bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Pubertal Stage and Recent Blood Glucose Control on Plasma Somatomedin C in Children with Insulin-dependent Diabetes Mellitus
Authors: Blethen Sandra L , Sargeant Daniel T , Whitlow Margaret G , Santiago Julio V 
Published: September 2013

One hundred and fifty-five children with insulin-dependent diabetes mellitus were studied to determine the relationship of plasma somatomedin C concentrations to pubertal stage, recent blood glucose control, duration of diabetes, and daily insulin dosage. Plasma somatomedin C, as measured by radioimmunoassay, increased with age and the progression of puberty in both boys and girls, but was not different from those of normal children aged 5–18 yr. In diabetic children under 5 yr of age, plasma somatomedin was significantly lower than in normal children. These results are different from those reported previously in diabetic children, in which somatomedin activity was measured using a pig cartilage bioassay.
In boys, puberty was accompanied by an increase in hemoglobin A1c from 11.6 to 14.1% despite a 36–44% increase in total daily insulin dosage adjusted for body weight. In girls, puberty was also associated with an increase in hemoglobin A1c (12.1–15.1%) without a change in weight-adjusted insulin dose. Although there was no apparent correlation between hemoglobin A1c and somatomedin C in the group as a whole (r = −0.078), multiple regression analyses demonstrated a significant negative correlation between these two variables (P &lt; 0.001) when considered independently of age, sex, pubertal stage, duration of diabetes, and insulin dose. Pubertal status had a significant (P &lt; 0.01) effect on plasma somatomedin C; plasma somatomedin C was also significantly positively correlated with the duration of diabetes (P &lt; 0.01) but not with weight adjusted insulin dose. SMC concentration was not correlated with age when this variable was considered independently of puberty (P = 0.26). The data indicate that puberty and metabolic control both have significant yet independent effects on somatomedin C in children with insulin-dependent diabetes. In addition, the increased somatomedin C associated with puberty may contribute to the accelerated development of diabetic complications seen at this time, while the lowering of somatomedin C associated with worsening metabolic control may adversely affect linear growth.
A New Genetically Obese-Hyperglycemic Rat (Wistar Fatty)
Authors: Ikeda Hitoshi , Shino Akio , Matsuo Takao , Iwatsuka Hisashi , Suzuoki Ziro 
Published: September 2013

The fa-gene was transferred from the Zucker rat (13 M strain) to the Wistar Kyoto (WKY) rat. The survey, performed at the 10th generation of backcrossing, showed that Wistar fatty rats (fa/fa), a congenic strain of WKY, developed obesity and obesity-related features, such as hyperinsulinemia and hyperlipemia, in the same manner as Zucker fatty rats. Males, but not females, showed hyperglycemia, glucosuria, and polyuria as early as 8 wk of age. Tolerance and insulin response to oral glucose were decreased with advancing age in males.
The diabetic changes appeared to be caused by an interaction between predisposition to develop diabetes in the WKY rat and fa-induced obesity. This is because WKY rats were found to be less sensitive to insulin than Zucker rats by both the glucose tolerance test and the steady-state blood glucose method which estimates overall insulin sensitivity.
Effect of Insulin and Glucose Infusions on Sympathetic Nervous System Activity in Normal Man
Authors: Rowe John W , Young James B , Minaker Kenneth L , Stevens Arthur L , Pallotta Johanna , Landsberg Lewis 
Published: September 2013

Recent studies indicate a link between carbohydrate intake and the functional state of the sympathetic nervous system. Fasting or carbohydrate restriction decreases sympathetic activity, while glucose ingestion or dietary supplementation with sucrose increases sympathetic nerve activity. To examine the potential contributions of hyperglycemia and hyperinsulinemia to sympathetic stimulation, sympathetic activity was assessed by measurement of plasma norepinephrine (NE) levels and concomitant cardiovascular indices in nonobese young men during glucose and insulin infusions using glucose clamp techniques. In the insulin infusion studies (euglycemic glucose clamp), insulin was administered at 2 mU/kg/min and 5 mU/kg/min for 2 h while blood glucose was maintained at basal levels by a variable rate of glucose infusion. In the hyperglycemic studies, blood glucose was raised 125 mg/dl above basal and maintained at that level for 2h.
In response to both insulin infusions, plasma NE rose progressively over the course of the study, increasing 50% with the 2-mU infusion (from mean basal value of 240 ± 34 pg/ml to 360 ± 41 at 150 min, P &lt; 0.001 for changes over time by analysis of variance) and 117% with the 5-mil infusion (from 254 ± 20 pg/ml to 551 ± 88 at 150 min, P &lt; 0.001). The plasma NE response was greater with the 5-mll than with the 2-mU insulin infusion (P &lt; 0.001), and similarly, was greater during the 2-mU insulin infusion than during a control test in which neither insulin nor glucose was infused (P &lt; 0.001). Associated with the elevations in plasma NE In the 2-mU insulin infusion were increases in pulse rate (P &lt; 0.05), pulse pressure (P &lt; 0.005), and pulse rate - systolic blood pressure product (P &lt; 0.01), and during the 5-mU insulin infusions there were increases in pulse pressure (P &lt; 0.001), mean arterial blood pressure (P &lt; 0.001), and pulse rate - systolic blood pressure product (P &lt; 0.001). Plasma NE did not change during the hyperglycemic glucose clamp nor during control tests, and pulse pressure in the hyperglycemic studies (P &lt; 0.005) was the only cardiovascular measurement increased by these two infusion protocols. The clearance of NE in three subjects was unaffected by the 2-mU insulin infusion. Thus, insulin infusion increases sympathetic nervous system activity in the absence of changes in blood glucose.
Insulin Release In Vitro from Islet Tissues and Adenomas of Rats Treated with Nicotinamide and Streptozotocin: The Effects of Glucose
Authors: Frigo I , Younoszai R , Dixit P K , Matta S G , Bauer G E 
Published: September 2013

Young male Holtzman rats injected with nicotinamide and streptozotocin develop grossly visible tumors of pancreatic islet tissue. Using ah i.v. glucose tolerance test, some tumor-bearing animals exhibited a vigorous (or fast) response to glucose loading (Diabetic Index = 0.47), whereas others showed a subdiabetic (or slow) response (Diabetic Index = 2.34). In vitro perifusion studies demonstrate that tumor pieces from both groups of rats released immunoreactive insulin (IRI) in response to glucose; tumors from fast responding rats showed a rapid monophasic release of IRI (i.e., rapid transient release with little secondary phase), while tumors from slow responders released IRI in a biphasic pattern resembling that of normal islets.
A population of large islet masses (or microscopic tumors), isolated from drug-treated rats by collagenase digestion of the pancreas of tumor-containing rats, exhibited glucose-stimulated IRI release that resembled the pattern of the tumor from the same animal. Isolated islets of Langerhans of ordinary size from the pancreas of tumor-bearing rats, on the other hand, usually exhibited a normal (biphasic) IRI release pattern in response to glucose. Analysis by gel filtration suggests that the predominant form of IRI released from perifused tumor preparations, under either basal or glucose-stimulated conditions, eluted at a rate corresponding to rat insulin.
Alteration of Glycolytic Intermediary Metabolism in Erythrocytes During Diabetic Ketoacidosis and Its Recovery Phase
Authors: Kono Norio , Kuwajima Masamichi , Tarui Seiichiro 
Published: September 2013

The concentrations of glycolytic intermediates and adenine nucleotides were determined in erythrocytes from patients with diabetic ketoacidosis before and during insulin treatment. Ketoacidosis resulted in an increase in the levels of intermediates above the phosphofructokinase (PFK) step and a marked decrease in the levels of those below this step. Thus, a “crossover” point was seen at the PFK step in a crossover plot. This indicated that the rate of glycolytic flow during ketoacidosis was controlled by PFK and that the reduced level of 2,3-bisphosphoglycerate (2, 3-BPG) was attributed to the inhibition of this enzyme. In vitro studies revealed that acidemia is mainly responsible for the inhibition of PFK, whereas elevated levels of ketone bodies and free fatty acids have no direct bearing on it.
Insulin administration produced hypophosphatemia within 8–12 h and it persisted for 24 h or longer. The levels of fructose-6-phosphate and glucose-6-phosphate were decreased transiently during this hypophosphatemic phase, while those of fructose bisphosphate and triose phosphates were increased. This indicated that PFK was activated. Thus, it is no longer reasonable to think that the inhibition of PFK is a factor responsible for a delay in normalization of the 2, 3-BPG level during the recovery phase. The levels of these glycolytic intermediates, including 2, 3-BPG, were normalized within 4 days by appropriate therapy.
Kinetic Analysis of the Response of Plasma Glucose, Insulin, and C-Peptide to Glucagon Injection in Normal and Diabetic Subjects
Authors: Turco Gianluigi , Brossa Claudio , D'alberto Micaela , Regis Giorgio , Segre Giorgio , Bianchi Enrica , Bruni Bruno , Gamba Silvia 
Published: September 2013

A compartmental model formed by plasma glucose, proinsulin, insulin, and C-peptide was proposed to allow a quantitative evaluation of the interrelationship among the different components of the system and to obtain a better discrimination between normal and pathologic subjects. In 11 control subjects, in 6 mild diabetics, and in 9 severe diabetics (insulin-dependent), the kinetics of plasma glucose, insulin, and C-peptide after an i.v. injection of glucagon (sampling for about 120 min) were fitted to the model which was solved with digital computing techniques. Since biphasic plasma insulin and C-peptide kinetics were demonstrated in many normals and mild diabetics, the effect of glucagon in the model was represented by a differential plus a proportional effect. The model (formed by 6 compartments and 14 transfer constants) takes into account the fact that insulin and C-peptide derive monomolecularly from proinsulin and that liver inactivates insulin.
The values of the parameters obtained were submitted to stepwise discriminant analysis in order to obtain their relative importance in discriminating among the three groups of subjects.
With respect to normal subjects, we found in diabetics an increased inflow of glucose into plasma; a decreased effect of glucagon in promoting the proinsulin response; a decreased effect of glucose in promoting the proinsulin response; a decreased glucose utilization; a lower coupling effect of insulin on glucose; and a higher disappearance rate of C-peptide. We observed a lower formation of insulin and C-peptide from proinsulin in severe diabetics.
Diabetic Retinopathy in Identical Twins
Authors: Leslie R D G , Pyke D A 
Published: September 2013

The prevalence and features of diabetic retinopathy have been examined in 95 pairs of identical twins, 31 concordant for insulin-dependent diabetes (IDD), 27 discordant for IDD, and 37 concordant for non-insulin-dependent diabetes (NIDD). Optic fundi were examined after pupillary dilatation and retinopathy was classified as nil, background, or severe. In the NIDD twins, 35 of the 37 pairs were in the same category including all but one of the 15 pairs with the same duration of diabetes. However, in insulin-dependent diabetic pairs the situation was quite different; only 21 of 31 pairs were in the same retinopathy category, and of the 10 pairs of co-twins with the same duration of diabetes 5 pairs showed a striking difference for retinopathy. There was no significant difference in the prevalence of retinopathy in the concordant and discordant IDD twin pairs. Diabetic retinopathy was not observed in 32 unaffected co-twins of diabetics.
We conclude that genetic factors may be important in the etiology of retinopathy in non-insulin-dependent diabetes but that nongenetic factors must be important in the pathogenesis of retinopathy in insulin-dependent diabetes.
Reversal of Abnormalities in Ocular Fluorophotometry in Insulin-dependent Diabetes After Five to Nine Months of Improved Metabolic Control
Authors: White Neil H , Waltman Stephen R , Krupin Theodore , Santiago Julio V 
Published: September 2013

Abnormalities in ocular fluorophotometry occur in human and experimental diabetes mellitus. To determine the reversibility of these abnormalities, we studied prospectively 11 intensively treated and 25 conventionally treated insulin-dependent diabetics (IDD) preselected because of abnormal vitreous fluorophotometry. Among the 25 IDD treated conventionally with one or two insulin injections daily, hemoglobin A1C concentrations remained elevated and fluorescein concentration, 1 h after the intravenous injection of fluorescein (7 mg/kg), did not change significantly in either the anterior chamber or the posterior vitreous.
Among 11 IDD treated intensively with home blood glucose monitoring and pumped subcutaneous insulin or three or more injections daily, hemoglobin A1C fell dramatically (10.4 ± 0.7% to 7.5 ± 0.2%) and anterior chamber fluorescein concentration decreased (73.9 ± 7.7 to 49.5 ± 5.3 ng/ml). Two patients with proliferative retinopathy showed no improvement in their massive vitreous fluorescein accumulation and subsequently required photocoagulation. In the nine subjects without proliferative retinopathy, vitreous fluorescein accumulation decreased in eight (10.6 ± 0.7 to 6.5 ± 0.5 ng/ml) and was normal in six after 1 yr. The only subject with increasing vitreous fluorescein accumulation also had concurrent worsening of background retinopathy.
These studies support the hypothesis that moderate abnormalities in ocular fluorophotometry are due to reversible changes in ocular tissues, such as retinal pigment epithelium. Fluorescein leakage emanating from the advanced vascular or retinal abnormalities of proliferative retinopathy were not reversed with the degree and duration of metabolic control achieved in the present study. The long-term significance of the reversal of moderate abnormalities in fluorophotometry is not clear at the present time.
Insulin Resistance in Diabetic Ketoacidosis
Authors: Barrett Eugene J , DeFronzo Ralph A , Bevilacqua Stefano , Ferrannini Eleuterio 
Published: September 2013

The effect of “low-dose” (6–10 U/h) insulin treatment on the rate of decline of plasma glucose concentration was determined in 15 diabetic subjects admitted in ketoacidosis (plasma glucose = 948 ± 79 mg/dl) and in six normal volunteers rendered hyperglycemic by a combined infusion of somatostatin and glucose (plasma glucose = 653 ± 28 mg/dl). The fractional glucose turnover and the half-time of the fall in plasma glucose during insulin treatment were both 10-fold reduced (P &lt; 0.001) in the diabetics as compared with the controls. In the ketoacidotic subjects, the mean glucose clearance during insulin treatment was only 8% of that in the controls (P &lt; 0.001). In the normal subjects, tissue glucose clearance during insulin treatment of the hyperglycemia (5.8 ± 0.7 ml/min · kg) was similar to that measured in the same subjects using a standard technique to quantitate insulin sensitivity (euglycemic insulin clamp).
In the ketoacidotic patients, a history of prior insulin therapy, but not the degree of hyperglycemia at the time of admission, was associated with a more rapid rate of decline of plasma glucose in response to insulin treatment. We conclude that marked insulin resistance is present in virtually all diabetics in ketoacidosis.
In Vivo Deactivation of Peripheral, Hepatic, and Pancreatic Insulin Action in Man
Authors: Gray R S , Scarlett J A , Griffin J , Olefsky J M , Kolterman O G 
Published: September 2013

The in vivo deactivation of insulin action has been studied in 10 lean, nondiabetic subjects using a modification of the euglycemic glucose clamp technique. Following cessation of 40- and 120-mU/m2/min insulin infusions, the serum insulin levels fell to one-half their initial values (mean ± SE) of 126 ± 7 and 350 ± 14 μU/ml in 7 ± 1 and 8 ± 1 min, respectively. The mean incremental glucose disposal rates (IGDR) fell more slowly following discontinuation of the 40- and 120-mU/m2/min insulin infusions, so that the time required for the IGDRs to fall to one-half their initial values (D50 IGDR) were were 42 ± 5 and 78 ± 5 min, respectively. Mean hepatic glucose output was totally suppressed during the 40- and 120-mU/m2/min insulin infusions, remained completely suppressed following cessation of the infusions for 50 and 80 min, and subsequently returned to basal levels. The times required for the HGOs to return to one-half their basal levels (R50 HGO) were 59 ± 8 and 119 ± 6 min, respectively. The times required for insulin action to decrease to one-half the initial values in the periphery (D50 IGDR) and in the liver (R50 HGO) were correlated with the preceding steady-state glucose disposal rates in individual subjects (r = 0.75, P &lt; 0.001 and r = 0.58, P &lt; 0.05, respectively). The suppression of endogenous insulin secretion by exogenous insulin infusions was also studied in 4 subjects during a total of 5 euglycemic glucose clamps; the mean basal serum C-peptide level was 0.67 ± 0.24 pmol/ml before administration of the exogenous insulin, fell to 0.34 ± 0.17 pmol/ml during the steady-state phase of the study, and remained suppressed throughout the duration of the deactivation phase of the glucose clamp. Residual pancreatic insulin secretory capacity was demonstrated by a rise in the serum C-peptide level to 1.77 ± 0.50 pmol/ml at 120 min following a standardized meal given at the conclusion of the deactivation phase of the glucose clamp.
These results demonstrate that the deactivation of insulin action in the periphery, liver, and pancreas lags behind the disappearance of insulin from the plasma. The mechanisms responsible for this lag in in vivo deactivation are not known for certain, but may include slower clearance of insulin form tissue compartments than form the plasma, the necessity for the target tissues to generate specific deactivation signals, or a slow rate of decay of saturable steps in the cellular activation process.
Decreased Insulin Binding, Glucose Transport, and Glucose Metabolism in Soleus Muscle of Rats Fed a High Fat Diet
Authors: Grundleger Melvin L , Thenen Shirley W 
Published: September 2013

The relationship between diet and insulin sensitivity was examined in isolated soleus muscle from 10-wk-old lean Zucker rats. Rats were fed either a high fat or high carbohydrate diet that had 67% of calories as fat or carbohydrate, respectively, for 10 days. Plasma insulin but not plasma glucose concentrations were significantly elevated in high-fat-fed rats, indicating that a state of insulin resistance existed. The mechanisms responsible for the insulin resistance were studied by measuring insulin binding, 2-deoxyglucose uptake, and glucose metabolism in soleus muscle. The soleus muscle from the high-fat-fed rats bound significantly less insulin than high carbohydrate control rats under equilibrium binding conditions. The 35% decrease in insulin binding at maximal insulin concentrations resulted from a decrease in insulin receptor number but no change in receptor affinity. Maximal insulin-stimulated 2-deoxyglucose uptake was reduced in soleus muscle from high-fat-fed rats when compared with high carbohydrate controls.
A decrease in postmembrane basal and insulin-stimulated glucose utilization was produced by high rat feeding and varied depending upon the pathway involved. An estimate of glycolysis (3H2O) formation from [5-3H]glucose) and glucose oxidation (14CO2 production from 14C-glucose) demonstrated a greater decrease in basal and insulin-stimulated utilization than in [5-3H]glucose conversion to [3H]glycogen. These results suggest that multiple sites are responsible for the observed insulin resistance in soleus muscle after high fat feeding.
Nonenzymatic Browning via the Maillard Reaction in Foods
Authors: Saltmarch Miriam , Labuza Theodore P 
Published: September 2013

Nonenzymatic glycosylation of human hemoglobin has recently received increased attention because of its relevance to diabetes mellitus. The reaction of carbohydrates and protein, often called the Maillard reaction, is well known in the food industry. The Maillard reaction is actually a complex scheme of many reactions and is the primary type of nonenzymatic browning that can occur in dehydrated or semimoist foods during storage. This reaction results from reducing compounds, primarily sugars, reacting with proteins, peptides, amino acids, or free amine groups and results in changes in the aesthetic, functional, and nutritional properties of the food in which the reaction occurs.
In the present review, no attempt is made to cover all the literature. Rather, attention is given to the various chemical and physical factors that can affect the Maillard reaction in foods. Chemical factors include the type and amount of initial reactant species, pH, water content or water activity, and the presence of substances such as liquid humectants and bisulfite. In addition physical factors such as processing and storage temperature, atmospheric oxygen, and packaging during storage can affect the Maillard reaction in foods.
Transplantation of Islets and Bone Marrow Cells to Animals with Immune Insulitis
Authors: Naji Ali , Bellgrau Donald , Anderson Arthur , Silvers Willys K , Barker Clyde F 
Published: September 2013

The results of islet transplantation in an animal model of spontaneous immune insulitis were studied to see whether this disease process might damage transplanted tissue. Since the insulitis occurs only in “BB” rats (which are not genetically uniform) syngeneic grafts could not be used, therefore allograft rejection was avoided by rendering “BB” rats tolerant of WF transplantation antigens by inoculating them neonatally with WF bone marrow cells. Despite the resultant tolerant state, which permitted successful engraftment of WF skin and islets transplanted to artificially diabetic “BB” rats, tolerant “BB” rats with spontaneous diabetes accepted transplanted WF islets only briefly before they were destroyed by immune insulitis.
“BB” rats were found to have abnormalities in immune response (delayed skin graft rejection and decreased alloreactivity in mixed lymphocyte response). However, the immune response was more normal in “BB” rats that were treated neonatally with WF bone marrow. Moreover, “BB” rats inoculated with WF bone marrow neonatally were found less likely to become diabetic than untreated “BB” controls. It is suggested that the chimeric state (persistence of WF bone marrow cells) may be responsible for the improved immune response and perhaps for the decreased susceptibility to diabetes.