bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Heparin on Insulin Binding and Biological Activity
Authors: Kriauciunas Kristina M , Grigorescu Florin , Kahn C Ronald 
Published: September 2013

The effect of heparin, a potyanionic glycosaminoglycan known to alter the function of many proteins, on insulin binding and bioactivity was studied. Cultured human lymphocytes (IM-9) were incubated with varying concentrations of heparin, then extensively washed, and 125I-labeled insulin binding was measured. Heparin at concentrations used clinically for anticoagulation (1-50 U/ml) inhibited binding in a dose-dependent manner; 50% inhibition of binding occurred with 5-10 U/ml. Scatchard analysis indicated that the decrease in binding was due to a decrease in both the affinity and the apparent number of available insulin receptors. The effect occurredwithin 10 min at 22°C and persisted even after the cells were extensively washed. Inhibition of insulin binding also occurred when cells were preincubated with heparinized plasma or heparinized serum but not when cells were incubated with normal serum or plasma from blood anticoagulated with EDTA. By contrast, other polyanions and polycations, e.g., poly-L-glutamic acid, poly-L-lysine, succinylated poly-L-lysine, and histone, did not inhibit binding.
Heparin also inhibited insulin binding in Epstein-Barr (EB) virus-transformed lymphocytes buthad no effect on insulin binding to isolated adipocytes, human erythrocytes, or intact hepatoma cells. When isolated adipocytes were incubated with heparin, there was a dose-dependent inhibitionof insulin-stimulated glucose oxidation and, to a lesser extent, of basal glucose oxidation. Although heparin has no effect on insulin binding to intact hepatoma cells, heparin inhibited both insulin binding and insulin-stimulated autophosphorylation in receptors solubilized from these cells. These data indicate that heparin may interact with insulin receptors at concentrations normally used for anticoagulation, altering insulin binding and/or action in various cell types.
Studies of Midaglizole (DG-5128): A New Type of Oral Hypoglycemic Drug in Healthy Subjects
Authors: Kawazu S , Suzuki M , Negishi K , Watanabe T , Ishii J 
Published: September 2013

Midaglizole (DG-5128), 2-[2-(4,5-dihydro-1H-imidazol-2- yl)-1-phenylethyl]pyridine dihydrochloride sesquihydrate, is a novel α2-adrenoceptor antagonist. Its effects on plasma glucose, immunoreactive insulin (IRI), and immunoreactive glucagon (IRG) in healthy male volunteers were investigated.
Volunteers received single oral administrations of midaglizole (150–500 mg), multiple increasing oral administrations on 3 separate days (150–300 mg 3 times daily), or successive daily oral administration for 1 wk (200 mg 3 times daily).
The hypoglycemic action of midaglizole was observed within 0.5–1.0 h after its administration and thereafter for 5 h. The maximum hypoglycemic effect was found 1.0–1.5 h after administration. Midaglizole decreased postprandial hyperglycemia ina dose-dependent manner. In the fasting state, midaglizole significantly increased IRI secretion and suppressed IRG secretion. Midaglizole inhibited epinephrine-induced platelet aggregation after successive administration for 1 wk (200 mg 3 times daily).
The plasma half-life of midaglizole was only 3 h, and the drug was rapidly excreted into the urine and feces, with &gt;80% in its unchanged form, within 24 h.
Midaglizole did not affect the results of any clinical or laboratory tests performed. Our data indicate that midaglizole is a possible hypoglycemic agent. Further clinical investigations are required to confirm its effects on diabetes mellitus.
Autonomic Neuropathy in BB Rat: Assessment by Improved Method for Measuring Heart-Rate Variability
Authors: McEwen Tom A J , Sima Anders A F 
Published: September 2013

Sinus arrhythmia is a normal respiration-related variation in heart rate that is diminished or absent in autonomic nerve dysfunction. The conventionally used measurements, R-R intervals and their standard deviations (RRSD), were made and compared with a computed statistic () in spontaneously diabetic BB rats and in age-matched nondiabetes-prone control rats. In addition, the effects of pentobarbital sodium anesthesia on RRSD and values in normal control rats were compared with those of nonanesthetized animals.
BB rats demonstrated a decrease in values after 8 wk of diabetes. This decrease became more marked with increased duration of diabetes. No differences in mean R-R intervals or RRSD were obtained between diabetic and nondiabetic rats until 24 wk of diabetes. Normal control rats showed a decrease in sinus arrythmia with age. Both RRSD and values were greatly decreased in anesthetized animals.
Quantitative Analysis of Pancreatic Proinsulin mRNA in Genetically Diabetic (db/db) Mice
Authors: Orland Matthew J , Permutt M Alan 
Published: September 2013

C57BL/KsJ db/db mice develop hyperphagic obesity and nonketotic diabetes similar to non-insulin-dependent diabetes mellitus in humans. Initially the mice demonstrate an abundant β-cell mass and hyperinsulinemia, which is followed by apparent β-cell loss. As an index of insulin synthesis, this study assesses pancreatic proinsulin mRNA, measured by dot hybridization to cloned cDNA, during the development of diabetes in the mice. Changes in proinsulin mRNA from 5 to 13 wk of age are compared with serum insulin, pancreatic insulin content, and blood glucose. In control (+ /db) mice, total proinsulin mRNA and pancreatic insulin content increased with age. Both changes were proportional to an increase in body weight. Obesity, hyperglycemia, and hyperinsulinemia were evident in diabetic (db/db) mice at 5 wk of age. Although pancreatic insulin content was comparable to that in the + /db controls at 5 wk, a fourfold relative elevation of proinsulin mRNA was observed. Despite an increase in body weight, proinsulin mRNA concentration and total proinsulin mRNA fell to levels similar to those of the control mice at 10 and 13 wk, associated with a loss of hyperinsulinemia, a mild decrease in pancreatic insulin content, and a marked increase in fasting blood glucose. A separate group of db/db mice was pair fed with the + /db controls from 4 to 13 wk. These diet-restricted diabetic mice were heavier than control mice and gained weight with age, but they weighed less than the unrestricted mice at all ages. Compared with the unrestricted db/db mice, a more modest fasting hyperglycemia was apparent, and a persistent hyperinsulinemia was observed. This group also preserved a high proinsulin mRNA concentration and showed a less marked fall in total proinsulin mRNA. Pancreatic insulin content was lower than that of controls, but a modest increase occurred with age.
A strong correlation between serum insulin and total proinsulin mRNA is apparent in this study. Hyperinsulinemia in young diabetic mice is associated with abundant proinsulin mRNA, but occurrence of hyperglycemia and reduced pancreatic insulin content suggests that the ability to augment insulin synthesis is limited and insufficient to meet metabolic needs. The deterioration of hyperinsulinemia with age, accompanying more profound fasting hyperglycemia, is associated with a reduction of insulin synthesis reflected by a decreased total proinsulin mRNA. The loss of insulin synthetic capacity in these diabetic mice can be lessened by diet restriction, suggesting that the maintenance of total proinsulin mRNA in diet-restricted db/db mice may be important in ameliorating their diabetic state.
Glyburide Sensitizes Perfused Rat Liver to Insulin-Induced Suppression of Glucose Output
Authors: McGuinness Owen P , Green Donald R , Cherrington Alan D 
Published: September 2013

Glyburide, a second-generation sulfonylurea, is used in the treatment of NIDDM because of its hypoglycemic action. However, the site and mechanism of action of this sulfonylurea remain unclear. We examined the ability of glyburide to enhance insulin's inhibitory effect on glucagon-stimulated hepatic glucose production.
The livers of fed male rats were perfused with a Krebs-Henseleit buffer containing washed human red blood cells. After a 60-min control period during which the liver was exposed to both insulin and glucagon (10 μU/ml and 11 pg/ml, respectively), the glucagon concentration was increased to 88 pg/ml in the presence of 0, 10, 40, and 240 μU/ml of insulin. Hepatic glucose output and phosphorylase a activity were monitored during the control and elevated-glucagon periods. The glyburide-infused group received glyburide (1.6 μg/ml) during both the control and elevated-glucagon periods. As expected, high levels of insulin suppressed glucagon- stimulated glucose production and phosphorylase activation. Insulin at a concentration of 10 μU/ml was unable to suppress glucagon's stimulation of glucose production or its activation of phosphorylase. However, in the presence of glyburide it was able to decrease stimulated hepatic glucose production and phosphorylase activation by 40 and 50%, respectively. In the absence of insulin, glyburide was unable to suppress glucagon's glycogenolytic action, suggesting that the drug potentiates insulin's action on the liver rather than exerting an inhibitory effect directly. Insulin at a concentration of 240 μU/ml completely suppressed glucagon action, and glyburide had no additional effect. Therefore, glyburide is able to enhance the sensitivity of the perfused rat liver to insulin with-out altering maximal insulin responsiveness.
Involvement of Endogenous Opiates in Glucose-Stimulated Hyperinsulinism of Canine Endotoxin Shock: Inhibition by Naloxone
Authors: Merrill Gerald A , Anderson James H 
Published: September 2013

Hyperinsulinism has been associated with infection and endotoxin shock in rodents, dogs, and humans. In dogs with Escherichia coli-induced endotoxin shock, this hyperinsulinism was in response to glucose administration.
To determine the role of endogenous opiates in endotoxin-induced glucose-stimulated hyperinsulinism, plasma β-endorphin, Met-enkephalin, Leu-enkephalin, insulin, and glucose concentrations were measured for 6 h in fasted, anesthetized dogs given 1) LD70 of E. coli endotoxin; 2) endotoxin and glucose; 3) endotoxin, glucose, and naloxone (an opiate antagonist); 4) glucose and naloxone; or 5) glucose alone.
Plasma endogenous opiate immunoreactivity was elevated in dogs that received endotoxin, regardless of the presence of glucose or naloxone. The elevation of plasma Met-enkephalin and β-endorphin preceded the onset of hyperinsulinism, but the elevation of plasma Leu-enkephalin did not. Plasma insulin was elevated 100-fold by 360 min in dogs given endotoxin and glucose. The magnitude of this hyperinsulinism was markedly reduced by naloxone, supporting the hypothesis that endogenous opiates are involved in the development of the glucose-stimulated hyperinsulinism associated with endotoxin shock. Interestingly, naloxone, given in conjunction with glucose, appeared to have a stimulatory effect on insulin secretion.
Insulin Treatment Improves Glucose-Induced Insulin Release in Rats With NIDDM Induced by Streptozocin
Authors: Kergoat Micheline , Bailbe Danielle , Portha Bernard 
Published: September 2013

Insulin-deficient diabetes in humans, as well as in the neonatal streptozocin-induced rat model of non-insulin-dependent diabetes mellitus (NIDDM), are associated with islet β-cell insensitivity to glucose. We hypothesized that the chronic hyperglycemia- -hypoinsulinemia pattern causes this impairment of the glucose influence on insulin secretion. This study was designed to determine whether the glucose defect could be counteracted by normalizing the diabetic state in rats with NIDDM after insulin therapy. Mixte lente insulin (5 U · kg−1 · day−1) was given daily at 1700 h over 24 h or 5 consecutive days. Insulin secretion was studied the morning after the last insulin injection with the isolated perfused pancreas preparation. Fed basal plasma glucose levels decreased in diabetic rats from 183 ± 8 to 136 ± 10 mg/dl after the 1-day insulin treatment and to 135 ± 5 mg/dl after the 5-day insulin treatment (vs. 116 ± 3 mg/dl in control rats). Pancreatic insulin stores were not affected by insulin therapy.
Although the 1-day insulin treatment did not modify the lack of glucose response in the diabetic rats, the 5-day insulin treatment improved their glucose-induced insulin secretion. Moreover, insulin therapy improved the priming effect of glucose on a second stimulation with glucose. The return of this glucose effect was hardly detectable after the 1-day insulin therapy but was clearly present after the 5-day treatment. The hyperresponse to arginine, characteristic of the untreated diabetic rat, returned similar to that in controls after a 1-day insulin therapy, and it was again amplified at high glucose levels, although amplification remained lower than that of control rats. This indicates that the potentiating effect of glucose on the response to arginine was regained more precociously than the acute insulin response to glucose after insulin therapy. These data agree with the hypothesis that the chronic hyperglycemia-hypoinsulinemia in the NIDDM rat causes abnormal glucose influence on glucose- and arginine-stimulated insulin release.
Sorbinil Partially Prevents Decreased Erythrocyte Deformability in Experimental Diabetes Mellitus
Authors: Robey Claude , Dasmahapatra Amita , Cohen Margo P , Suarez Sarah 
Published: September 2013

The ability of red blood cells (RBCs) to undergo an adaptation in shape that permits passage through the smallest vessels is reportedly impaired in diabetes. Several hypotheses have been proposed to explain decreased erythrocyte deformability, which has been implicated in the pathogenesis of microvascular complications, but the mechanisms responsible for this change have not been clearly delineated. In view of the fact that sorbitol accumulates in RBCs in diabetes and the postulate that increased sorbitol could alter deformability properties, we examined the influence of the aldose reductase inhibitor sorbinil on erythrocyte deformability.
Erythrocyte deformability, determined as the volume of RBCs (VRBC) filtered per minute through 4.7-μm pore size filters, was significantly reduced in samples from diabetic rats compared with samples from controls (0.76 ± 0.03 vs. 0.97 ± .02 ml RBC/min; P &lt; .001). In contrast, deformability of RBCs from diabetic animals treated with sorbinil was significantly greater than in untreated diabetes, although not completely normalized (0.88 ± 0.02; P &lt; .01 vs. diabetic, and P &lt; .02 vs. control). The reduced deformability characterizing cells from diabetic rats and its partial prevention by sorbinil persisted even when RBCs were washed to eliminate hyperglycemie and hyperviscous plasma. Thus, hyperviscosity per se is not responsible for the decreased deformability, and sorbinil can partially prevent this change despite persistent hyperglycemie. This effect may derive from sorbinil's action as an aldose reductase inhibitor and/or its ability to influence physicochemical properties of the erythrocyte membrane.
Biosynthesis of Proinsulin and Other Islet Cell Proteins in Pancreatic Beta Cells of the Rat: A Radioautographic Evaluation of Glucose Effects In Vitro
Authors: Logothetopoulos John , Jain Kanti 
Published: September 2013

Rat pancreatic islets were incubated in vitro with L-[4,5-3H]leucine or with L-[2,3-3H]tryptophan in Krebs-Ringer bicarbonate buffer, containing 0, 5, or 20 mM glucose. Incorporation of labeled amino acids in islet cells was evaluated quantitatively by a validated radioautographic procedure. Incorporation of labeled leucine into [3H]proinsulin and [3H]insulin was measured by immunoprecipitation and into other islet proteins by trichloroacetic acid precipitation.
Incorporation of labeled amino acids in pancreatic beta cells was patchy and not uniform. Up to 20 to 35% of beta cells, mainly in central regions of the islets, showed poor or no incorporation of label. Peripheral nonbeta, endocrine islet cells and mesenchymal islet cells were all uniformly labeled. Incorporation of either amino acid into nonbeta endocrine and mesenchymal cells was not much affected by the absence of glucose in the incubation buffer. In contrast, incorporation of the amino acids into beta cells was strikingly affected. Incorporation of [3H]leucine into proinsulin and insulin at 0 mM glucose measured by specific immunoprecipitation and by silver grain densities over beta cells was 15 to 20 times less than at 20 mM glucose. Incorporation of [3H]tryptophan, an amino acid absent in proinsulin, into nonhormonal, sedentary beta cell proteins studied by radioautography, similarly, was strikingly affected in the absence of glucose. Thus, radioautography revealed a great sensitivity of both hormonal and nonhormonal protein biosynthesis in the beta cell to the concentration of glucose in the medium.
Glucose-induced Thermogenesis in Nondiabetic and Diabetic Obese Subjects
Authors: Golay A , Schutz Y , Meyer H U , Thiébaud D , Curchod B , Maeder E , Felber J-P , Jéquier E 
Published: September 2013

The glucose-induced thermogenesis (GIT) following a 100-g oral glucose load has been measured by continuous indirect calorimetry in 55 nondiabetic and diabetic obese subjects of various ages and compared with two control groups of 17 young and 13 elderly nonobese subjects. The obese subjects were divided into four groups: group A, normal glucose tolerance; group B, impaired glucose tolerance; group C, diabetes with increased insulin response; group D, diabetes with reduced insulin response.
The glucose-induced thermogenesis measured during 3 h represented 8.6 ± 0.7% of the energy content of the load in the young control group. In all obese groups, the glucose-induced thermogenesis was significantly lower than in the young control group, i.e., 6.6 ± 0.9%, 6.4 ± 0.6%, 3.7 ± 0.7%, and 2.2 ± 0.4% in groups A, B, C, and D, respectively. Since the obese diabetics were older than the other groups, their glucose-induced thermogenesis was compared with that of the elderly control group; the latter (5.8 ± 0.3%) was significantly lower (P &lt; 0.05) than that of the young control group. The obese diabetics also had a significantly lower glucose-induced thermogenesis than the elderly control group (P &lt; 0.02 and P &lt; 0.001 for groups C and D, respectively). When corrected for glucosuria and after taking into account the glucosuria and the changes in the glucose space, the corrected glucose-induced thermogenesis (i.e., related to glucose “uptake”), was still significantly reduced in group A versus the young control group (6.6 ± 0.9 versus 8.6 ± 0.7%, P &lt; 0.05), and in group D versus the elderly (matched for age) control group (4.2 ± 0.7 versus 5.8 ± 0.3%, P &lt; 0.05).
It is concluded that the postprandial thermogenesis induced by glucose ingestion is decreased in the presence of insulin resistance and/or reduced insulin response to the glucose load in obese subjects. In addition, age itself contributes to decrease glucose-induced thermogenesis.
Insulin and Glucagon Release from Cultured Neonatal Pancreatic Islets of Lean and Preobese Zucker Rats
Authors: Hayek Alberto 
Published: September 2013

Pancreatic islets were isolated from individual neonatal (2-5 days of age) lean and preobese Zucker rats to assess insulin and glucagon release after 7 and 14 days of culture. Insulin and glucagon release were elicited with high glucose (22.2 mM) plus aminophylline (10 mM) and alanine (10 mM), respectively.
The similar secretory hormone patterns, both at basal and stimulated conditions, of the islets from rats later identified as lean or obese, suggest that a primary islet defect does not cause the hyperinsulinemia.
Pregnancy-associated Hypertriglyceridemia in Normal and Diabetic Women: Differences in Insulin-dependent, Non-insulin-dependent, and Gestational Diabetes
Authors: Hollingsworth Dorothy R , Grundy Scott M 
Published: September 2013

In this study longitudinal observations of plasma lipo-proteins were made in pregnant diabetic women classified according to the National Diabetes Data Group. Sequential measurements at second trimester (25–27 wk), third trimester (34–37 wk), and 3 mo postpartum (control period) were carried out in 18 diabetic and 6 normal women. In 15 diabetic and 4 normal women from this group, 24-h plasma glucose, serum C-peptide levels, and HbA1c concentrations were measured. Another group of 15 normal and 18 diabetic women underwent determinations of fasting plasma lipoproteine and other parameters at one or more of the test periods.
Insulin-dependent diabetic patients (IDDM, type I) as a group did not differ from normal controls in mean plasma levels of total cholesterol (CHOL), triglyceride (TG), very-low-density lipoprotein triglyceride (VLDL TG), low-density lipoprotein cholesterol (LDL CHOL), high-density lipoprotein cholesterol (HDL CHOL), or ratios of TG:CHOL in LDL or HDL during mid or late pregnancy or 3 mo postpartum. In marked contrast, non-insulin-dependent diabetics (NIDDM, type II) had significantly higher total fasting TG at second trimester (P &lt; 0.005), third trimester (P &lt; 0.03), and postpartum (P &lt; 0.01). VLDL TG levels at the second trimester, third trimester, and postpartum also were higher than in women with IDDM or normals. In NIDDM subjects the accentuated hypertriglyceridemia during second and third trimesters was also apparent in elevated LDL TG:CHOL and HDL TG:CHOL ratios. These differences were not correlated with prepregnancy weight, weight gain during gestation, or diabetic control. Women with gestational diabetes (GDM) also had significantly higher TG levels at second trimester and postpartum. Mean HDL CHOL levels were significantly lower in patients with NIDDM and GDM than in controls and IDDM patients throughout pregnancy and 3 mo postpartum. Two of 21 normals and one woman with IDDM diabetes had spontaneously reversible pregnancy-evoked hypertriglyceridemia.
These results indicate that women with IDDM diabetes do not differ from normal women with respect to pregnancy-associated changes in lipid metabolism. On the other hand, women with NIDDM and GDM exhibit a pregnancy-associated hypertriglyceridemia.
An Economic Comparison of Pesticide Applications for Processing and Table Tomatoes: A Case Study for Turkey
Authors: Engindeniz Sait , Cosar Gorkem Ozturk 
Published: September 2013

Abstract
In many circumstances, pesticides are the only effective means of controlling disease organisms, weeds, or insect pests. Yet, pesticides are toxic and potentially hazardous to humans, other animals and organisms, and the environment. Therefore, people who use pesticides or regularly come in contact with them must understand the relative toxicity, potential health effects, and preventative measures to reduce the exposure to the products they use. Today, farm-level costs include the costs of the pesticides, and their application. This study was conducted to analyse the farm-level economics of pesticide use on the processing and table tomato growing in selected regions of Turkey. Data was collected from 59 processing tomato farmers and 30 table tomato farmers. These farmers were willing to have their data recorded. According to the results of the study, the average usage concerning the active ingredient of pesticides for the processing and table tomatoes were 4,825.02 and 5,273.86 g/ha. Average pesticide and pesticide application costs of the processing and table tomatoes were determined to be $445/ha and $502/ha, respectively. The breakeven yields for the processing and table tomatoes were calculated to be 3,708 and 3,138 kg/ha, repectively.