-Glucose and Mannoheptulose on the Insulin Response to Amino Acids in Rabbits
Authors: Lucke Christoph , Kagan Avir , Adelman Neil , Glick Seymour M
Published: December 2014

Plasma insulin levels were measured in rabbits in response to the administration of leucine and of arginine. Suppression of the amino-acid-induced insulin secretion by pretreatment with mannoheptulose and with 2-deoxy-D-glucose was attempted. The insulin response to leucine was suppressed to about 50 per cent of control values by both mannoheptulose and 2-deoxy-D-glucose. The response to arginine was not significantly altered by 2-deoxy-D-glucose hut was suppressed to 27 per cent of control values by mannoheptulose. The data suggest that (1) substances interfering with glycolysis can suppress amino-acid-induced insulin release and (2) arginine and leucine cause insulin secretion by different mechanisms.
Studies of Adenosine and Dibutyryl Adenosine 3'5'-Monophosphoric Acid on the Isolated Fat Cell
Authors: Solomon Solomon S , Kitabchi Abbas E
Published: December 2014

The action of adenosine 3',5'-monophosphate (c-AMP) and N6, O2'-dibutyryl adenosine 3',5'-monophosphate (dc- AMP) was studied in isolated rat adipocytes using parameters of glucose oxidation and lipolysis. Whereas c-AMP stimulated the conversion of glucose-U-C-14 or glucose-1-C-14 to C-14-O2, dc-AMP inhibited C-14-O2 production below the baseline in each case. Both N6-monobutyryl adenosine 3',5'-monophosphate (N6 mbc-AMP) and O2'-monobutyryl-adenosine 3',5'-monophosphate (O2'-mbc-AMP) stimulated C-14-O2 production from glucose-U-C-14. Only N6-mbc-AMP, however, was significantly lipolytic. When glucose-6-C-14 was utilized as the substrate, both c-AMP and dc-AMP stimulated its conversion to C-14-O2.

Dibutyryl cyclic AMP antagonized the action of insulin and proinsulin on glucose-U-C-14 oxidation in the isolated fat cell by an apparent competitive mechanism. Paradoxically, insulin potentiated C-14-O2 production from glucose-6-C-14. in the presence of 1.0 mM dc-AMP. C-AMP exhibited no such response.

It is concluded that under the experimental conditions described, (1) c-AMP and dc-AMP exhibit divergent effects with regard to glucose oxidation; (2) by the use of glucose-U-C-14 and glucose-l-C-14, dc-AMP competitively inhibits the action of insulin or proinsulin on glucose oxidation; (3) insulin synergistically stimulates C-14-O2 production from glucose-6-C-14, in the presence of dc-AMP; and (4) both N6- and O2'-butyrate moieties are necessary for the inhibitory effect on glucose oxidation observed with dc-AMP.
Fine Structure of the Endocrine Pancreas in Newborn Rodents
Authors: Boquist Lennart
Published: December 2014

The pancreases of one to ten day old mice, Chinese hamters and Mongolian gerbils were examined by electron microscopy. Any essential species or sex differences were not recorded. In the ductules there were endocrine cells, sometimes reaching the lumen. Endocrine cells were also seen in buds on the ductules. Mitosis occurred in acinar, centroacinar, ductule, A—, B—, and capillary endothelial cells. The ductule cells exhibited cilia and signs of ceritriole replication. The various islet parenchymal cell types could be differentiated in all animals. Other findings were perinuclear fibril bundles, structural variation of the secretory granules, dilated intercellular spaces and signs of emiocytosis.

The results indicate that in the species investigated, new formation of endocrine cells occurs in the neonatal period both by proliferation and development of endocrine cells from the ductules and by mitotic division of the islet parenchymal cells. No morphologically detectable lesions were found in the islets of newborns of the Chinese hamster which has a hereditary trait for the development of diabetes mellitus.