bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geographic, Ethnic, and Racial Variations in the Incidence of Gestational Diabetes Mellitus
Authors: Hadden D R 
Published: September 2013

The prevalence of diabetes and of gestational diabetes varies considerably between countries and within countries. There are also major national and international differences in the important end points of fetal or neonatal death and congenital fetal abnormality. These differences relate to multiple factors, of which diabetes or gestational diabetes represents only a part of the total pathologic effect.
There is also international disagreement on the most appropriate diagnostic criteria for gestational diabetes. The main uncertainty is whether to adopt the World Health Organization figures, e.g., venous plasma glucose 2 h after 75 g glucose ≥ 140 mg/dl (8.0 mmol/L) as gestational impaired glucose tolerance, and ≥200 mg/dl (11.0 mmol/L) as gestational diabetes, or to use the Boston figures, e.g., venous plasma glucose 2 h after 100 g glucose ≥ 165 mg/dl (9.5 mmol/L) as gestational diabetes. It is hoped that standards for pathologic hyperglycemia in pregnancy can be agreed on for use in all countries for all populations.
Effect of E-Series Prostaglandins on Cyclic AMP-dependent and -independent Hormone-stimulated Glycogenolysis in Hepatocytes
Authors: Brass Eric P , Garrity Maureen J 
Published: September 2013

The effect of E-series prostaglandins (PGE) on hormone-stimulated glycogenolysis was studied in isolated rat hepatocytes. As previously reported, the physiologically active analogue 16,16-dimethyl-PGE2 inhibited glucagon-stimulated glycogenolysis. This effect could be reproduced by repetitive addition of PGE2 to compensate for PGE2 catabolism. In contrast, glycogenolysis stimulated by N6,O2′-dibutyryladenosine-3/5′-cyclic monophosphate (dibutyryl-cAMP) was unaffected by either PGE2 or 16,16-dimethyl-PGE2 (rate of glycogenolysis with 0.34 μM dibutyryl-cAMP plus 1.7 (μM 16,16-dimethyl-PGE2 = 99 ± 6% of rate with 0.34 μM dibutyryl-cAMP alone; mean ± SEM, N = 5). Similarly, glycogenolysis stimulated by 8-bromoadenosine-3′,5′-cyclic monophosphate was not inhibited by PGE2 or 16,16-dimethyl-PGE2.
Epinephrine-stimulated glycogenolysis was inhibited by 16,16-dimethyl-PGE2 in a dose-dependent manner. PGE inhibited the cAMP-independent stimulation of glycogenolysis resulting from phenylephrine or angiotensin II exposure (rate of glycogenolysis with 8 μM phenylephrine + 1.7 μM 16,16-dimethyl-PGE2 = 65 ± 10% of rate with 8 μM phenylephrine alone, N = 4, P &lt; 0.05; 4.9 μM angiotensin 11 + 1.7 μM 16,16-dimethyl-PGE2 = 75 ± 7% of rate with 4.9 μM angiotensin II alone, N = 4, P &lt; 0.05). Glycogenolysis stimulated by the calcium ionophore A23187 was also inhibited by PGE (rate of glycogenolysis with 0.55 μg/mlA23187 + 1.7μM16,16-dimethyl-PGE2 = 83 ± 5% of rate with 0.55 μg/ml A23187 alone, N = 7, P &lt; 0.05).
Thus, PGE can inhibit both cAMP-dependent and cAMP-independent hormone-stimulated glycogenolysis. The results suggest two sites of inhibition, one consistent with inhibition of adenylate cyclase stimulation and a second inhibiting calcium-mediated stimulation at an undefined site.
Assessment of Fluorescein Angiograms
Authors: Kohner E M , Lawson P M , Ghosh G , Testa M ,   The Kroc Collaborative Study Group
Published: September 2013

Quantitation of the earliest changes in abnormal retinal morphology using fluorescein angiography is potentially superior to retinal photography. However, the critical importance of flawless technique, limitations in the size of the field available for detailed study, and observer variability constitute major disadvantages. A protocol describing standards of photography and of injection was developed. Methodology for counting microaneurysms (Ma) was developed at a central laboratory and applied in suitable photographs obtained at 0 (baseline), 4, and 8 mo in 68 patients. Counts of “definite” or “possible” Ma were made on films projected under standard conditions by two observers known to achieve consistently reproducible results. Semiquantitative assessment of diffusibility of fluorescein reflecting capillary leakage was performed in 61 patients. Leakage was graded according to three degrees of severity permitting study of observer variation, concordance of change in pairs of eyes, and treatment effects.
The average number of Ma at baseline was slightly higher in the continuous subcutaneous insulin infusion (CSII) group than in the conventional insulin treatment (CIT) group, but the difference was not statistically significant at the 0.05 level. At both 4 and 8 mo, definite Ma were more prevalent in the CSII group, and the difference was statistically significant at the 0.05 level using both parametric and nonparametric tests. In 27 CSII and 23 CIT patients having complete sets of 0, 4, and 8-mo photographs, Ma counts increased during the 0–4–mo interval. During the 4–8-mo interval, a further increase occurred in the CSII group but contrasted with a decrement observed in the CIT group, which showed no net change from baseline. Stratification of baseline data showed no influence of differing baseline Ma counts on these changes. Reproducible quantitation of fluorescein leakage was accomplished by one of three observers. In the CSII group, increased leakage was statistically significant in the right eyes only during the 0–8-mo interval (P &lt; 0.05).
These data suggest that CSII does not benefit and may produce deterioration in early diabetic retinopathy during 8 mo of treatment. The relatively slower rate of progression of the CIT group could not be explained on the basis of increasing nonperfusion with consequent poor filling of Ma. Nevertheless, changes in hemodynamic factors may explain these changes, which suggest short-term deterioration of early diabetic retinopathy. Whether this response is protracted will be apparent from long-term studies of effects of nearnormoglycemia.
Clinical Predictors of Retinopathy and Its Progression in Patients with Type I Diabetes During CSII or Conventional Insulin Treatment
Authors: Testa Marcia A , Puklin James E , Sherwin Robert S , Simonson Donald C ,   The Kroc Collaborative Study Group
Published: September 2013

Data from 70 type I diabetic patients with nonproliferative retinopathy participating in a multicenter clinical trial of control and complications were analyzed to test for associations of clinical variables with baseline levels and 8-mo changes in retinopathy. Predictor variables included age, duration of diabetes, systolic blood pressure, inpatient and outpatient plasma glucose levels, glycosylated hemoglobin (HbA1), M-values, serum cholesterol, serum triglycerides, and creatinine clearance. Retinopathy was assessed by fundus photography and graded at the Fundus Photograph Reading Center according to a detailed protocol. For the entire group, baseline retinopathy was positively correlated (P &lt; 0.05) with baseline systolic blood pressure, plasma glucose, HbA1, serum cholesterol, and duration of disease and negatively correlated with creatinine clearance. Conversely, during treatment, progression of retinopathy was negatively correlated (P &lt; 0.05) with mean levels during treatment of plasma glucose, HbA1, M-values, serum cholesterol, and with changes during treatment in plasma glucose and serum triglycerides. Two-group and three-group multivariate classification analysis of progression of retinopathy (improved or unchanged versus worsening—mild or moderate) indicated lower plasma glucose as the single best predictor of worsening of retinopathy (P &lt; 0.05), correctly classifying 71% of patients with positive progression. Decreased creatinine clearance during therapy was found to be the best discriminator between mild and moderate progression. Other multivariate models yielded specificity values of up to 71% and sensitivity values of up to 92%.
We conclude that associations among clinical predictors and retinopathy during short-term glycemic control differ strikingly from those at baseline. Furthermore, results from the classification analysis suggest that the progression of retinopathy is influenced by a complex interaction of clinical variables, rather than by glycemic control alone.
Effects of Anti-insulin Receptor Antibodies on In Vivo Insulin Metabolism
Authors: Boden Guenther , Shimoyama Ryushi , Ray Tarun K , Savage Richard C 
Published: September 2013

The effects of anti-insulin receptor antibodies (AIRA) on receptor binding and insulin metabolism were studied in two patients with the type B, severe insulin resistance syndrome. Insulin binding was determined using rat hepatocytes in primary culture and the patient's own red blood cells. Plasma and urinary insulin concentrations and metabolic clearance rates (MCR) were determined in the two patients and in four normal controls in response to infusions of insulin for 60–120 min at rates ranging from 1 to 925 mU/kg/min. In patient 1, basal insulin concentration was 1400 μU/ml. After infusion of 1, 10, and 925 mU/kg/min of insulin it rose to 3800, 5500, and 225,000 μU/ml, respectively. Respective MCRs were 19, 110, and 186 ml/min. In patient 2, basal insulin concentration was 440 μU/ml. After infusion of 1, 10, and 100 mU/kg/min of insulin it rose to 720, 2500, and 18,800 μU/ml, respectively. Respective MCRs were 193, 262, and 294 ml/min. In controls, basal insulin concentration was 4 ± 0.3 μU/ml. After infusion of 1 and 10 mU/kg/min of insulin, it rose to 82 ± 17 and 1288 ± 50 μU/ml. Respective MCRs were 950 and 630 ml/min. These data showed that, in patients with AIRA: (1) insulin metabolism took place at the same rate but at higher insulin concentrations than in normal controls, and (2) MCR increased with rising insulin concentration but remained subnormal even at the highest insulin concentrations. In contrast, MCR in normal controls decreased with increasing insulin concentrations.
The data suggest that prevention of insulin binding prevents insulin metabolism at physiologic insulin concentrations and that supraphysiologically elevated insulin concentrations are needed to activate nonreceptor mechanisms.
Rapid Effects of Insulin on the Cycling of the Insulin Receptor in a Human Monocyte Cell Line (U-937)
Authors: Livingston James N , Saran Bruce R , Rose Cheryl D , Anderson Clark L 
Published: September 2013

The insulin receptor and its regulation by insulin was studied in U-937 monocytes, a human cell line with properties similar to those of normal peripheraf blood monocytes. Treatment of this cell with insulin for 8–16 h produced an overall loss in the insulin receptor, i.e., a loss of receptors from the cell surface and internal pools. In contrast, short-term insulin treatment (15–30 min) caused a reduction in cell surface receptors but an increase in the internal receptors, as judged by pronase treatment at 4°C to distinguish receptor location. After the removal of insulin and pronase, the internalized receptors were rapidly reinserted back into the cell surface after warming to 37°C.
Further studies showed an insulin-mediated increase in fluid-phase pinocytosis as measured by horseradish peroxidase (HRP) uptake. The amount of HRP accumulation and the time course for this stimulation were similar to those for receptor internalization. These features plus other results suggest that the insulin-stimulated internalization of insulin receptors may require an acceleration in the rate of pinocytic vesicle formation.
Dynamics of Glucose-induced Insulin Release During the Spontaneous Remission of Streptozocin Diabetes Induced in the Newborn Rat
Authors: Portha Bernard , Kergoat Micheline 
Published: September 2013

Neonatal rats injected with streptozocin (STZ, 100 mg/kg) at birth exhibited an acute diabetes followed by a spontaneous remission. We have previously shown that this recovery from neonatal diabetes is due to B-cell regeneration and reaccumulation of pancreatic insulin stores starting from 3 to 5 days after birth. The B-cell population during this period is heterogeneous with both surviving B-cells that have escaped the toxic effect of STZ and newly formed B-cells. To evaluate to what extent this B-cell population is functionally normal, we have measured in vitro the dynamics of glucose-induced insulin secretion from pancreatic fragments of rats treated with STZ at birth. The insulin responses were tested at intervals after STZ treatment, from day 1 to day 21 using perifusion of pancreatic fragments, and on day 21 and at 5 mo using perfusion of isolated pancreas.
While the glucose-induced insulin release was completely obtunded (2% of the normal response)on day 1 after STZ, it could be demonstrated after day 3. Moreover, it increased as a function of age (6% and 36% of the normal responses on day 5 and day 14, respectively). This restoration of the insulin response to glucose closely paralleled the recovery of pancreatic insulin stores (6% and 51% of normal values, respectively, on day 5 and day 14). In sharp contrast with the lack of glucose response in vitro in the adult, glucose-induced insulin release was still detected on day21 regardless of the in vitro system used (perifusion or perfusion). Furthermore, on day 21 the B-cells of the STZ rats exhibited a tendency toward enhanced insulin response to arginine, which is a prominent feature in adult rats previously treated with STZ at birth.
The present observations make it unlikely that STZ treatment per se causes a chronic loss of the glucosesensitive insulin secretion mechanism in the surviving B-cells or in the newly formed B-cells. Moreover, as we have previously shown that in adult rats given a neonatal STZ treatment the B-cells exhibit a selective insensitivity to glucose in vivo, the present data support the notion that the pathogenesis of this lesion is caused by factors other than a primary toxic effect of STZ.
Regulation of Gluconeogenesis in Hepatocytes from Fasted Alloxan-diabetic Rats
Authors: Wernette-Hammond Mary Ellen , Lardy Henry A 
Published: September 2013

Hepatocytes from fasted, alloxan-diabetic rats were ipcubated in the absence of gluconeogenic substrates to deplete residual glycogen stores. Glucose production from lactate and pyruvate was enhanced in cells from diabetic rats relative to similarly treated hepatocytes from fasted, nondiabetic control rats. Gluconeogenesis from dihydroxyacetone, fructose, or glycerol was not increased but the formation of lactate plus pyruvate from dihydroxyacetone was decreased.
The stimulation of gluconeogenesis by exogenous fatty acids was decreased by diabetes. The rates of gluconeogenesis in the presence of lactate plus pyruvate plus oleate were equal in hepatocytes from diabetic and control rats and indicate that the maximal rate of gluconeogenesis was not increased.
With lactate plus pyruvate as substrates, stimulation of gluconeogenesis by norepinephrine or dibutyrylcAMP was not altered by diabetes. The catecholamine stimulation of gluconeogenesis from glycerol also was unaffected. In contrast, diabetes decreased the maximal stimulation of gluconeogenesis from dihydroxyacetone by dibutyryl-cAMP, glucagon, or norepinephrine and this decrease was proportional to the decreased production of lactate plus pyruvate. The concentrations of glucagon or norepinephrine required for half-maximal stimulation were not altered by diabetes. Thus, the hormonal stimulation of gluconeogenesis from dihydroxyacetone is decreased by diabetes, probably because of decreased pyruvate kinase activity, but the interaction of glucagon and norepinephrine with hepatocytes and the subsequent stimulation of gluconeogenesis from physiologic substrates is not impaired.
Effect of Norepinephrine on Ketogenesis, Fatty Acid Oxidation, and Esterification in Isolated Rat Hepatocytes
Authors: Oberhaensli Rolf D , Schwendimann Rita , Keller Ulrich 
Published: September 2013

Recent studies in man demonstrated a marked ketogenic effect of increased plasma norepinephrine concentrations as observed in diabetic ketoacidosis. Since this effect may have been due either to increased substrate supply for ketogenesis (lipolysis) or to direct hepatic activation of ketogenesis, the latter mechanism was examined in isolated rat hepatocytes. Incubation of hepatocytes with norepinephrine (10−7 to 10−4 M) resulted in a dose-dependent increase in conversion of the long-chain fatty acid [1−14C]palmitate into ketone bodies and CO2. Norepinephrine decreased [1-14C]palmitate conversion into triglycerides without affecting fatty acid uptake.
Norepinephrine enhanced ketogenesis from [1-14C]palmitate in a physiologic range of fatty acid concentrations (0.5–2.5 mM), but failed to affect fatty acid esterification to phospholipids or mono- and diglycerides. In contrast to long-chain fatty acids, oxidation of the medium-chain fatty acid [1-14C]octanoate to ketone bodies was not enhanced by norepinephrine, whereas CO2 production increased. The effect of norepinephrine on [1-14C]fatty acid oxidation was blocked by the a, receptor blocker prazosine. The results demonstrate that norepinephrine diverts long-chain fatty acids into the pathways of oxidation and ketogenesis away from esterification, suggesting enhanced carnitine-dependent mitochondrial fatty acid uptake. The studies using octanoate indicated that norepinephrine also enhanced fatty acid oxidation by increasing the flux of acetyl-CoA through the Krebs cycle.
The data suggest that stress-associated sympathetic activation and norepinephrine discharge, as observed in diabetic ketoacidosis, result in direct activation of ketogenesis in the liver.
Insulin Resistance and Impaired Insulin Secretion in Subjects with Histories of Gestational Diabetes Mellitus
Authors: Ward W Kenneth , Johnston Colin L W , Beard James C , Benedetti Thomas J , Halter Jeffrey B , Porte Daniel 
Published: September 2013

NIDDM is characterized by decreased insulin secretory responses to glucose and to nonglucose stimuli, hyperglucagonemia, and decreased tissue sensitivity to insulin. However, it hasbeen unclear which of these abnormalities, if any, precedes the others. Since women with histories of gestational diabetes mellitus (GDM) are at high risk for eventual development of NIDDM, we measured B- and A-cell function and tissue sensitivity to insulin in eight normoglycemic, postpartum women with recent histories of GDM and in eight control subjects pair-matched for age and percent of ideal body weight.
Fasting plasma glucose levels in subjects with former GDM tended to be slightly higher than in matched controls (98 ± 3 versus 92 ± 2 mg/dl, P = 0.07). Basal plasma insulin in subjects with former GDM was significantly higher than in controls (22 ± 4 versus 14 ± 2 μUml, P = 0.05). During an intravenous glucose tolerance test (IVGTT), relative first- and second-phase insulin responses to glucose were decreased in subjects with former GDM (2316 ± 560 versus 7798 ± 1036% of basal · min, P = 0.004; and 8340 ± 946 versus 14,509 ± 2556, P = 0.04). An index of sensitivity to insulin, S1, calculated from the IVGTT, was also lower in former GDM (1.23 ± 0.69 × 10 4 versus 3.58 ± 0.78 × 10−4 min−1μU/ml, P = 0.001).
Acute insulin responses to 5 g i.v. arginine were measured at plasma glucose levels of approximately 95, 215, and 600 mg/dl. The response at 600 mg/dl is termed the AIRmax andis used asan index of glucoseregulated insulin secretory capacity. Insulin responses to arginine at all glucose levels were similar in both groups. However, AIRmax, which was inversely correlated with S1 in controls, appeared low for the degree of insulin resistance informer GDM. Glucagon responses to arginine obtained at normoglycemia and suppressibility of such responses by hyperglycemia (600 mg/dl) were similar in both groups.
We conclude that women with histories of GDM, who are predisposed to NIDDM, have impairments both of insulin secretion and of insulin action before the development of overt hyperglycemia.
Glomerular Proteoglycans in Diabetes: Partial Structural Characterization and Metabolism of De Novo Synthesized Heparan-35SO4 and Dermatan-35SO4 Proteoglycans in Streptozocin-Induced Diabetic Rats
Authors: Klein D J , Brown D M , Oegema T R 
Published: September 2013

The metabolism of glomerular proteoglycans was studied in an effort to understand the mechanisms leading to reduction of glomerular basement membrane (GBM) heparan sulfate (heparan-SO4) proteoglycan in diabetes. Glomeruli were isolated from control and streptozocin-induced diabetic rats after exposure to [35S]sulfate. A pool of rapidly metabolized 35S-glycosaminoglycans (GAG), predominantly heparan-35SO4, was present in GBMs from controls but not diabetics, whereas intact isolated glomeruli from the two groups contained similar quantities of 35S-macromolecules after 4 and 16 h in vitro. Glomeruli from diabetics contained less 35S-proteoglycan than controls after 16 h in vivo. A more rapid disappearance of [35s[sulfate from serum and an increased inorganic sulfate concentration in diabetes may account for this difference.
Glomeruli from diabetics contained more heparan-35SO4 and less dermatan-35SO4 proteoglycan than control glomeruli in vitro. Diabetic glomerular heparan-35SO4 proteoglycan and its GAG chains had hydrodynamic sizes similar to controls (Mr, 13 and 1.25 × 104, respectively). A heparin-releasable heparan-35SO4 proteoglycan detected in isolated control glomeruli by gel electrophoresis was present in chase medium of glomeruli from diabetics in the absence of heparin.
Two dermatan-35SO4 proteoglycans were synthesized in vitro. One had size and charge properties similar to glomerular heparan-35SO4 proteoglycan. A second, larger dermatan-35SO4 proteoglycan accumulated in tissue over 16 h. It was partially excluded from Sepharose CL-6B columns and eluted from Sepharose CL-4B columns at Kav = 0.32. The hydrodynamic sizes of both tissue forms of dermatan-35SO4 proteoglycan were similar in diabetics and controls.
Differences in the biochemical characteristics of the major de novo synthesized glomerular proteoglycan pools could not be invoked to explain altered metabolism of GBM heparan sulfate in diabetic animals. These changes may result from diminished affinity of heparan sulfate proteoglycan for extracellular matrix or cell surfaces and may account for altered glomerular ultrafiltration properties in diabetes mellitus.