bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling Blood Glucose and Insulin Kinetics in Normal, Diabetic and Obese Subjects
Authors: Segre G , Turco G L , Vercellone G 
Published: December 2014

A two-compartment model (figure 1) and digital computer technics have been applied to the analysis of glucose and insulin control mechanisms in twenty-six normal, sixteen diabetic, and eight obese subjects. The system was perturbed by infusing glucose (0.5 gm./min. for about 300 minutes) into the three groups or by injecting glucose intravenously as an impulse of 0.33 gm./kg.; plasma insulin and glucose levels were determined and the model was solved by simultaneously fitting to it the experimental data for glucose and insulin, and the additional information gathered by determining the blood disappearance curve of intravenously injected C-14-glucose.
A discriminant analysis for two groups gave a statistically significant separation between normal and diabetic subjects (with infused or impulsive glucose) and between normal and obese subjects (with infused glucose) on the grounds of the seven parameters that characterize the model.
The prominent feature of the diabetics (in addition to the obvious hyperglycemia) was a decrease of λ21 (figure 1), a parameter which measures the insulin response to a glucose load. The prominent feature of the obese subjects was an increase of λ21 and a decrease of —λ21, a parameter which measures the glucose response to insulin. These dynamic characteristics are in agreement with present knowledge of the impairment of glucose and insulin control mechanisms in these pathologic states.
Proinsulin-Specific Antibodies in Human Sera
Authors: Kumar Dinesh , Miller Leona V 
Published: December 2014

Sera from nine diabetic patients treated with commercial insulin contained antibodies which reacted to I-125-bovine proinsulin. These antibodies had two distinct components: anti-insulin antibodies which crossreacted with proinsulin, and antiproinsulin antibodies, which were specific to proinsulin and did not react with insulin (purified, single component). Proinsulin-specific antibodies were detectable by their binding to I-125-bovine proinsulin in sera adsorbed with insulin-phe-sepharose or in sera preincubated with excess insulin.
I-125-bovine pro insulin-reactive antibodies showed species specificity. They reacted weakly with porcine proinsulin and appeared to have no crossreactivity with porcine-C-peptide.
The data suggest that proinsulin-specific antibodies (a) may be induced by the contaminants present in commercial insulin; (b) do not inactivate exogenous insulin and therefore, would not influence directly the daily insulin requirements of diabetic individuals.
Stimulation of H-3-Leucine Incorporation into the Proinsulin and Insulin Fraction of Isolated Pancreatic Mouse Islets in the Presence of Glucagon, Theophylline and Cyclic AMP
Authors: Schatz H , Maier V , Hinz M , Nierle C , Pfeiffer E F 
Published: December 2014

Incorporation of H-3-leucine into proinsulin and insulin and insulin secretion were determined in isolated pancreatic islets of mice. Batches of forty islets were incubated for three hours at 0, 100 or 300 mg. per cent glucose alone or in the presence of glucagon, theophylline or cyclic AMP. Proinsulin and insulin were separated by gel filtration on columns of Sephadex C50fine in 1 M. acetic acid.
In the absence of glucose, no stimulation of insulin biosynthesis as judged from the incorporation of H-3-leucine was observed with glucagon, cyclic AMP or dibutyryl cyclic AMP; insulin, secretion was not significantly stimulated. At 100 and 300 mg. per cent glucose, both leucine incorporation and insulin secretion were potentiated by the substances tested; the effect of glucagon was pronounced mainly at high concentrations of glucose. However, leucine incorporation and insulin secretion were not stimulated to the same extent in all cases.
Biosynthesis of insulin thus appears to be not always directly linked to insulin secretion. It is suggested that glucagon and the adenylcyclase system, besides regulating insulin secretion, are involved in insulin biosynthesis.
Absorption of Insulin from Perfused Rabbit Small Intestine in Vitro
Authors: Shichiri Motoaki , Etani Nobuaki , Kawamori Ryuzo , Karasaki Kenkichi , Okada Akira , Shigeta Yukio , Abe Hiroshi 
Published: December 2014

The intestinal absorption of insulin has been studied in a preparation of isolated rabbit intestine in which artificial plasma is circulated through normal vascular channels. After insulin in doses of 100, 200, and 440 U. was introduced into the intestinal lumen, its appearancein the venous effluent was measured immunologically during perfusion for two hours.
Insulin gradually appeared in the venous effluent and reached a peak fifty to ninety minutes after the perfusion was started. The proportion of insulin absorbed was 6.2 to 9.2 per cent with a dose of 100 U., 5.9 to 15.6 per cent with 200 U., and 8.9 to 15.9 per cent with 440 U. The amount of insulin added significantly correlated with the total amount of insulin absorbed from the intestine. The biologic activity in the fraction absorbed was equivalent to that obtained immunologically. In the venous effluent, insulin component was also identified by the relative mobility similar to crystalline insulin on acrylamide gel electrophoresis.
Although the intestinal absorption in this system does not duplicate physiologic absorption, these results indicate that a considerable portion of insulin can be absorbed from the intestine in a physiologically active form.
Glutamine and Glutamate Metabolism in Normal and Diabetic Subjects
Authors: Felig Philip , Wahren John , Karl Irene , Cerasi Erol , Luft Rolf , Kipnis David M 
Published: December 2014

Arteriovenous differences across the leg and across the splanchnic bed were determined for plasma glutamine and glutamate in healthy controls and insulin-dependent diabetics. In both groups glutamine was released from the leg and taken up by the splanchnic bed, while the reverse was observed for glutamate. Arterial glutamine levels were reduced by 25 per cent in the diabetics, but no differences were observed between the diabetics and controls in splanchnic or peripheral glutamine and glutamate metabolism. To assess the contribution of intestinal tissues to splanchnic glutamine uptake, arterio-portal venous differences (A-PV) were determined for plasma glutamine in four nondiabetic patients prior to elective cholecystectomy. A consistently positive A-PV difference was noted indicating net uptake of glutamine by intestinal tissues.
The findings indicate that the intestinal tract rather than the liver is the major site of splanchnic glutamine uptake and that removal of glutamine by the splanchnic bed is not augmented in diabetes. The data thus suggest that glutamine is not an important endogenous substrate for hepatic gluconeogenesis.
Carbohydrate Metabolism in Pregnancy: X. Metabolic Disposition of Alanine by the Perfused Liver of the Fasting Pregnant Rat
Authors: Metzger Boyd E , Agnoli Francis S , Hare John W , Freinkel Norbert 
Published: December 2014

Hepatocytes from pregnant rats fasted during late gestation are larger and more abundant than in littermate virgin animals and in vivo are exposed to hypoglycemia. To evaluate their intrinsic potential for biosynthetic transformations of alanine, a modified liver perfusion system was employed. Livers from twenty-four hour fasted, nineteenday pregnant and virgin littermate rats were subjected to “wash out” perfusion for twenty-five minutes prior to definitive perfusion for sixty minutes with fresh media containing supramaximal amounts of L-alanine-14-C (17 mM). Under such conditions, livers from pregnant rats displayed an enhanced capacity to assimilate alanine-14-C and to establish concentration gradients for alanine between hepatocytes and perfusion medium. Significantly more alanine carbons were incorporated into glucose, lactate, glyceride-glycerol, and glutamate per hepatocyte by livers of pregnant rats. Clyceride-glycerol formation was disproportionately enhanced suggesting that there may be mechanisms operative during pregnancy for selectively diverting triose phosphates toward the esterification of intrahepatic fatty acids. Despite the augmented disposition of alanine carbons, livers from pregnant animals formed significantly less urea. Instead, a much greater proportion of the nitrogen derived during alanine catabolism was released in a potentially reutilizable form, ammonia.
Thus, hepatocytes from fasted pregnant animals have an enhanced capacity for assimilating “loading” doses of alanine and for incorporating the carbons into glucose, lactate, glyceride-glycerol, and glutamate, while preserving more of the amino nitrogen in a form that can be reutilized.
Mode of Action of N6-O2′-Dibutyryl Cyclic 3′, 5′ AMP on Fat Cell Metabolism
Authors: Jarett Leonard , Smith Robert M 
Published: December 2014

Cyclic nucleotide phosphodiesterase (PDE) activity was measured by a 3H cAMP method on the infranatant portion of the homogenate of adipocytes isolated from rat epididymal fat pads. DBcAMP (0.05 to 1.0 mM.) was found to progressively inhibit the PDE activity. The inhibition was not secondary to dilution of the 3H cAMP by cAMP derived from catabolism of the DBcAMP by deacylase activity in the homogenate. Adipocytes were prelabeled with radiocarbon adenine and the hydrolysis of radiocarbon cAMP was measured in the presence and absence of DBcAMP. Increasing concentrations of DBcAMP prevented the hydrolysis of the radiocarbon cAMP in a dosedependent manner with no breakdown occurring at 1.0 mM., correlating with the complete inhibition of the homogenate PDE activity at 1.0 mM. Kinetic analysis revealed the low Km of the PDE to be 0.8 μM., and this was shifted to 2.5 μM. by 0.05 mM. DBcAMP without a change in Vmax, indicating a competitive-type inhibition which was easily reversible upon removal of the DBcAMP.
The cAMP levels were measured in extracts of DBcAMP-treated adipocytes by the protein kinase technic. DBcAMP and O2′ MBcAMP did not affect the assay system until 200 pmoles were present, while N6 MBcAMP was indistinguishable from cAMP in the assay system set for a standard curve of 0.5 to 10 pmoles. A procedure was devised to separate the cAMP from DBcAMP and O2′ MBcAMP such that they would always be at levels too low to interfere with the assay. N6 MBcAMP was shown not to be present in the assayed material since the material was susceptible to PDE digestion and N6 MBcAMP was not. Cellular cAMP levels increased as DBcAMP increased, reaching over fifty times the control at 1.0 mM. DBcAMP. This cAMP was shown to be over 90 per cent of endogenous origin and less than 10 per cent from breakdown of DBcAMP. Lipolysis was stimulated proportional to the increase in cAMP levels but was not maximal until the fiftyfold elevation of cAMP. This suggested that DBcAMP might compete with cAMP in activating the enzymes involved in lipolysis and that the large excess of cAMP is required to overcome this antagonism by DBcAMP.
A Clinical and Histologic Study of Diabetic Nephropathy in the Pima Indians
Authors: Kamenetzky Stephen A , Bennett Peter H , Dippe Stephen E , Miller Max , LeCompte Philip M 
Published: December 2014

The relationship of renal disease to carbohydrate tolerance was examined in the Pima, who are American Indians with a high prevalence of diabetes mellitus. Glucose tolerance, serum creatinine level and urine protein concentration were measured in 1,716 subjects aged fifteen and over, of whom 404 were diabetic. Histologic information was obtained by reviewing autopsy material from forty-three diabetics and sixty-two nondiabetics.
Over 22 per cent of the diabetics and less than 7 per cent of the nondiabetics had proteinuria (p &lt; 0.001). Severe proteinuria aid elevated serum creatinine levels were, respectively, fifteen and nine times more common in the diabetics (p &lt; 0.001). Both the frequency and severity of renal disease increased with duration of diabetes in subjects who were under age sixty-five when examined or when the disease was diagnosed. Above age sixty-five the prevalence of proteinuria was high in all duration groups.
At autopsy, 65 per cent of the diabetics had diffuse glomerulosclerosis. Nodular glomerulosclerosis was found in 56 per cent of the diabetics and in none of the nondiabetics. Arteriolar lesions were also significantly more common in the diabetics. Pyelonephritis was found in 16 per cent of the diabetics and 5 per cent of the nondiabetics; other forms of renal disease were rare in both groups.
Diabetic nephropathy, similar in its clinical and histologic characteristics to that described in other populations, is the predominant form of kidney disease in the Pima Indians, making this population ideal for study of the development and course of diabetic renal disease.
Impaired Leukocyte Function in Patients with Poorly Controlled Diabetes
Authors: Bagdade John D , Root Richard K , Bulger Roger J 
Published: December 2014

In order to assess the influence of poor diabetes control on function of leukocytes, polymorphonuclear leukocytes (PMN's) from patients with poorly controlled but nonketotic disease were studied before and after therapy. Before treatment, phagocytosis was significantly reduced (p &lt; .001) and, consequently, the rate of killing the test organism (type 25 pneumococcus) was decreased (p &lt; .01). Following antidiabetes therapy phagocytosis improved significantly; while microbicidal rates also improved, they remained less than control values (p &lt; .01).
Serum from the untreated diabetics uniformly reduced phagocytosis and microbicidal rates of control granulocytes; serum from controls improved phagocytosis by the diabetic PMN's, but restored normal microbicidal rates in only half of the patients. This transferable inhibitory effect of hyperglycemic diabetic serum on control granulocytes was abolished by dilution, and was reproduced in normal serum by the isosmotic addition of glucose. These studies suggest that (1) PMN function may be impaired during periods of poor diabetes control, as has been shown previously in ketoacidosis, and (2) hyperglycemia or a closely related factor may contribute to the defect.
Arginine Infusion in Dogs: Model for the Roles of Insulin and Glucagon in Regulating Glucose Turnover and Free Fatty Acid Levels
Authors: Cherrington A D , Kawamori R , Pek S , Vranic M 
Published: December 2014

Arginine administered to normal dogs indicated that glucose production (Ra) and glucose utilization (Rd) increased concomit-antly and plasma free fatty acid (FFA) levels decreased. The present studies were designed to assess the role of the simultaneously released pancreatic hormones in mediation of these responses. The amino add was administered to seven depancreatized insulin-infused dogs during periods when the normal pancreatic hormone response could not occur, and compared with periods during which insulin and glucagon were administered exogenously in patterns resembling the normal endogenous responses.
The amino add had no effect on glucose turnover in the absence of pancreatic hormone mobilization. However, normal increments in Ra and Rd occurred when extra insulin and glucagon were given concurrently with arginine; in order to maintain a sustained increment in Ra it was necessary to continually decrease the plasma insulin-glucagon (I/G) ratio. The metabolic effectiveness of a given I/G ratio thus varied with time. It appears that in assessing the metabolic significance of the I/G ratio, the duration of the stimulus and the absolute concentrations of the two pancreatic hormones should be considered. Despite pancreatectomy, basal concentrations of immunoreactive glucagon were within normal range prior to glucagon infusion; a nonpancreatic source of this activity is hypothesized. The plasma nonpancreatic glucagon immunoreactiv-ity increased only slightly in response to arginine. A comparable decrease in the FFA level occurred regardless of the presence or absence of extra insulin and glucagon, suggesting a nonpancreatic factor in the arginine associated inhibition of FFA release.
Thus arginine infusion acutely reverses the pattern of fuel utilization characteristic of fasting: glucagon increases glucose production by the liver, insulin increases overall glucose utilization and FFA levels fall. Arginine challenge cannot only reveal metabolic defidendes of insulin lack but also defidendes due to absence of pancreatic glucagon.
Sustained Insulin Release in Response to Intravenous Infusion of Insulin Releasing Polypeptide (IRP) in the Rat
Authors: Shabaan Ahmad A , Turner Desmond S , Marks Vincent 
Published: December 2014

A greatly elevated and sustained insulinemic response was evoked in cats by the intravenous infusion of a solution of IRP in glucose compared with that produced by glucose alone. Larger doses of IRP produced correspondingly greater increases in insulin release.
IRP enhanced glucose disposal up to a finite limit despite higher plasma insulin levels suggesting that there is a maximum rate of glucose disposal under conditions of intense insulin stimulation.
Effects of Diphenylhydantoin upon Glucose-induced Insulin Secretion in Three Patients with Insulinoma
Authors: Hofeldt Fred D , Dippe Stephen E , Levin Seymour R , Karam John H , Blum M Robert , Forsham Peter H 
Published: December 2014

Because diphenylhydantoin (DPH) has been shown to inhibit nontumorous insulin release, we evaluated its effects in patients with insulinoma.
Three patients with surgically demonstrated insulinomas were tested with oral and intravenous glucose before and after DPH. In two of these patients, we compared the effects of DPH and diazoxide.
Ingestion of DPH for several days did not alter fasting glucose or insulin. Poststimulatory insulin was appreciably reduced in only one patient during treatment with the drug. During diazoxide administration, this patient had increased fasting glucose and decreased fasting insulin, in addition to reduction of poststimulatory insulin. Combined DPH-diazoxide therapy in this patient did not produce greater effects than did diazoxide alone. Neither fasting ingulin or glucose nor poststimulatory insulin secretion were influencse by DPH or diazoxide in the second patient, or affected by DPH alone in the third.
The accepted role of DPH in the treatment of insulinoma involves its ability to alter seizure threshold. It did not influence fasting hypoglycemia in our patients. Reduced insulin secretion after stimuli might reflect effects of DPH on responses of nontumorous endocrine pancreas.
Insulin and Growth Hormone Secretion in Rats with Ventromedial Hypothalamic Lesions Maintained on Restricted Food Intake
Authors: Martin Julio M , Konijnendijk Willem , Bouman Paul R 
Published: December 2014

Adult female rats were trained for one week to consume a subnormal amount of food (12 gm.) in two one-hour feeding sessions per day: 4 gm. between 8 and 9 a.m. and 8 gm. between 6 and 7 p.m. At the end of the training period the animals were subjected to either bilateral electrolytic destruction of the ventromedial hypothalamus (VMH) or to a sham operation. The restricted feeding regime was continued for forty-eight hours postoperatively, when comparative studies were made. Plasma insulin response to intravenous Glibenclamide was greater in the rats with VMH lesions than in the pair-fed, sham-operated controls. The former rats also exhibited decreased initial plasma glucose levels, degranulation of the beta cells and reduced pancreatic insulin content. In addition to marked islet enlargement, similar though more severe signs of islet hyper-function were observed in rats with VMH lesions fed ad libitum, which became hyperphagic immediately after the operation.
VMH lesions did not significantly affect the plasma and pituitary levels of growth hormone (GH). The restricted feeding regime, however, caused an increase in plasma GH, responsiveness to hypoglycemic stimulation and a tendency to decreased pituitary GH content both in injured and sham-operated rats.
These findings indicate that VMH lesions per se enhance the responsiveness of the pancreatic islets to insulin secretory stimulation independent of changes in food intake, meal size and meal frequency. The resulting hyperinsulinism might play an essential role in the occurrence of hypothalamic hyperphagia and obesity following VMH injury. In hyperphagic rats with VMH damage, the islet stimulation is magnified, possibly due to the combination of a direct hypothalamic effect plus the secondary effect of increased food intake. Defective secretion of GH does not appear to be primarily involved in the induction of the hypothalamic syndrome.
Perifusion of Pancreas Fragments: A System for the Study of Dynamic Aspects of Insulin Secretion
Authors: Kikuchi Masatoshi , Rabinovitch Alexander , Blackard William G , Renold Albert E 
Published: December 2014

A perifusion system, intermediate in character between perfusion and static incubation, is described for the investigation of the multiphasic aspects of insuiin secretion from pancreas not subjected to separation of endocrine and exocrine tissue. Pancreatic tissue fragments obtained by mechanical chopping with razor blades are placed in small (0.7 ml.) chambers through which medium is pumped and from which effluent is collected at various time intervals for IRI determination. Under the conditions employed, insulin degradation by released proteolytic enzymes is minimal throughout the test period. Dose-dependent glucose-induced insulin release is observed and decreases immediately after cessation of the stimulus. Pancreas from fed animals secretes significantly greater quantities of insulin in response to glucose thata pancreas from fasted animals. Optimal results are obtained when the chopped tissue fragments average (0.5 mm.)3.
The secretion profiles obtained with this system are similar to those reported with pancreatic perfusion. Tolbutamide produced an early insulin response only, whereas glucose and amino acids induced both early and late insulin secretory responses. Among the hexoses tested, only glucose and mannose stimulated insulin secretion, whereas two inhibitors of the early steps of glucose metabolism, mannoheptulose and 2-deoxygIucose, inhibited both the early and late phases of glucose-induced insulin secretion.
The separation between the two phases of insulin secretion is not as sharp and complete with perifusion as with perfusion. This difference is presently attributed to the greater role of tissue diffusion in the minced perifused tissue. Balancing this disadvantage, however, perifusion offers several advantages over perfusion, among which are ease of tissue preparaton and handling, ability to study a number of variables relatively rapidly, comparison of identically prepared and randomly sampled minces of the same pancreas in parallel.
Finally, the preparation is applicable whenever pancreatic perfusion is not possible (for example, in the fetus or for very small animals), or when the isolation of islets of Langerhans presents practical or theoretical disadvantages, as in the study of the influences of exocrine on endocrine tissue.
Atherosclerotic Lesions in Diabetes
Authors: Bevans Margaret 
Published: December 2014

Since arteriosclerosis accounted for 69.4 per cent of deaths in a series of diabetic subjects in the five-year period from 1944 to 1949, it seems appropriate to reassess our knowledge of this serious complication of diabetes in the last trimester of 1954.
“Atherosclerotic lesions” I have interpreted as meaning those lesions, primarily intimal, which occur in the large and medium-size arteries of the body. Within the limitations of this paper the term “atherosclerosis” will be considered to be synonymous with arteriosclerosis of the intimal type. I propose to discuss atherosclerosis from the pathologist's point of view, to consider the relationship between this disease and diabetes, and to summarize some of the problems that confront investigators in the field of arteriosclerosis.