bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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.
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.
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.
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.
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 &lt; .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 &lt; .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.
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.
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.
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.