bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary and Renal Tissue Kallikrein in the Streptozocin-diabetic Rat
Authors: Mayfield Ronald K , Margolius Harry S , Bailey Graham S , Miller Donald H , Sens Donald A , Squires Josephine , Namm Donald H 
Published: September 2013

The renal kallikrein-kinin system is thought to participate in blood pressure regulation and displays abnormalities in human hypertension, as well as in many animal models of hypertension. Urinary excretion and tissue levels of renal kallikrein were measured in streptozocin (STZ)-diabetic rats in relation to blood pressure, glycemia, and insulin treatment.
In study 1, STZ-diabetic rats with marked hyperglycemia showed reduced kallikrein-like esterase excretion, compared with control rats, when first measured after 7 days of diabetes (9.9 ± 2.5 versus 17.5 ± 2.4 EU/24 h, P &lt; 0.05). This difference increased with time and, after 210 days, urinary esterase excretion in diabetic and control rats was 6.7 ± 2.1 and 39.0 ± 6.0 EU/24 h, respectively (P &lt; 0.001). Urine kallikrein, measured by radioimmunoassay, was similarly reduced in diabetic rats (40.4 ± 8.0 versus 88.0 ± 6.5 μg/24 h, at 30 days, P &lt; 0.001). At 120 days, systolic blood pressures were elevated in diabetic rats (P &lt; 0.05), and at 180 days over 60% of the diabetic rats had pressures above the highest pressures of control rats.
In study 2, STZ-diabetic rats were treated with insulin for 2 wk (2 U NPH at 0800 h, or 2 U NPH at 0800 and 1600 h). In the single-dose group, with hyperglycemia similar to that of diabetic rats in study 1, kallikrein excretion was reduced as early as day 2, compared with nondiabetic rats (56.0 ± 6.1 versus 109 ± 9.4 μg/24 h, respectively, P &lt; 0.001). In the diabetic rats treated with twice-daily insulin, glycemia was reduced and daily urine glucose was not significantly different from that in controls. Kallikrein excretion was normal in these rats.
In study 3, we measured renal tissue kallikrein i untreated and insulin-treated (2.25 U PZI) STZdiabetic rats. After 2 wk, untreated diabetic rats had decreased renal kallikrein compared with nondiabetic rats (22.8 ± 1.6 versus 29.7 ± 1.4 ng/mg protein, P &lt; 0.001). In the insulin-treated diabetic rats with near-normal plasma glucose levels, renal kallikrein (35.8 ± 2.1 ng/mg protein) was increased above that of untreated diabetic (P &lt; 0.001) or nondiabetic rats (P &lt; 0.05).
These studies confirm that STZ-diabetic rats develop systolic hypertension as assessed by tail cuff measurement. There is an early reduction in kallikrein excretion, which reflects reduced renal enzyme content. These abnormalities in kallikrein can be prevented by insulin treatment. Relationships of these changes in urinary and renal kallikrein to the function of the diabetic kidney and development of hypertension in this model can now be explored.
The Nature of Insulin Secretory Defect in Aging Rats
Authors: Draznin Boris , Steinberg Jay P , Wayne J , Sussman Karl E 
Published: September 2013

We have attempted to define the nature of insulin secretory defect(s) in aged animals. In these studies, pancreatic islets were isolated from 2- and 18-mo-old Fischer 344 rats. Margination of secretion vesicles during exocytosis was assessed by measuring the recruitment of somatostatin (SRIF) receptors to the surface membrane. Section vesicle lysis was studied by measuring insulin release into the incubation media.
Submaximal and maximal glucose-induced insulin secretion was significantly greater in islets isolated from younger rats (P &lt; 0.01). SRIF recePtor recruitment was stimulated by glucosein both younger and older Fischer 344 rats. However, an increase in SRIF receptor recruitment wasreduced in islets isolated from older animals (from 2.14 ± 0.4 to 4.6 ± 0.4 fmol/10 islets) (P &lt; 0.01) as compared with islets from younger animals (from 2.6 ± 0.2 to 6.2 ± 0.4 fmol/10 islets). When secretion vesicle lysis was inhibited by the presence of sodium isethionate in the incubation media, glucose (300 mg/dl) failed to stimulate secretion vesicle margination to the plasma membrane. In contrast, glyburide (0.6 μg/ml) continued to stimulate directly secretion vesicle margination in islets from aged animals (from 2.1 ± 0.3 to 6.0 ± 0.3 fmol/10 islets).
We conclude that glucose-induced margination of secretion vesicles at the plasma membrane is impaired by the aging process. This impairment results in lower submaximal and maximal insulin secretory response to glucose. The fact that glyburide is capable of stimulating secretion vesicle margination suggests that glucose signal recognition and/or stimulus-secretion coupling may be the locus of impairment in the process of insulin secretion in older animals.
Beta-Endorphin Modulation of the Glucoregulatory Effects of Repeated Epinephrine Infusion in Normal Dogs
Authors: El-Tayeb K M A , Brubaker P L , Vranic M , Lickley H L A 
Published: September 2013

Successive epinephrine infusions were used as a partial model to examine hormonal and metabolic responses to repeated stress stimuli. As both the endogenous opiates and epinephrine are released in response to stress, we have also studied interactions between epinephrine and B-endorphin. Epinephrine (0.1 μg/kg · min) was infused for 60 min, followed by a 60-min recovery, a second 60 min of epinephrine, and a 60-min recovery, in nine normal, conscious dogs. In a similar study, B-endorphin (0.06 μg/kg · min) was given 30 min before epinephrine, then continuously infused throughout the study (N = 4 dogs). When epinephrine was infused, levels rose to 600–800 pg/ml. The changes in glucagon, B-endorphin, FFA, and hepatic glucose production were similar during both epinephrine infusions, but there was a diminished insulin response, a greater decrease in glucose metabolic clearance, and a greater increase in plasma glucose with the second epinephrine infusion. When B-endorphin was given, plasma levels increased to 5.3 ng/ml. Compared with the infusion of epinephrine alone, there was a much greater rise in plasma glucose due to greater suppression of glucose metabolic clearance. With the second epinephrine infusion, however, the changes in glucose concentration were not substantially different from those seen during the second infusion of epinephrine alone, as both hepatic glucose production and glucose metabolic clearance were suppressed. B-endorphin diminished the insulin and glucagon responses during the first epinephrine infusion and abolished them during the second, but did not alter the FFA, ACTH, or cortisol responses to epinephrine.
Thus, (1) successive epinephrine infusions appear to desensitize the B-cells, resulting in a greater hypergly-cemic response due to exaggerated suppression of MCR, and (2) B-endorphin (0.06 jig/kg min) attenuated epinephrine's effects on the pancreatic A- and B-cells, and enhanced epinephrine's hyperglycemic effects by potentiating its inhibitory effect on MCR and modulating its stimulatory effects on the liver, through direct and/or indirect mechanisms.
The Effect of Metabolic Control on Hemodynamics in Short-Term Insulin-dependent Diabetic Patients
Authors: Mathiesen E R , Hilsted J , Feldt-Rasmussen B , Bonde-Petersen F , Christensen N J , Parving H -H 
Published: September 2013

Hemodynamics variables (heart rate, arterial blood pressure, cardiac output, hepato-splanchnic blood flow, forearm blood flow, and plasma catecholamines) were measured during good (median blood glucose 4.7 mmol/L) and poor (median blood glucose 16.3 mmol/L) metabolic control in eight young, short-term, insulindependent diabetic patients. The measurements were performed twice within 2 wk, in random order. Continuous subcutaneous insulin infusion (CSII) was applied for 1 wk in order to obtain good control. All eight patients had elevated cardiac output (median 9%) and forearm blood flow (median 34%) during poor compared with good metabolic control, P &lt; 0.01. In contrast, hepato-splanchnic blood flow was lower (median 12%) during poor compared with good metabolic control, P &lt; 0.05. Heart rate remained unchanged, while mean arterial blood pressure was slightly higher during poor control, P &lt; 0.05. Five of six patients had elevated plasma noradrenaline concentration during poor metabolic control. Due to the small number of patients investigated, no valid conclusion regarding the activity of the sympathoadrenal system can be drawn.
Our study suggests that both increased cardiac output and reduced hepato-splanchnic blood flow (redistribution) contribute to the elevated blood flow previously demonstrated in various other organs and tissues in diabetic patients during poor metabolic control.
Influence of Growth Hormone on Overnight Insulin Requirements in Insulin-dependent Diabetes
Authors: Skor Donald A , White Neil H , Thomas Lorraine , Santiago Julio V 
Published: September 2013

After a 0100–0300 h nadir, the insulin requirements to maintain blood glucose at 90–110 mg/dl increase substantially in the prebreakfast (0600–0800 h) period in some insulin-dependent diabetic patients (IDDMs). Early insulin-like and delayed insulin-antagonistic effects of physiologic early morning increases in growth hormone (hGH) secretion may account for this variability of overnight insulin requirements. To assess the role of hGH, we studied five IDDMs using a closed-loop insulin infusion device (Biostator, GCIIS). Either saline (C) or somatostatin plus glucagon (SRIF + G) was infused during separate overnight (2400–0800 h) study periods. An infusion of hGH from 2400 to 0130 h was added to SRIF + G infusion during an additional study period (SRIF + G + hGH). In comparison to 0100–0300 h, mean insulin infusion rates required to maintain blood glucose values between 105 and 120 mg/dl during the prebreakfast period increased by 66 ± 25% during C, and 42 ± 12% during SRIF + G when serum growth hormone was suppressed to &lt;0.75 ng/ml. During SRIF + G + hGH, the mean prebreakfast insulin infusion rate increased by 42 ± 11% with a mean peak hGH level of 14.7 ± 5.4 ng/ml at 0130 h. Mean plasma free insulin levels remained constant during the night despite the significantly higher insulin infusion rates between 0600 and 0800 h.
During SRIF + G, insulin requirements remained constant overnight before 0600 h, whereas during both C and SRIF +G + hGH conditions, a nadir was noted between 0100 and 0300 h. Data pooled from 10 overnight, saline infusion studies suggest that the early morning nadir in insulin requirements occurs within 60 min of the peak hGH concentration. We conclude that the physiologic early morning increase in hGH is not an essential component of the prebreakfast increase in insulin requirements. Nocturnal growth hormone secretion may, however, contribute to the early morning nadir in insulin requirements seen in IDDM.
Screening of High-Risk and General Populations for Gestational Diabetes: Clinical Application and Cost Analysis
Authors: Lavin Justin P 
Published: September 2013

Two thousand seventy-seven women attending a university-based prenatal clinic were screened for gestational diabetes. The patients were divided into two groups. Group 1 consisted of 959 patients with historic or clinical factors traditionally employed to identify patients as being at high risk for the occurrence of gestational diabetes. Group 2 consisted of the remaining 1118 patients. The O'Sullivan 50-g 1-h test, with an upper limit of normal for serum glucose of 150 mg/dl, was employed as the initial screening procedure. Patients with an abnormal screening test underwent a 3-h oral glucose tolerance test (GTT) with a 100-g load. The values recommended by the First American Diabetes Association Workshop-Conference on Gestational Diabetes were employed for interpretation. Group 1 patients underwent screening at their initial visit and again at 28 wk gestation. Group 2 patients underwent an identical screening sequence between 28 and 32 wk gestation. Cost analysis was performed.
The prevalences of positive screening tests were 7.2% and 6.1%, and the frequencies of abnormal GTTs were 1.5% and 1.4% among group 1 and group 2 patients, respectively. These rates were not statistically significantly different. Overall, 46.7% and 53.5% of the cases of gestational diabetes were identified among the patients with and without risk factors, respectively. The total cost of the screening program was $9869.00. The cost per patient screened and the cost per case of gestational diabetes identified were $4.75 and $328.96, respectively. These results reemphasize the inadequacy of screening only those patients with traditional risk factors for gestational diabetes and demonstrate the feasibility of implementing a program of universal glucose screening among, a large obstetric population. The observed cost compares favorably with screening tests employed for other diseases during pregnancy.
Relationship Between Maternal and Fetal Fuels and Placental Glucose Transfer in Rats with Maternal Diabetes of Varying Severity
Authors: Herrera Emilio , Palacin Manuel , Martin Antonia , Lasuncion Miguel Angel 
Published: September 2013

Gestational diabetes mellitus (GDM) is a nonhomogenous entity known to affect fetal development in different ways in both rats and human beings. The degree of severity of diabetes could affect the maternal-fetal transfer of metabolic fuels and consequently influence fetal development. To study this hypothesis, pregnant rats were made diabetic by streptozocin (STZ) treatment (45 mg/kg) at day 7 of gestation and were treated with different daily doses of insulin until the 20th day of gestation, when-they were killed and examined. Differences in plasma glucose levels in the groups studied were not accompanied by differences in plasma glycerol, β-hydroxybutyrate (β-OHB), or total amino acid levels in mothers or their fetuses. Fetal/maternal ratios of these circulating fuels were not modified by maternal diabetes, whereas the glucose level was enhanced in diabetic rats not treated with insulin. Placental glucose transfer was studied directly with a recently reported in situ experimental design and was found to increase linearly with maternal glycemia, independently of whether this was modified by insulin treatment or by acute intravenous (i.v.) infusion of glucose in normal animals. Lactate production by the fetal/placental unit decreased in proportion to the glucose level in the maternal circulation.
The present data indicate that the diabetic condition of the mother rat does not modify the mechanisms of placental transfer of metabolic fuels to the fetus, and that the actual transfer is mainly dependent on the concentrations of these fuels in the maternal circulation. The limited capacity of the fetus to handle the great influx of glucose through the placenta of a highly hyperglycemic mother may aggravate the diabetic condition of the fetus, affecting its subsequent development.
Gestational Diabetes Mellitus: Is Further Improvement Necessary?
Authors: Philipson Elliot H , Kalhan Satish C , Rosen Mortimer G , Edelberg Stuart C , Williams Thomas G , Riha Margo M 
Published: September 2013

The maternal antepartum, intrapartum, and neonatal characteristics of 158 patients with gestational diabetes mellitus (GDM) attending a large teaching hospital between 1979 and 1983 were described and compared with a matched nondiabetic control group. The primary cesarean section rate in patients with GDM (18%) was significantly greater than in the control group (11%, P &lt; 0.04). Neonatal macrosomia, as reflected in mean birthweight (P &lt; 0.04), the number of neonates weighing &gt; 4 kg (P &lt; 0.05) and large-for-gestationalage infants (P &lt; 0.05), and the birthweight adjusted for gestational age (K-score, P &lt; 0.01) was significantly increased in the diabetic group.
The characteristics of patients with GDM treated with diet alone and diet and insulin together were examined. The insulin-therapy group was characterized by more patients older than 25 yr (P &lt; 0.01) and a higher mean birthweight (3743 ± 677 g) (P &lt; 0.02) than the dietalone group. This may reflect an increased magnitude of glucose intolerance in the insulin-treated group. Obese patients with GDM delivered heavier neonates than the nonobese patients with GDM (P &lt; 0.01). Although there was no difference between the groups, perinatal mortality was present in this study. These data indicate that the major perinatal morbidity in GDM included increased cesarean section for fetal macrosomia. Early diagnosis with strict diagnostic criteria and rigid antenatal surveillance may result in further improvements in outcome.
Hormonal Responses to Exercise in Diabetic and Nondiabetic Pregnant Patients
Authors: Artal Raul , Wiswell Robert , Romem Yitzhak 
Published: September 2013

The hormonal responses to low-level exercise in pregnancy have been studied in 13 insulin-requiring diabetic patients and 42 control subjects.
We found no significant changes in plasma glucose, epinephrine, glucagon, or FFA with this level of exercise in the study group and control subjects; but plasma norepinephrine showed a significant increase with exercise.
This type of exercise appears to be safe and could serve as a model for exercise prescription for attaining improved glucose tolerance in pregnant diabetic women.
Autoantibodies Against the Insulin Receptor: Dissociation of the Acute Effects of the Antibodies from the Desensitization Seen with Prolonged Exposure
Authors: Grunfeld Carl , Jones Debra S , Shigenaga Judy K 
Published: September 2013

The effect of antibodies against the insulin receptor (anti-R) found in a patient with the type B syndrome of insulin resistance and acanthosis nigricans was characterized using 3T3-L1 cultured fat cells. Anti-R acutely mimicked the action of insulin by stimulating deoxyglucose uptake. With more prolonged exposure, this insulinomimetic effect decayed, glucose metabolism returned to basal levels, and the cells became severely resistant to the actions of insulin. As seen with anti-R from a previous patient, desensitization consisted of both a dramatic decrease in the maximal responsiveness of the cells to insulin and a shift in the dose-response curve for insulin-stimulated glucose oxidation.
The acute and chronic effects of anti-R were then compared. The concentration of anti-R required to halfmaximally inhibit insulin binding averaged more than twice that required for half-maximal stimulation of deoxyglucose uptake, consistent with the amount of spare receptors in 3T3-L1 cells. After prolonged exposure, the insulinomimetic activity was completely lost at all concentrations of anti-R, even at those that did not completely induce insulin resistance. Thus, loss of the insulinomimetic activity of anti-R is necessary, but not sufficient, to cause desensitization. Less anti-R was required to desensitize cells to insulin than would have been predicted on the basis of the acute inhibition of binding and the number of spare receptors. In addition, the amount of anti-R required to half-maximally inhibit insulin binding after prolonged exposure was an order of magnitude less than that during acute exposure, implying a progressive loss of insulin receptor binding during antibody-induced desensitization. When cells were treated with subsaturating concentrations of anti-R, insulin binding decreased over a period of several hours.
Finally, an acid wash (capable of dissociating antigen-antibody complexes) could not restore insulin binding after desensitization, but could restore insulin binding if cells were exposed to anti-R at 4°C. These results support the theory that insulin receptors are removed from the cell surface during antibody-induced desensitization.
An Ascochlorin Derivative, AS-6, Reduces Insulin Resistance in the Genetically Obese Diabetic Mouse, db/db
Authors: Hosokawa Tomoyoshi , Ando Kunio , Tamura Gakuzo 
Published: September 2013

An ascochlorin derivative, AS-6, is a new hypoglycemic agent orally active in both obese hyperinsulineroic and insulin-deficient diabetic animal models. AS-6, when given as a 0.025–0.2% admixture in the diet, dose-dependently ameliorated polydipsia, polyuria, and glycosuria in the genetically obese diabetic mouse, C57BL/KsJ db/db, while neither insulin nor tolbutamide showed any beneficial effects. The amelioration by AS-6 was associated with a marked decrease in serum glucose and triglyceride. The effects persisted at least 10 wk, accompanied by a steady decrease in drinking water consumption. The chronic treatment prevented pancreatic islet degeneration, e.g., degranulation of the β-cells, basophilic appearance of the exocrine border around the islets, and small round cell infiltration. The isolated islets from AS-6-treated mice released much more insulin in response to glucose than those from untreated controls. A significant correlation between serum immunoreactive insulin and glucose/triglyceride from both treated and untreated mice suggests that AS-6 restores sensitivity and responsiveness to insulin to the mice.
In fact, the combined treatment with insulin synergistically decreased serum glucose by 50% below AS-6 treatment alone. Furthermore, the epididymal fat pad slices from AS-6-treated db/db mice increased CO2 generation and lipogenesis over the untreated controls, and the glucose metabolic rate (CO2 generation plus lipogenesis from U-[14C]-glucose) in the slices and the serum glucose level inversely correlated at r = 0.8799. These facts indicate that AS-6 reduces insulin resistance in db/db mice.