bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Diabetes on Triiodothyronine and Reverse Triiodothyronine Production in the Perfused Rat Liver and Kidney
Authors: Ikeda Tadasu , Ito Yasuo , Murakami Isao , Mokuda Osamu , Kuno Satoru , Tokumori Yutaka , Tominaga Masato , Mashiba Hiroto 
Published: September 2013

This study was undertaken to elucidate the effect of diabetes on the conversion of T4 to T3 and rT3 in the isolated, perfused rat liver and kidney. The livers and kidneys from streptozocin (STZ)-induced (50 mg/kg i.p. 2 wk before killing) diabetic rats with or without T4 (30 μg/kg s.c. daily) treatment were perfused for 30 min with a synthetic medium containing T4 (6 μg/dl), and production of T3 and rT3 in the tissues was measured by radioimmunoassay.
The production of T3 (111 ± 38 ng/g/30 min, mean ± SD) and conversion rate of T4 to T3 (19.7 ± 5.8%) in the liver of diabetic rats without T4 treatment and those (124 ± 41 ng/g/30 min and 21.6 ± 4.9%) in the liver of diabetic rats with T4 treatment were significantly lower than those of controls (196 ± 48 ng/g/30 min and 30.6 ± 5.2%), respectively. The production of rT3 and conversion rate of T4 to rT3 in the liver of diabetic rats with or without T4 treatment were similar to those of controls.
The production of T3 and rT3, and conversion rate of T4 to T3 and T4 to rT3, in the kidney of diabetic rats with or without T4 treatment were not significantly different from those of controls.
These results suggest that the liver is far more important than the kidney in the overall reduction in the T4 to T3 conversion that occurs in diabetic rats.
Sorbinil Prevents Diabetes-induced Increases in Vascular Permeability But Does Not Alter Collagen Cross-Linking
Authors: Williamson Joseph R , Chang Katherine , Rowold Edwin , Marvel Joyce , Tomlinson Martha , Sherman William R , Ackermann Karen E , Kilo C 
Published: September 2013

In recent studies we have demonstrated a marked increase in albumin permeation of new vessels formed by angiogenesis (in subcutaneous tissue) in the diabetic milieu. Likewise, lysyl oxidase-mediated collagen cross-linking is markedly increased in the scar tissue associated with angiogenesis. The present studies were undertaken to determine whether sorbinil, a chemical inhibitor of aldose reductase that has been shown to prevent and reverse diabetic cataracts and neuropathy, also could prevent the vascular permeability and collagen cross-linking changes in this model. Vascular permeation by 125I-BSA, collagen cross-linking, and tissue levels of sorbitol, myo-inositol, and scyllo-inositol were assessed in male Sprague-Dawley rats 3 wk after injection of streptozocin and induction of angiogenesis and collagen synthesis in polyester fabric implanted subcutaneously.
Sorbinil (∼25 mg/kg/day) added to the diet of diabetic rats reduced the diabetes-induced increases in albumin permeation by 80%, completely prevented diabetes-induced changes in tissue levels of sorbitol and myo-inositol, and markedly reduced diabetes-induced changes in tissue levels of scyllo-inositol. In contrast, sorbinil had no effect on plasma glucose levels or collagen solubility (an index of collagen cross-linking). These observations indicate that increased vascular permeability associated with diabetes is linked to imbalancesin sorbitol/inositol metabolism. These findings also indicate that (1) diabetes-induced increases in vascular permeability and in collagen cross-linking are independent phenomena and (2) diabetes-induced increases in vascular permeability are largely preventable by treatment with an aldose reductase inhibitor in the face of high plasma glucose levels.
Comparison of Insulin-mediated and Glucose-mediated Glucose Disposal in Patients with Insulin-dependent Diabetes Mellitus and in Nondiabetic Subjects
Authors: Hansen I L , Cryer P E , Rizza R A 
Published: September 2013

To determine whether glucose-mediated as well as insulin-mediated regulation of glucose utilization and glucose production is impaired in patients with insulindependent diabetes mellitus (IDDM), six nonobese, diabetic patients and seven age-, sex-, and weightmatched nondiabetic subjects were studied. Despite slightly higher free insulin concentrations in the diabetic patients than in the nondiabetic subjects during 0.2 mU/kg · min (22 ± 3 versus 15 ± 2 μU'ml) and 1.0 mU'kg · min (98 ± 10 versus 75 μU/ml) insulin infusions, glucose utilization at plasma glucose concentrations of 95, 135, and 175 mg/dl was lower in the diabetic patients than in the nondiabetic subjects. The increment in glucose utilization per increment in plasma glucose (i.e., slope) in the diabetic and nondiabetic subjects, respectively, did not differ significantly during either the 0.2 (1.7 ±1.3 versus 1.4 ± 0.5 dl/kg · min) or 1.0 (4.4 ±1.1 versus 6.2 ±1.0 dl/kg · min) mU/kg · min insulin infusions, although they tended to be higher in the nondiabetic subjects during the latter infusion.
Thus, although stimulation of glucose utilization by insulin is impaired in patients with IDDM, the ability of an increase in glucose concentration to increase glucose utilization does not appear to differ from that present in nondiabetic subjects, at insulin concentrations in the low physiologic range. Whether differences exist in the high physiologic range remains to be determined.
Glucose-stimulated DNA Replication of the Pancreatic Islets During the Development of the Rat Fetus: Effects of Nutrients, Growth Hormone, and Triiodothyronine
Authors: Swenne Ingemar 
Published: September 2013

DNA replication and insulin release have been studied in islets isolated, using a tissue culture technique, from rat fetuses of different gestational ages. The islets were cultured for 3 days in media with high and low concentrations of glucose or amino acids. The DNA replication was determined by autoradiography and the insulin secreted into the medium was measured by radioimmunoassay. In islets of 22-day-old fetuses, DNA replication was stimulated by both glucose and amino acids. At gestational days 18 and 20, only amino acids increased DNA replication. However, both high glucose and high amino acid concentrations increased the islet insulin secretion into the culture medium at all ages studied.
In an attempt to induce glucose-sensitive DNA replication in vitro, islets obtained from 18- and 20-day-old fetal pancreata were cultured in the presence of either triiodothyronine or human growth hormone. Triiodothyronine failed to influence either DNA replication or insulin release. Growth hormone, however, increased DNA replication and insulin release in both the experimental groups but did not induce a growth response to glucose.
It is concluded that the appearance of glucose-stimulated B-cell growth is a late event in the fetal development of the rat, parallelling the late maturation of both insulin biosynthesis and release. This finding may explain the difficulties in producing islet cell hyperplasia and diabetic fetopathy previously shown in rat models of diabetes in pregnancy.
Fibrinopeptide-A in Diabetes Mellitus: Relation to Levels of Blood Glucose, Fibrinogen Disappearance, and Hemodynamic Changes
Authors: Jones Robert L 
Published: September 2013

Plasma and urine fibrinopeptide-A (FPA) levels were investigated in type I and II diabetic patients. Plasma FPA and 24-h urinary excretion of FPA were significantly elevated in diabetic patients compared with normal volunteers, indicating augmented thrombin activity in diabetes. Plasma and urine FPA did not differ between type I and type II diabetic subjects. Comparison ofplasma FPA with blood glucose and hemoglobin A1 (HbA,) indicated that elevation of FPAis rapidly reversible and intermittent during hypo- and hyperglycemia. Although elevated plasma FPA was seen in patients of short as well as long duration of diabetes, plasma and urine FPA correlated with duration of diabetes in type I patients.
In type I diabetic patients with vascular complications, hyperglycemia induced by an oral glucose challenge was accompanied by elevation of plasma FPA and acceleration of fibrinogen disappearance. These responses were not seen when the patients were treated with intravenous (i.v.) heparin before the glucose challenge. In patients without vascular complications, there was also an acceleration of fibrinogen disappearance and a marginal (not statistically significant) elevation of plasma FPA seen after the FPA response observed in vascular disease patients. In all patients, induced hyperglycemia resulted in a decrease in hematocrit and hemoglobin (blood volume expansion) and an increase in pulse pressure indicating hemodynamic changes. The association of hyperglycemia and hemodynamic changes with augmented thrombin activity is consistent with a mechanism for fibrin formation and deposition based on endothelial injury and/or increased vascular permeability. Fibrin deposition due to such a mechanism may participate in the development of the vascular complications of diabetes.
Pathogenesis and Prevention of the Dawn Phenomenon in Diabetic Patients Treated with CSII
Authors: Koivisto Veikko A , Yki-Järvinen Hannele , Helve Eero , Karonen Sirkka-Liisa , Pelkonen Risto 
Published: September 2013

The mechanism of the dawn phenomenon was studied in 12 C-peptide-negative type I diabetic patients (age 30 ± 2 yr) treated with continuous subcutaneous insulin infusion. During constant basal infusion, nocturnal glycemia remained constant until 4 a.m., but began to rise thereafter in 10/12 patients, with the mean rise from 4.6 ± 0.4 mmol/L to 6.1 ± 0.7 mmol/L (P &lt; 0.01) by 8 a.m. In these patients the rate of glucose production (Ra, 2.14 ± 0.04 mg/kg/min, 3-H3-glucose infusion) exceeded the rate of utilization (Rd, 1.89 ± 0.03 mg/kg/ min, P &lt; 0.02). When the patients were restudied after the infusion rate was increased by 49 ± 7%, Ra fell to 1.75 ± 0.03 mg/kg/min (P &lt; 0.01) and the dawn phenomenon was abolished. However, both Ra and Rd remained higher in the diabetic subjects (P / 0.05) than in eight healthy control subjects, in whom Ra (1.66 ± 0.02 mg/kg/min) was equal to Rd with glycemia remaining unchanged. Peripheral free insulin levels in the diabetic patients were similar during constant (12.3 ± 0.5 mU/L) and increased infusion rate (11.3 ± 0.4 mU/L), and higher than those of the control subjects (5.2 ± 0.2 mU/L, P &lt; 0.05). A diurnal rise in serum cortisol levels occurred 1 h earlier in the diabetic than in the control subjects, and Ra was directly proportional to serum cortisol concentration (r = 0.61; P &lt; 0.01). Serum growth hormone levels were also slightly higher in the diabetic than the control subjects.
In conclusion: (1) A dawn phenomenon is associated with an excessive rate of glucose production, rather than impaired utilization; (2) this may be explained, at least in part, by elevated counterregulatory hormone levels; and (3) a step-up in the overnight insulin delivery reduces hepatic glucose production and so prevents the dawn phenomenon.
Comparative Studies on Insulin-Like Growth Factor II and Insulin Processing by Vascular Endothelial Cells
Authors: Hachiya H L , Carpentier J -L , King G L 
Published: September 2013

Processing of circulating polypeptide hormones by vascular endothelial cells may be critical to hormone transport from the vascular lumen to tissue sites of action. The comparative processing of insulin-like growth factor II (IGF II) and insulin by cultured bovine aortic endothelial cells was examined. These cells possess high-affinity receptors for IGF II and insulin, as shown by competitive-binding studies. At 37°C, internalization determined by both resistance to an acid wash and electron microscopy was rapid with 50–70% of bound IGF II and insulin internalized at 60 min. Subsequently, between 70 and 75% of the internalized hormones were released from the cells within 60 min.
Although most of both hormones were released intact, degradation of IGF II was greater than that of insulin by two- to threefold, as assessed by G-50 chromatography and trichloroacetic acid precipitability. Leupeptin, a specific lysosomal protease inhibitor, increased cell-associated 125I-labeled IGF II by 53.0 ± 6.0% and decreased degradation by 55%; however, it was without effect on 125I-labeled insulin. Chloroquine and monensin, which act at the lysosomes and at other sites, increased both cell-associated IGF II and insulin and decreased the degradation of both hormones. The increases in cell-associated 125I—IGF II produced by chloroquine (42.0 ± 7.4%) and monensin (78.3 ± 8.5%) were quantitatively similar to the decreases in IGF II degradation caused by the agents; however, the increase in cell-associated insulin was approximately threefold greater than could be accounted for simply by decreased insulin degradation.
These results demonstrate two functional pathways for the processing of internalized hormones in the endothelial cell: a lysosome-targeted degradative pathway and a nonlysosomal pathway that may mediate the release of primarily intact hormone from the cells. IGF II processing and insulin processing by endothelial cells are different, due in part to greater channeling of IGF II, compared with insulin, into the degradative pathway. The capacity of endothelial cells to differentially process polypeptide hormones represents a potential mechanism that may modulate hormone delivery to tissue Sites Of action.
Insulin Sensitivity and Exogenous Insulin Clearance in Graves' Disease: Measurement by the Glucose Clamp Technique and Continuous Indirect Calorimetry
Authors: Randin Jean-Pierre , Tappy Luc , Scazziga Bianca , Jequier Eric , Felber Jean-Pierre 
Published: September 2013

Insulin sensitivity was measured in a group of seven thyrotoxic patients and in a group of seven normal subjects by means of the glucose clamp technique. Infusion of insulin at a rate of 0.80 ± 0.05 mU/kg · min in the hyperthyroid patients and of 0.55 ± 0.04 mU/kg · min in the control group was performed to obtain a steady-state plasma insulin concentration of approximately 50 μU/ml. Substrate oxidation rates were measured in the postabsorptive state and during the 2 h of the clamp by means of continuous indirect calorimetry.
In the postabsorptive state, hyperthyroid patients presented a preferential oxidation of lipids. During the period 60–120 min of the clamp, mean plasma glucose (92 ± 2 versus 93 ± 2 mg/dl), insulin (50 ± 5 versus 58 ± 3 μU/ml), and total glucose metabolism (5.8 ± 0.7 versus 6.1 ± 0.3 mg/kg - min) were similar in the hyperthyroid patients and the control subjects. The rate of glucose oxidation was higher in hyperthyroid patients than in control subjects (4.3 ± 0.5 versus 2.2 ± 0.2 mg/kg min, P &lt; 0.001), while that of lipid oxidation was similar in both groups (0.6 ± 0.2 versus control 0.7 ± 0.1 mg/kg - min). The calculated metabolic clearance rate of insulin was markedly higher in the hyperthyroid patients (1144 ± 132 ml/min) than in the normal subjects (812 ± 56 mi/min, P &lt; 0.025).
It is concluded that insulin sensitivity is not altered in the thyrotoxic state. The major route of insulin-stimulated glucose disposal in the hyperthyroid patients appears to be glucose oxidation.
Insulin Induces Progressive Insulin Resistance in Cultured Rat Adipocytes: Sequential Effects at Receptor and Multiple Postreceptor Sites
Authors: Garvey W Timothy , Olefsky Jerrold M , Marshall Stephen 
Published: September 2013

We have examined the ability of insulin to regulate insulin action in primary cultured adipocytes, and found that insulin induces progressive insulin resistance in this target tissue. To assess effects at both receptor and postreceptor sites, we cultured cells in the absence (control) and presence of 100 ng/ml insulin, and, after various times, measured the dose response of insulin's ability to bind cell-surface receptors and stimulate 2-deoxyglucose transport. In control cells, insulin binding (0.2 ng/ml) was increased 10–13% due to an apparent increase in receptor affinity (6–24 h). A comparable increase in affinity was also observed in treated cells; however, concomitantly, insulin decreased the number of cell-surface receptors causing a slowly progressive net decrease in binding after a 6– 10-h lag (maximal 30% at 24 h). When insulin action was assessed in control cells, the functional consequence of increased receptor binding was hypersensitization (i.e., increased insulin sensitivity) manifested by a leftward shift in the 2-deoxyglucose dose-response curve. On the other hand, in the treated cells, insulin produced insulin resistance initially by decreasing insulin sensitivity. The ED50 for insulin stimulation of glucose transport increased 84% from 0.31 to 0.57 ng/ml at 6 h without a net change in insulin binding; this was the result of a decrease in coupling efficiency between occupied receptors and the insulin effect. Receptor uncoupling progressively increased in severity, but before the full effect was reached insulin also caused a rapid decline in maximally stimulated glucose transport rates (between 6 and 10 h). This decrease in insulin responsiveness (maximal 52%) exacerbated overall insulin resistance, and was indicative of a postreceptor defect in the glucose transport system. Finally, insulin-induced receptor downregulation contributed, along with uncoupling, to a further decrease in insulin sensitivity, and constituted a more long-term regulatory mechanism. We also observed that insulin could regulate the basal glucose transport system by preventing a progressive rise in basal transport observed in control cells.
In conclusion, primary cultured adipocytes can be used to study long-term regulation of insulin action. We found that insulin induces progressive insulin resistance with sequential effects at multiple sites in the insulin action pathway, including decreased coupling efficiency between occupied receptors and stimulated glucose transport, a postreceptor defect in insulin responsiveness of the glucose transport system, and receptor downregulation. These mechanisms may be relevant to the cellular defects in insulin action present in clinical states of insulin resistance and hyperinsulinemia.
Aldehyde Dehydrogenase Activity and Large Vessel Disease in Diabetes Mellitus: A Preliminary Study
Authors: Jerntorp Peter , Öhlin Hans , Almér Lars-Olof 
Published: September 2013

Type II diabetic subjects, 26 with symptoms and/or signs of large vessel disease (LVD group) and 26 free from clinical vascular disease (FVD group), matched for sex, age, body weight, and duration of diabetes after diagnosis, together with 28 healthy controls participated in a preliminary study on new potential risk factors of large vessel disease.
The activity of erythrocyte aldehyde dehydrogenase (ALDH) was significantly higher (P &lt; 0.005) in the LVD than in the FVD group and in the controls, as indicated by a shorter half-life of acetaldehyde in homogenates of erythrocytes and plasma (100 ± 11, 203 ± 28, and 180 ± 21 min, respectively). The results were unaffected by antidiabetes therapy, blood glucose control, alcohol consumption, or by recognized risk factors of angiopathy, such as blood pressure, hyperlipidemia, or smoking. Whether ALDH activity is a primary factor in large vessel disease or is merely a secondary phenomenon is unknown. However, ALDH activity is a critical factor determining chlorpropamide alcohol flush (CPAF), which has been suggested to be an inherited trait in some type II diabetic subjects.
In conclusion, high ALDH activity was shown to be associated with an increased risk of large vessel disease in diabetes.
Transfer of Autoimmune Diabetes Mellitus with Splenocytes from Nonobese Diabetic (NOD) Mice
Authors: Wicker Linda S , Miller Beverly J , Mullen Yoko 
Published: September 2013

The nonobese diabetic (NOD) mouse, a model of human type I diabetes, develops insulitis beginning at 4–6 wk of age. By 30 wk of age, 72% of females and 39% of males develop spontaneous diabetes, apparently because of an overwhelming autoimmune response to the insulin-producing β-cells within the islets. To identify the immune mechanism responsible for destruction of β-cells in the NOD mouse, we developed an adoptive transfer protocol that induces diabetes in NOD mice at an age when spontaneous diabetes is rarely observed.
Splenocytes from overtly diabetic NOD mice were unable to transfer diabetes to very young (≤6 wk) irradiated NOD mice but effectively transferred diabetes to irradiated NOD mice 6 wk of age. In such transfers, overt diabetes was induced within 12–22 days in &gt;95% (79/82) of the recipients. Thus, transfer of splenocytes to young mice induces them to become diabetic at a higher frequency and at a younger age than their untreated littermates. Equally successful transfers with as few as 5 × 106 spleen cells have been performed in male and female NOD mice, even though males display a lower spontaneous incidence of diabetes than females. Splenocytes obtained from diabetic mice maintained on insulin for up to 2 mo also transferred diabetes.
Because NOD mice display increasing levels of insulitis with age, spleen cells obtained from nondiabetic NOD mice of different ages were tested for their ability to transfer diabetes. Spleen cells obtained from 7-wk-old nondiabetic donors were unable to transfer disease, suggesting that high numbers of effector cells are not yet present in the spleens of young NOD mice. In contrast, spleen cells obtained from most nondiabetic NOD mice &gt;15 wk of age were able to transfer diabetes, indicating that the donor need not be overtly diabetic at the time of transfer.
Our study provides direct demonstration of the immunological nature of the diabetic disease process in the NOD mouse and provides a method to determine which cells are the effectors of β-cell destruction.
Development of a Predictive Model for Symptomatic Neuropathy in Diabetes
Authors: Weinberg C R , Pfeifer M A 
Published: September 2013

In evaluating therapeutic interventions aimed at preventing diabetic neuropathy, choosing a suitable measure of neural function is difficult, partly because the relation between most available objective measures and the development of symptomatic neuropathy (SN) is unclear. Using data from 67 diabetic patients, we developed a linear logistic regression model to assess the relationship between SN and a set of neural measures, including dark-adapted pupil size; pupillary latency; heart rate; a measure of respiratory sinus arrhythmia (); the Valsalva ratio; and conduction velocities for the peroneal, median motor, and median sensory nerves. Models allowed for possible effects related to age, sex, duration and type of diabetes, glyco-sylated hemoglobin, and adiposity. Thirty-two of the patients reported SN (autonomie and/or sensorimotor). The best-fitting model for predicting the presence of any SN included only heart rate, duration of disease, and . Exclusion of duration (P &lt; .01), or heart rate (P &lt; .05), or (P &lt; .001) significantly impaired the fit of the model.
To evaluate the temporally predictive power of the model, nine of the asymptomatic patients were reinter-viewed 2 yr later by the same interviewer, who was unaware of the results of the modeling. Four of five to whom the model had assigned high probability of symptoms had indeed developed SN during the follow-up period, whereas none of the four assigned low probability had developed SN (P &lt; .05). Thus it seems that a measure of respiratory sinus arrhythmia provides an index of neural function strongly related to SN, and our follow-up data suggest that diminished can be used to predict the development of SN in diabetes.