bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies in Patients with Chlorpropamide-Induced Hypoglycemia
Authors: Frey Harald M M , Rosenlund Bent , Sandtrö K
Published: December 2014

Six patients with hypoglycemia due to chlorpropamide are reported. The common characteristics were old age and/or poor nutritional state.

The serum concentration of chlorpropamide during hypoglycemia was not higher than that seen in a group of chlorpropamide-treated diabetics without hypoglycemia. In both groups, the serum level declined in a rectilinear fashion after the drug was stopped, and the rate of decline was similar in the two groups. The serum level of chlorpropamide in the control group covered a fourfold range at the same dose level, and had no correlation with the degree of diabetic control.

The serum insulin concentration was in two instances somewhat high compared to the low blood sugar, but most of the time was found to be at a low (fasting) level. In three patients no evidence of insulin secretion in peripheral venous blood was found even after stimulation with glucagon, glucose, or meals. In two of them, however, the absence of insulin was transient and present only during the day of hypoglycemia.

It is suggested that diabetics in negative calorie balance are predisposed to hypoglycemia ifthey continue to take chlorpropamide, and that they suffer this complication even with a serum concentration of the drug that is within therapeutic range. The pathogenesis probably does not involve increased peripheral utilization of glucose, but more probably an inhibiting effect on production of glucose by the liver.
Synergistic Effect of Certain Amino Acid Pairs upon Insulin Secretion in Man
Authors: Floyd John C , Fajans Stefan S , Pek Sumer , Thiffault Charles A , Knopf Ralph F , Conn Jerome W
Published: December 2014

Individual amino acids were administered intravenously in amounts of 15 gm. and again together with 15 gm. of a second amino acid as 30-gm. mixtures. Synergism in the stimulation of the release of insulin was demonstrated when the sum of the increases in plasma insulin which resulted from the separate infusions of two amino acids was exceeded by that obtained when they were administered as a mixture. A synergistic effect was exerted by arginine and leucine, arginine and phenylalanine, but not by arginine and lysine, arginine and histidine, or by leucine and histidine. Synergism was greater with arginine and leucine than with arginine and phenylalanine. It appears to result from the effects of these amino acid pairs upon the pancreatic beta cell.
Antilipolytic Effect of Porcine Proinsulin
Authors: Steele Ann A , Brown Joseph D , Stone Daniel B
Published: December 2014

Shaw and Chance have recently demonstrated that Kunitz pancreatic trypsin inhibitor (KPTI) blocks the increased conversion of labeled glucose to carbon dioxide and fatty acids in normal adipose tissue of rats in the presence of porcine proinsulin. The experiments reported here were designed to observe the antilipolytic effect of insulin and porcine proinsulin on lipolysis induced by epinephrine and glucagon in isolated fat cells and intact fat pads from rats, both in the presence and absence of KPTI and soybean trypsin inhibitor.

It was found that both insulin and proinsulin are potent inhibitors of lipolysis induced by DL-arterenol and by glucagon. Neither KPTI nor soybean trypsin inhibitor blocked the antilipolytic effect of insulin or proinsulin when lipolysis was stimulated by DL-arterenol or by glucagon. The failure of KPTI to inhibit the antilipolytic effect of proinsulin on isolated fat cells may have been caused by inactivation of KPTI by collagenase used in preparation of the isolated fat cells. To test this hypothesis experiments were performed using intact fat pads. As with the isolated fat cells, KPTI did not inhibit the antilipolytic effect of insulin or proinsulin.

These observations indicate that, in isolated fat cells and intact fat pads of the rat, proinsulin itself is an effective antilipolytic agent.
Capillary Blood Sugar Values in Infants and Children During Oral Glucose Tolerance Tests
Authors: Cole Harold S , Bilder Joan H
Published: December 2014

A capillary blood micro technic for blood sugar utilizing the Unopette, a device forobtaining the required specimens, is described. The accuracy of the Unopette was tested and established.

Three-hour capillary blood oral glucose tolerance tests, using this methodology, were performed on a total of 159 children in three age groups; one week to one-and-one-half years, one-and-one-half to three years, and three to twelve years. Oral glucose solution was administered according to age and weight. All children had negative family histories for diabetes and were in good health. The mean blood sugar values for each of the three age groups were compared with one another for each of the sampling periods. No significant differences at the 5 per cent level were observed among the group means at any of the six testing periods. Over-all means and the values of ± 2 standard deviations and the third to ninety-seventh percentiles were determined for the three age groups combined. Values for the :± 2 standard deviation range were: Fasting (55 to 88 mg./ 100 ml.); thirty minutes (77 to 160 mg./100 ml.); sixty minutes (66 to 149 mg./100 ml.); ninety minutes (68 to 133 mg./100 ml.); 120 minutes (59 to 130 mg./100 ml.); 180 minutes (46 to 105 mg./100 ml.).
Pancreatic Insulin Secretion Following Intrapancreatic Infusion of Amino Acid
Authors: Colwell A R , Zuckerman L , Berger S
Published: December 2014

Both protein ingestion and amino acid infusion are known to stimulate insulin secretion. The mechanism of this response has been attributed to increased plasma amino acid concentration. The present studies were undertaken to determine whether this-secretory response is due to a direct effect of amino acids on the islet cells or whether it is mediated through some other indirect mechanism. Accordingly, pancreatic infusion studies were conducted to help resolve this question.

Casein hydrolysate (1 gm.) infused into the pancreatico-duodenal artery of dogs for one-half hour provoked an immediate secretion of insulin into the portal vein. Femoral arterial insulin concentration also rose within five minutes, although hyperglycemia was not observed until the end of the infusion. An insulin response of similar magnitude was achieved by pancreatic glucose infusion (1 gm.). Simultaneous administration of epinephrine (30 μg.) inhibited the insulin responses to both glucose and amino acid. Combined infusion of casein hydrolysate and glucose (0.5 gm. each) produced a greater insulin response than the sum of the individual responses, suggesting glucose-amino acid synergism. Intraportal infusion of casein hydrolysate produced no significant insulin response in either portal venous or femoral arterial plasma.

These studies suggest that the insulin response associated with ingested or parenteral protein represents a direct amino acid effect on the islets of Langerhans. They also suggest that the amino acid concentration in the pancreas may be as important as glucose in control of insulin secretion.
Plasma Zinc and Copper in Diabetes Mellitus
Authors: Pidduck Heather G , Wren Peter J J , Price Evans David A
Published: December 2014

A review of the literature indicated some disagreement concerning plasma zinc levels in diabetes mellitus. Diabetics of both sexes with all degrees of severity of the disease have been studied and compared with controls matched for age and sex. Plasma zinc estimations were performed using a simple dilution method and atomic absorption spectrophotometry. Copper analyses were also carried out by a similar procedure. The results show that there are no significant differences in the nonfasting plasma zinc and copper levels between diabetics and controls.
Biochemistry of Extrapancreatic Tumor Hypoglycemia
Authors: Kreisberg Robert A , Hershman Jerome M , Spenney Jerry G , Boshell Buris R , Pennington Lloyd F
Published: December 2014

To define the biochemistry of tumor hypoglycemia, the metabolism of glucose and lactate were investigated in a patient with hypoglycemia associated with an adrenocortical carcinoma. Glucose and lactate kinetics and interconversion were determined by a primed-infusion technic in which 100 μc. each of glucose-1 and L-(+) lactate-U-C-14 were administered over a four-hour period on successive days before and after removal of the tumor. Before removal of the tumor, 400 gm. of glucose per day were required to maintain normoglycemia. Glucose turnover and its conversion to lactate were increased to values that were two to three times those observed in five normal subjects studied by these technics. Glucose oxidation and its contribution to the fuel of respiration were also enhanced. Although all aspects of glucose metabolism were quantitatively increased, no single route of glucose disposal was responsible for the accelerated turnover, and the pattern of metabolism was qualitatively normal. Despite excessive cortisol production, endogenous glucose production was paradoxically suppressed to 20 per cent of normal, and lactate incorporation into glucose was inhibited. Plasma free fatty acid concentrations were normal but did not respond to the administration of epinephrine. Following surgery, the hypoglycemia disappeared, glucose and lactate turnover returned to normal, and gluconeogenesis from lactate increased. Immunoreactive insulin and insulin-like activity in the plasma were not increased and extracts of the tumor did not produce hypoglycemia when injected into mice.

The hypoglycemia in this patient was due to a combination of increased glucose utilization and decreased glucose production. The data are consistent with the concept that these tumors synthesize and release a substance, which is currently unidentified, which acts on peripheral tissues and liver in a manner similar to insulin but which is undetectable by immuno- and bioassay technics.
Differential Effect of Porcine Proinsulin on Rat Epididymal Fat Cells and Fat Pieces
Authors: Challoner David R , Yu Pao-lo
Published: December 2014

Proinsulin is a biosynthetic precursor of insulin which reacts with insulin antibody and has been found in the peripheral circulation. The present studies were undertaken to determine the extent of its intrinsic biologic activity as compared with insulin and to provide evidence regarding the possibility and anatomic location of its conversion to insulin or biologically active related products in peripheral tissues.

The effects of single component porcine insulin and proinsulin on the conversion of glucose-l-C-14 to C-14-O2 and inhibition of the theophylline-stimulated lipolysis were studied in rat adipose tissue cells and pieces. Kunitz pancreatic trypsin inhibitor (KPTI) was used to block tissue conversion of proinsulin to insulin. Proinsulin was twentythree to twenty-seven times less effective than insulin when assayed on isolated fat cells. These results were not changed significantly by KPTI. Whereas insulin appeared less effective on fat pieces than on cells—presumably due to difficulty with diffusion into the more intact tissue—proinsulin, an even larger molecule, was as effective in fat pieces as fat cells. Thus proinsulin was only nine to eighteen times less effective than insulin when assayed on fat pieces. With KPTI, fat pieces became markedly insensitive but still responsive to proinsulin.

These results suggest that the proinsulin molecule has biologic activity not necessitating conversion to insulin for expression. Intact tissues contain trypsin-like activity capable of converting proinsulin to insulin. This activity must be located between the vascular endothelium and before access to, but not including, the cell membrane.
Insulin Response in Pancreatectomized Dogs Treated with Oxytetracycline
Authors: Hiatt Nathan , Bonorris George
Published: December 2014

Treatment with dxytetracycline seems to prolong and intensify the activity of insulin administered to pancreatectomized dogs. Oxytetracycline-treated dogs can be kept normoglycemic with small doses of insulin, have nondiabetic glucose tolerance, and exhibit the impaired hyperglycemic and cardiac responses to epinephrine of normal animals treated with insulin.
Fatal Systemic Candidiasis Following Treatment of Addisonian Crisis in a Juvenile Diabetic
Authors: Podolsky Stephen , Ferguson B Dan
Published: December 2014

A seventeen-year-old boy with juvenile diabetes mellitus developed fatal Candida meningitis with almost uncontrollable convulsions, following successful treatment of acute adrenal insufficiency. Autopsy demonstrated Candida abscesses of brain, kidney and heart, adrenal atrophy with lymphocytic infiltration, lymphocytic infiltration of pancreas, chronic thyroiditis and generalized lymphoid hyperplasia. Although positive Candida cultures are difficult to interpret in a diabetic, culture of the urine is essential for diagnosis of renal candidiasis. Blood-borne infections with C. albicans appear to involve the urinary tract even when meningoen-cephalitis or other organ involvement has not yet occurred. In retrospect this diabetic young man was clearly predisposed to candidiasis, and tooth extractions, steroid replacement for Addison's disease and later use of broad-spectrum antibiotics all played a role.
Specificity of Serotonin Inhibition of Insulin Release from Golden Hamster Pancreas
Authors: Feldman Jerome M , Lebovitz Harold E
Published: December 2014

Five-hydroxytryptamine (serotonin) inhibited basal and stimulated insulin release from pieces of golden hamster pancreas. Five-hydroxyindole acetic acid was a less potent inhibitor of insulin release than was serotonin, while 5- hydroxytryptophan and tryptamine had no effect on this process. In contrast, L-tryptophan potentiated high glucosemediated insulin release. Thus there was an absolute structural requirement for a hydroxyl group in the five position of the indole ring, and a relative requirement for an amine group in the alkyl chain for these indole compounds to be inhibitors of insulin release. In further studies, methysergide maleate, a specific serotonin inhibitor, blocked this action of serotonin. Methysergide maleate also stimulated glucose-mediated insulin release suggesting that endogenous serotonin may influence in vitro insulin secretion. Thus the inhibitory effect of serotonin on insulin secretion appears to be quite specific.
Influence of Fasting on Changes in Glucose Metabolism Induced by Growth Hormone Injection in the Normal Dog
Authors: Rathgeb Isabel , Steele Robert , Winkler Bertram , Altszuler Norman
Published: December 2014

Normal dogs were fasted four to eight days, then subjected to a regimen of bovine growth hormone (1 mg./kg. per day, intramuscularly) for an additional four to six days with fasting continued. Plasma glucose concentration, and the rate of release and uptake of circulating glucose (as measured with C-14-glucose), were not increased significantly by growth hormone. This contrasts with the increases seen in the normally-fed dog given growth hormone. Nevertheless, the growth hormone regimen produced very high plasma insulin levels (as measured by radioimmunoassay) in the long-fasted animals, and produced the usual resistance in these animals to the effects of administered insulin to enhance glucose uptake and diminish glucose release. Thus neither increased glucose turnover nor increased plasma glucose concentration is a required factor in the development of hyperinsulinemia and insulin resistance in the growth hormone-treated intact dog.
Juvenile Diabetes Mellitus in Immigrant Populations in Israel
Authors: Cohen T , Nelken L , Wolfsohn H
Published: December 2014

A study of the prevalence of juvenile diabetes mellitus was performed and 105 juvenile diabetics were detected among Israeli Jews in 1963. A check against hospital records indicated that the ascertainment was close to complete.

The prevalence of juvenile diabetes mellitus was estimated at about 1:6,000 at ages two to sixteen years. Among offspring of fathers born in Europe, America or Israel the prevalence was higher (0.24 per thousand) than among offspring of fathers born in Asia and Africa (0.09 per thousand).

The incidence among young children appears to be higher in recent years than in previous years.

Among 210 parents, five were reported to be diabetic, a frequency no greater than that of the general population. No diabetic sibling was reported in 1963 among 201 living siblings aged two to thirty-three years.
Reduction in the Activity of the Pancreatic Islets Induced in Normal Rodents by Prolonged Treatment with Derivatives of Sulfonylurea
Authors: Sodoyez Jean-Claude , Sodoyez-Goffaux Francoise , Dunbar Joseph C , Foa Piero P
Published: December 2014

Normal Syrian hamsters were given daily intraperitoneal injections of tolbutamide sodium or 0.9 per cent NaCl solution. Normal albino rats were fed a control or a glyburide (HB-419) containing diet. After seven weeks of treatment, the animals were killed, the pancreatic islets were isolated by collagenase digestion and their diameter and secretory activity in vitro were measured. In other animals, the total pancreatic acid-alcohol extractable insulin was measured. In control animals, there was a linear relationship · between body weight on the one hand and pancreatic insulin content on the other. In animals previously treated with tolbutamide, at the dose of 63 mg./kg., the relationships between these two variables were altered: a slight increase in body weight was accompanied by a decrease in pancreatic insulin content. The islets of animals treated with either drug released less insulin in vitro than those of control animals; the degree of B cell depression was related to the dose of tolbutamide which the animals had received. All drug-induced abnormalities disappeared approximately one week after the cessation of treatment. The possible significance of these observations to human therapy is discussed.
Molecular Size of Extractable Glucagon and Glucagon-like Immunoreactivity (GLI) in Plasma
Authors: Valverde Isabel , Rigopoulou Demetra , Marco Jose , Faloona Gerald R , Linger Roger H
Published: December 2014

In order to determine the approximate molecular size of the plasma glucagon immunoreactivity originating in the pancreas and glucagon-like immunoreactivity (GLI) derived from the gastrointestinal tract, extracts of plasma, obtained from dogs under various conditions, were subjected to P-10 Bio-Gel filtration and the elution volume of the peaks of immunoreactivity was compared with that of insulin-I-131 and glucagon-I-131 markers.

In an assay system which measures both gastrointestinal GLI and pancreatic glucagon, an extract of fasting plasma was found to have two peaks of immunoreactivity, one peak in the glucagon-I-131 zone, the other in the preinsulin- I-131 zone. These peaks could not be discerned in an assay system specific for pancreatic glucagon and must, therefore, be of gastrointestinal origin. Plasma obtained from the mesenteric vein of a partially depancreatized dog following an intraduodenal glucose load contained the same two peaks which again reacted poorly in the glucagonspecific assay system, indicating gastrointestinal origin.

Pancreaticoduodenal vein plasma obtained from a dog during amino acid infusion revealed a very large peak of immunoreactivity in the glucagon-I-131 zone and a very small peak in the preinsulin-I-131 zone. Both peaks were readily measured in the glucagon-specific assay system, indicating their pancreatic origin. The eluates of the glucagon-I-131-sized peak had glucagon-like glycogenolytic activity in the perfused rat liver system and appeared to be identical to pancreatic glucagon.

It is concluded that the pancreatic glucagon and gastrointestinal glucagon-like immunoreactivity extractable from plasma have the same molecular size in their tissues of origin.
Effects of Insulin from Normal and Diabetic Human Pancreas on RNA Labeling in Fibroblast Cultures
Authors: Roy Claude C , Gotlin Ronald , Shapcott Dennis , Montgomery April , O'Brien Donough
Published: December 2014

The nutrient medium of a series of cultures inoculated simultaneously with mouse fibroblasts of the 3T6 strain was replaced by fresh medium containing Uridine-2-C-14 and 5,000 μunits of insulin from four normal and two diabetic pancreases. After a twelve-hour incubation period the cellular monolayer was subdivided by conventional chemical methods and the specific activity of the RNA fraction estimated. A consistent difference was observed between RNA specific activity of the cellular monolayers treated with diabetic pancreatic insulin and normal pancreatic insulin. These data constitute a further argument strengthening the case for an “abnormal insulin in diabetes mellitus.”
Effect of Experimental Diabetes Mellitus on Protein Synthesis by Liver Ribosomes
Authors: Tragl Karl H , Reaven Gerald M
Published: December 2014

Rats were made diabetic by the administration of either alloxan or anti-insulin serum (AIS), and the capacity of hepatic polysome preparations from these animals to incorporate aniino acid into protein in an in vitro incubating system was compared to that of similar preparations from normal animals. Hepatic polysomes from rats with either form of experimental diabetes were characterized by a marked reduction in their ability to carry out in vitro protein synthesis. Prior washing with 0.5 M NH4CI accentuated the abtivity difference between normal and diabetic ribosomes, suggesting that the decrease in amino acid incorporation of diabetic ribosomes was not related to loss of “initiation” factors. In contrast, normal monosomes (polysomes stripped of natural messenger RNA) were no more active than monosomes from diabetic animals when protein synthesis was directed by polyuridylic acid, and this relationship was independent of the concentration of either polyuridylic acid or MgCI2 in the incubation medium. These results are consistent with the thesis that the decrease in hepatic ribosomal protein synthesis that results from experimental diabetes mellitus is related to a concomitant decrease in the amount or availability of messenger RNA.
Decreased Response to Insulin in Adipose Tissue during Starvation: Effect of Hypophysectomy and Growth Hormone Administration
Authors: Trueheart P A , Herrera M G
Published: December 2014

Fasting for twenty-four hours or longer reduced basal glucose oxidation and incorporation into lipid in rat adipose tissue. The “in vitro” effect of 50 and 100 μU./ml. insulin was also found to be significantly decreased. A ten-fold increase in insulin concentration increased glucose metabolism to levels comparable to those observed in tissues from fed rats. Hypophysectomy diminished markedly the difference in response to insulin between fed and fasted rats. Injection of 50 μgm. of growth hormone every twelve hours restored this difference. It is concluded that adipose tissue responsiveness to insulin is markedly reduced by fasting and that the hypophysis is implicated in this phenomenon. Growth hormone appears to be one of the factors that mediates this change in insulin response.
Hypertriglyceridemia in Weanling Rats with Hypothalamic Obesity
Authors: Schnatz J David , Bernardis Lee L , Frohman Lawrence A , Goldman Jack K
Published: December 2014

Weanling rats with electrolytic destruction of the ventromedial hypothalamic nuclei (VMN) develop elevated plasma triglyceride and insulin levels despite normal food intake. Triglyceride, insulin and adipose tissue lipoprotein lipase activity (LPL) were studied in VMN and sham-operated (control) rats fed 0, 6 or 25 per cent fat diets. On a 25 per cent fat diet, plasma from VMN rats exhibited the highest triglyceride levels, immobile lipoproteins with trailing from the pre-beta region to the origin on electrophoresis, and visible top particles in polyvinylpyrrolidone columns. On 6 per cent fat, triglyceride levels were lower than on the 25 per cent fat diet but remained greater than those of the controls; immobile lipoproteins and visible top particles were absent but trailing of lipoproteins from the pre-beta region to the origin was still evident on an electrophoretic strip. On a fat-free diet, VMN and control plasma triglycerides were identical but subsequent fasting for forty-eight hours produced elevated triglycerides in VMN rats. The diet-dependent alterations in triglycerides, lipoprotein electrophoretic patterns and polyvinylpyrrolidone columns indicated a combination of endogenous and exogenous hypertriglyceridemia.

LPL was increased in VMN rats on all diets but was decreased to levels similar to those of control animals by forty-eight hours of fasting. The exogenous increase in triglycerides which occurred despite the increased adipose tissue LPL was investigated. These studies failed to demonstrate the presence of LPL inhibitors, decreased release of LPL into the circulation or resistance of lipoproteins to hydrolysis but suggested an impaired ability of VMN tissue to take up circulating lipid.
Effect of Local Anesthetics on Insulin Secretion by Pancreas Pieces
Authors: Bressler R , Brendel K
Published: December 2014

Because in vitro secretion is calcium dependent, a study was carried out to ascertain the effect of local anesthetics (LA) on glucose-induced insulin secretion by pancreas pieces.

Different classes of LA affected insulin secretion differently. Nonantiacetylcholine type LA with uncharged amino groups (holocaine, propranolol) depressed glucose-induced insulin secretion progressively as their concentrations were raised (10−3 to 1 mM). The inhibition was more marked at lower compared to higher calcium concentrations.

The antiacetylcholine type LA (mepivicaine, lidocaine) with charged tertiary amino groups had complex effects on insulin secretion. At low concentrations (10−4 mM) they acted as anticholinergic agents in their inhibitions of Mecholyl-stimulated insulin secretion. Complete blockade of Mecholyl-stimulated secretion was found at calcium concentrations of 0.5 and 3.0 mM. This concentration of LA did not, however, depress glucose-induced insulin secretion. At an LA concentration of 10−3 mM inhibition of glucosestimulated insulin secretion occurred, which was not reversed by higher concentrations of calcium. At still higher LA concentrations (0.05 to 1.0 mM) the inhibitory effect on glucose-induced insulin secretion diminished, disappeared and became a stimulatory effect, which was abolished by the addition of atropine.
Nephropathy in Sucrose-fed Rats: Electron and Light Microscopic Studies
Authors: Rosenmann E , Teitelbaum A , Cohen A M
Published: December 2014

Diffuse intercapillary glomerulosclerosis and exudative glomerulosclerosis were produced in rats fed high-sucrose diet for periods of nine to eighteen months. These lesions were observed by light and electron miscroscopy. Impairment of glucose tolerance was observed in the sucrose-fed animals and marked proteinuria developed in the course of long-term sucrose feeding. Such lesions did not develop in a control group of age-matched fed high-starch diets.
Diabetes Detection with a Comparison of Screening Methods
Authors: Orzeck Eric A , Mooney Joseph H , Owen John A
Published: December 2014

During a Diabetes Detection Drive, 559 persons were tested for hyperglycemia (Auto Analyzer and Dextrostix methods) or glycosuria (Clinistix and Dreypak methods) ninety minutes after a glucose load. Of 164 screened positive, 154 returned for standard glucose tolerance testing. Using the criteria of Fajans and Conn, forty-two new cases of diabetes were diagnosed; by age-adjusted criteria there were twenty new cases. Approximately one-third of these would have been missed by reliance on screening by glycosuria alone. Comparison of screening methods reveals the Auto Analyzer measurement of blood sugar to be more sensitive and therefore better for the intensive study of limited populations; however, the Dextrostix method is cheaper and quicker and may have some advantages in the usual mass detection efforts.
Metabolic Effects of Weight Loss in Obese Subjects: Changes in Plasma Substrate Levels, Insulin and Growth Hormone Responses
Authors: Kalkhoff R K , Kim H J , Cerletty J , Ferrou C A
Published: December 2014

Oral glucose tolerance and intravenous tolbutamide, glucagon and insulin tolerance were assessed in six obese patients before and after an average weight loss of eighty-five pounds and a reduction from 83 to 27 per cent above ideal body weight. Results were compared to ten nonobese subjects of similar age.

Before treatment fasting plasma glucose, free fatty acids and immunoreactive insulin exceeded normal levels. Total plasma alpha-amino acid nitrogen levels were unaffected by obesity. Post-challenge insulin responses during the first three tolerance tests were two to four-fold above control responses, and increments of immunoreactive growth hormone during insulin tolerance were subnormal in the obese. After weight reduction only minor differences in mean yjilues existed between obese and control groups.

These findings indicate that disturbances in fasting plasma substrate levels as well as plasma insulin and growth hormone responses fii obese individuals are reversible after substantial weight reduction.
Comparison of Antibody Responses in Normal and Alloxan Diabetic Mice
Authors: Dolkart Ralph E , Halpern Bernard , Perlman Janice
Published: December 2014

The reason for the increased incidence and severity of infections in diabetic patients has never been satisfactorily explained. This investigation was designed to study the circulating antibody response in alloxan diabetic, insulin treated diabetic and normal CF-1 mice injected with bovine serum albumin. Only those animals treated with alloxan who had elevated serum glucose levels (250 mg./100 ml. or higher) were included in the study, together with a group of normal animals. Animals were bled from the orbital sinus and the serum analyzed for antigen binding capacity of BSA, glucose concentration and serum proteins. BSA was iodinated with I-131 and the antigen binding capacity of each serum sample was determined as micrograms of BSA nitrogen bound by 1 ml. of undiluted serum. Our studies demonstrate that there is no significant difference in antibody response of alloxan treated mice, alloxan treated mice given insulin and normal mice when immunized with BSA under the conditions of the experiments. If the alloxan treated mouse may be considered a laboratory model of diabetes mellitus in man, the results described herein would be consistent with those studies of diabetics which have shown no primary defect in their immune systems.
Diphenylhydantoin-induced Hyperglycemia and Impaired Insulin Release: Effect of Dosage
Authors: Fariss Brace L , Lutcher Charles L
Published: December 2014

Elevated postprandial blood sugar levels were found in a forty-two-year-old Negro woman taking 400 mg. of diphenylhydantoin a day. After discontinuance of diphenylhydantoin, blood glucose levels and insulin responses were normal when oral and intravenous glucose tolerance tests and an intravenous tolbutamide test were performed. After taking 400 mg. diphenylhydantoin daily for two weeks the patient had decreased oral and intravenous glucose tolerance and an abnormal intravenous tolbutamide test with marked reduction in insulin response in all three tests. Oral glucose tolerance tests were within the limits of normal while the patient was receiving 300, 200, and 100 mg. diphenylhydantoin by mouth; however, the insulin response was decreased when the patient received 300 and 200 mg. diphenylhydantoin.
Rats Enriched with Odd-carbon Fatty Acids: Effect of Prolonged Starvation on Liver Glycogen and Serum Lipids, Glucose and Insulin
Authors: Xavier Pi-Sunyer F
Published: December 2014

Male rats were fed a complete diet containing 30 per cent of calories as fat, with corn oil exclusively in the controls and a 7:3 mixture of triundecanoin (C11) and corn oil in the experimental group. After six weeks, rats were sacrificed in the fed state and at 24, 48, 96 and 144 hours of starvation. In the experimental group, adipose tissue fatty acids were enriched with undecanoate to an average of 28 per cent of total fatty acids. Serum glucose was found to be significantly higher in the experimental group at all periods of starvation, and liver glycogen in the experimental rats was significantly higher at 48, 96 and 144 hours of starvation. Planimetry of the area circumscribed by values plotted from 24 to 144 hours of starvation gave mean values of immunoreactive insulin of 22.37 mU. hours per ml. for the experimental versus 13.55 mU. hours per ml. for the control group (P < .005), and mean values of free fatty acids of 967 mEq. hours/L. for the experimental versus 1,128 mEq. hours/L. for the control group (P < .05). Weight loss and nitrogen excretion were not significantly different among the two groups, nor were levels of serum cholesterol and triglycerides.

The data suggest that during prolonged starvation, the odd chain, fatty acid-enriched animals are capable of maintaining liver glycogen and serum glucose better than even-chain-enriched control animals. These changes are reflected in concurrently higher serum immunoreactive insulin and lower free fatty acid levels. The odd-chain fatty-acid-enriched rat appears to be endowed with potentially glucogenic fatty acids.
Portal Vein Insulin Concentrations in Diabetic Subjects
Authors: Blackard William G , Nelson Norman C
Published: December 2014

Portal vein immunoreactive insulin (IRI) concentrations following intravenous glucose were compared in diabetics and nondiabetics. Diminished pancreatic insulin secretion rather than extrapancreatic factors explains the peripheral insulinopenia observed in diabetics. Early insulin release (acute pool) was impaired more than delayed release (chronic pool) in the diabetics.
Acid Phosphatase Activity in Secretory Granules of Pancreatic Beta Cells of Normal Rats
Authors: Orci Lelio , Stauffacher Werner , Rufener Claude , Lambert André E , Rouiller Charles , Renold Albert E
Published: December 2014

A cytochemical staining method for acid phosphatase combined with electron microscopy was applied to the islets of Langerhans of adult normal rats. In addition to dense bodies, some Golgi cisternae as well as a varying number of secretory granules of β cells were found to contain acid phosphatase. In view of the paucity of the knowledge concerning the role of acid phosphatase, the possible functional significance of its presence in the secretory granules of pancreatic β cells cannot be denned at the present time.
Application of the Intravenous and Oral Glucose Tolerance Tests in Pregnancy
Authors: Silverstone F A , Posner N A , Pomerance W , Cramer M , Breuer Joseph
Published: December 2014

Using recently available pregnancy criteria a direct comparison of both the intravenous GTT and the oral GTTs was undertaken in 149 pregnant women. In suspects, intravenous testing gave a higher yield (16 per cent) than oral testing (8 per cent). Nonpregnantoral criteria gave the lowest yield in suspects (7 per cent) and a number of nondiagnostic responses (30 per cent) which did not parallel the degree of clinical risk and appearednormal by other nonpregnant criteria.

The advantage of a one-hour test expressed in a convenient numerical index of tolerance, combined with favorable sensitivity in suspects should favor the use of the intravenous glucose tolerance test in pregnancy.
Insulin Across Respiratory Mucosae by Aerosol Delivery
Authors: Wigley Frederick M , Londono Javier H , Wood Scott H , Shipp Joseph C , Waldman Robert H
Published: December 2014

Insulin, a protein of about 5,700 molecular weight, was delivered by aerosol inhalation to three normal volunteers and to four patients with diabetes mellitus. Direct evidence of absorption of insulin across mucosae of the respiratory tract was an increase in plasma IRI. Biologic activity of insulin absorbed by inhalation was shown by hypoglycemia temporally correlated with the increase in plasma IRI. No untoward reactions were observed.
Biphasic Insulin Release from Perifused Cultured Fetal Rat Pancreas: Effects of Glucose, Pyruvate, and Theophylline
Authors: Burr Ian M , Kanazawa Yasunori , Marliss Errol B , Lambert André E
Published: December 2014

Recent interest in the dynamics of insulin release in the adult has prompted the investigation of immunoreactive insulin (IRI) release profiles during perifusion of cultured fetal rat pancreas, a preparation previously studied extensively in a static incubation system. Glucose alone (16.4 mM) induced an early (primary) IRI release response and a minimal later (secondary) response. Pyruvate alone (16.4 mM) evoked no response above baseline. Addition of 2.5 mM theophylline to either of these substrates resulted in enhanced and biphasic IRI release, the theophylline effect occurring predominantly in the second phase. With glucose as substrate, increasing the theophylline concentration to 10 mM caused similar enhancement of the primary response, but less enhancement of the secondary response, by comparison with 2.5 mM theophylline. By contrast, 10 mM theophylline further enhanced the secondary response to pyruvate. Hence, this preparation of cultured fetal rat pancreas resembled adult rat pancreas with respect to the first phase of IRI release in response to glucose. However, the much smaller secondary response to glucose alone contrasted markedly with that of the adult, and appears to explain the relatively poor responsiveness to glucose of fetal and newborn rat pancreas during incubation.
Energy Metabolism in Pancreatic Islets of Rats: Studies with Tolbutamide and Hypoxia
Authors: Krzanowski J J , Fertel R , Matschinsky F M
Published: December 2014

Levels of ATP, phosphocreatine, glycogen and glucose of individual pancreatic islets were measured by quantitative histochemical technics. The islets were obtained from frozen-dried sections and were analyzed with enzymatic fluorometric methods coupled to enzymatic cycling and using an oil well technic. The rate of energy consumption in the islets was estimated by the rate of change in energy stores under complete ischemia. The energy use rate of the pancreatic islet was 38 mmoles of ∼ P per kg. dry tissue per min. which is approximately 50 per cent of the rate in brain. Tolbutamide (5 mg./kg. or more in vivo) resulted in a peak of insulin release one minute after administration. Regardless of the dose employed, ATP and phosphocreatine were unchanged one minute after tolbutamide, when insulin output was maximal or thirty minutes after the drug, when serum insulin levels were falling. In addition, ATP and P-creatine levels were unchanged in islets from the perfused pancreas thirty seconds after eliciting at least a sixfold increase in insulin secretion by perfusing with media containing 50 jug./ml. tolbutamide, whether glucose was present or absent in the medium. Since the readily available energy reserves were not affected by exposure to tolbutamide, the metabolic rate of the islets was either not influenced by the drug or the effect was small or well compensated.
Diabetic Glomerulosclerosis in Children
Authors: Balodimos Marios C , Legg Merle A , Bradley Robert F
Published: December 2014

A boy died in diabetic acidosis at the age of nine, after seven years of known diabetes. At necropsy there was diffuse glomerulosclerosis by light microscopy, evidenced by diffuse mesangial thickening of the peripheral glomeru-lar loops and irregular thickening of the capillary basement membrane of the glomeruli. Glomerulosclerosis is a rare finding in a person of this age as revealed in a review of the literature.
Laboratory Assessment of Diabetic Pregnancy: A Brief Review
Authors: Kahn Charles B , White Priscilla , Younger Donna
Published: December 2014

Pregnancy in the diabetic is at high risk. Recent efforts to improve perinatal mortality have principally been directed at establishing a laboratory assessment which could be used in the management of the diabetic pregnancy. Data on the hormones—estrogen, progesterone, human placental lactogen (HPL) and human chorionic gonadotropin (HCG) and on the enzymes—heat-stable alkaline phosphatase (HSAP) and diamine oxidase (DAO) are briefly reviewed for uncomplicated and for diabetic pregnancies.
Circulating C-peptide Immunoreactivity: Studies in Normals and Diabetic Patients
Authors: Block Marshall B , Mako Mary E , Steiner Donald F , Rubenstein Arthur H
Published: December 2014

The discovery of proinsulin and recognition of its intracellular conversion to insulin and C-peptide, which are stored and subsequently secreted together, have provided a simple method for monitoring β-cell function in insulinrequiring diabetics in whom insulin antibodies hinder measurement of immunoreactive insulin. Using an antiserum which reacts with antigenic determinants in human Cpeptide and this region in proinsulin and its intermediates we have measured C-peptide immunoreactivity (CPR) in unextracted serum and characterized its components.

During oral glucose tolerance tests (OGTT) in nine healthy subjects, fasting serum CPR was 1.3 ± 0.3 ng./ml. and peaked at 4.4 ± 0.8 ng./ml. (60 min.). These values were positively correlated with immunoreactive insulin levels (IRI). CPR was undetectable in five newly diagnosd, untreated diabetics with fasting blood sugars above 200 mg./100 ml. and unmeasurable IRI. Similarly, serum CPR could not be measured in five ketosis-prone juvenile diabetics who had received insulin for longer than five years.' In contrast, fasting CPR was 2.7 ± 0.7 ng./ml. in twelve insulin-treated adult onset diabetics and rose to 5.0 ± 1.1 ng./ml. two hours after glucose. Several of these sera were extracted in acid-ethanol, gel-filtered. and measured against human proinsulin and C-peptide standards. Fasting proinsulin levels were markedly elevated, while C-peptide levels were comparatively low. Both components increased after glucose administration. As these diabetics had circulating insulin antibodies it was postulated that the elevated proinsulin levels represented circulating proinsulininsulin antibody complexes. Evidence favoring this possibility was derived from in vitro experiments in which human I-125-proinsulin was incubated with diabetic sera and the samples analyzed by gel filtration, paper electrophoresis and immune precipitation. Similar experiments with 1-125-C-peptide showed no evidence for preferential binding to plasma proteins in diabetic sera.

Residual β-cell secretory capacity is thus present in many insulin-treated adult onset diabetics. The C-peptide immunoassay should facilitate the prospective study of β-cell function in these patients.
Metabolic Studies Following the Oral Ingestion of Different Doses of Glucose
Authors: Förster Harald , Haslbeck Manfred , Mehnert Hellmut
Published: December 2014

Oral glucose tolerance tests were performed with variable glucose loads (30 gm., 50 gm., 100 gm., 200 gm., 300 gm.) in groups of healthy subjects. The concentrations of blood glucose, serum insulin and free fatty acids were measured in venous blood. Blood glucose concentration was also determined in capillary and arterial blood. The differences in glucose concentrations between capillary and venous blood were as high as 40 mg./lOO ml. The magnitude of the differences was related both to the time of determination and to the glucose load. One hundred and twenty minutes after beginning the tests there were little differences between the glucose concentration in capillary blood and in venous blood after doses of 30 or 50 gm. glucose. With larger doses of glucose higher values than the pretest values were still found in capillary blood but not in venous blood at the same time and also 180 min. after beginning the tests. Also, in contrast to the findings with doses of 30 or 50 gm. glucose, serum insulin levels were still elevated at 120 minutes after the higher glucose loads. The high values of serum insulin (70 to 90 μU./ml.) and the concentration differences between capillary and venous blood are explained best by the secretion of biologically active insulin because of a continual intestinal absorption of glucose. This confirms the assumption that the secretion of insulin is obviously not only stimulated by the actual blood glucose concentration but also by intestinal absorption of glucose. This mechanism is important in the oral glucose tolerance test because only 120 minutes after a load of 100 gm. glucose there is a continuous insulin secretion.
Comparison of the Effects of Metabolic Acidosis and Acute Uremia on Carbohydrate Tolerance
Authors: Weisinger José , Swenson Robert S , Greene Warner , Taylor J Bradley , Reaven Gerald M
Published: December 2014

In an attempt to assess the role of metabolic acidosis in the glucose intolerance of uremia, we have estimated insulinmediated glucose uptake in normal dogs, in acidotic dogs with normal renal function, and in uremic dogs. Mean steady state plasma glucose and insulin levels were measured in eighteen dogs (pH 7.4 ± .01) during constant infusion of glucose and insulin, while endogenous insulin secretion was suppressed by infusion of propranolol and epinephrine. The dogs were then divided into three groups: moderate acidosis was produced by giving 7 gm. NH4Cl/ day for four days; severe acidosis, 12 gm. NH4Cl/day for four days; and uremia (serum creatinine 15.7 ± 0.2 mg. per cent) by anastomosing both ureters to the vena cava. Duplicate infusions were then performed and the results compared to control values. Plasma insulin levels were identical, despite the presence of either acidosis or uremia. The mean increase in plasma glucose in moderate acidosis (pH 7.2 ± 0.1) over controls was 39 mg./l00 ml. (p < .05); in severe acidosis (pH 7.0 ± .04) plasma glucose increased by 69 mg,/100 ml. (p < .01). However, the mean increase in plasma glucose (149 mg./100 ml.) in uremia (pH 7.3 ± .03) was significantly greater (p < .005) than that following acidosis, although the pH did not significantly fall. Thus, although metabolic acidosis results in deterioration of glucose tolerance, the magnitude of the change does not seem able to account for the carbohydrate intolerance of uremia.
Effect of Sodium Linoleate Infusion on Plasma Free Fatty Acids, Glucose, Insulin, and Ketones in Unanesthetized Dogs
Authors: Crespin Stephen R , Greenough William B , Steinberg Daniel
Published: December 2014

By using a continuous-flow centrifuge to separate carotid artery blood into cells and plasma, sodium linoleate was infused into the jugular vein of five conscious dogs at a mean rate of 41.9 μEq. · kg.−1 · min−1 for ninety minutes without adverse side effects. Linoleate infusion quickly elevated plasma free fatty acid (FFA) levels to approximately 1.50 μEq./ml. and was accompanied by a rapid four- to sixfold increase in plasma immunoreactive insulin (IRI) which was sustained throughout the infusion. After thirty minutes of infusion, plasma glucose began to fall, ultimately declining 35 per cent from control levels. Plasma ketone levels rose to twice their control levels during linoleate infusion but were always less than 20 per cent of the ketone levels shown to be insulinogenic in dogs. Upon termination of the infusion, plasma FFA, IRI, and ketones fell quickly to control levels, while plasma glucose rose toward normal.

The half-life of plasma linoleate, estimated from the infusion rate and the increment in plasma FFA during steady-state infusion, was 0.76 minute. This result, based on net flux, validates estimates based on tracer experiments.

The similarity between the metabolic responses to linoleate infusion and those previously found to oleate suggests that these effects may be common to most physiologic long-chain FFA. Stimulation of insulin secretion by high levels of FFA could thus play a role in modulating lipolytic responses and changes in glucose metabolism accompanying such responses.