bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of food deprivation on rat plasma estrone fatty acid esters
Authors: Vilà R. , Adán C. , Grasa M. M. , Masanés R. M. , Esteve M. , Cabot C. , Fernández‐López J. A. , Remesar X. , Alemany M. 
Published: March 2003

SummaryThe present study was devised to determine whether the circulating levels of estrone fatty esters are modified by 6–48 h starvation in the rat, in parallel to changes in fat reserves, as a test to check the plausibility of its function as a ponderostat signal in the mammal. Food deprivation resulted in a decrease in glucose and triacylglycerols, rapid disappearance of liver glycogen and increases in fatty acids and, especially, 3‐hydroxybutyrate. Insulin and leptin decreased, corticosterone and free estrone increased from 6 h onwards and total estrone levels were maintained. Starvation reduced the lipid content of the rat by 25.6%. Plasma esterified estrone levels decreased more slowly, by 13% in 48 h, but its circulating mass decreased in the same proportion as the total lipid content of the rat. The small change in circulating estrone fatty esters is consistent with the postulated role of oleoyl‐estrone as a medium‐term ponderostat signal.
Effects of current therapeutic interventions on insulin resistance
Authors: Kobayashi M. 
Published: March 2003

SummarySummary.Although diet and exercise remain the cornerstones of type 2 diabetes therapy, attempts at lifestyle changes seldom result in the achievement of glycaemic control. As a result, the addition of pharmacological agents is usually necessary. Currently available treatment options improve glycaemic control in the short term; however, maintaining long‐term glycaemic control, halting disease progression, and preventing the complications of type 2 diabetes have all proven to be elusive therapeutic goals.For more than 30 years, sulphonylureas (SUs) have been first‐line therapy for the management of type 2 diabetes. These compounds control hyperglycaemia by stimulating insulin release from pancreatic β cells, and thus their benefits are limited to patients with preserved β‐cell function. Despite historic reliance on these agents to treat type 2 diabetes, long‐term use of SUs may desensitize β cells. The meglitinides (e.g. repaglinide) are a new class of non‐sulphonylurea secretagogues that bind to a different receptor on the β cell. Repaglinide has a short duration of action and may be useful for the treatment of postprandial hyperglycaemia. The biguanides (e.g. metformin) represent another class of antidiabetic agents and improve glycaemic control primarily by decreasing hepatic glucose output. Metformin and SUs provide similar glucose‐lowering effects, and, in combination, may provide additional benefits in some patients. Reducing the rate of glucose absorption with α‐glucosidase inhibitors (e.g. acarbose) has been explored as an alternative approach to the management of postprandial hyperglycaemia, but these agents do not address the primary defect in type 2 diabetes. Eventually, prolonged overproduction of insulin to compensate for hyperglycaemia leads to dramatically reduced β‐cell function, and exogenous insulin therapy is required.
Risk factors for vascular disease in patients with diabetes
Authors: Brown W. Virgil 
Published: March 2003

SummaryThe risks of cardiovascular and cerebrovascular disease in patients with diabetes are greater than those in persons without diabetes. This is due, in part, to the metabolic effects of insulin resistance. Other contributing factors include hyperglycaemia, dyslipidaemia, hypertension, hypercoagulability, homocysteinaemia, smoking, and obesity. Risk factor modification, where possible, can reduce the risk of complications of diabetes and macrovascular disease.
Differences in pharmacotherapy and in glucose control of type 2 diabetes patients in two neighbouring towns: a longitudinal population‐based study
Authors: Olsson J. , Lindberg G. , Gottsäter M. , Lindwall K. , Sjöstrand Å. , Tisell A. , Melander A. 
Published: March 2003

SUMMARY Aim  To compare prescribing, dosage and blood glucose levels in patients with type 2 diabetes in two communities with differences in anti‐hyperglycaemic drug utilization.Methods  A retrospective longitudinal (1984–1994) population‐based study in two neighbour towns in southern Sweden. The mean prescribed daily dose was expressed as a fraction of the Defined Daily Dose (DDD) for each drug.Results  In town A, prescribing of oral agents and insulin was predominantly made by one specialized diabetes clinician, while in town B it was spread among several different general practitioners and one specialist. Altogether 44 636 medical visits by 2348 patients were identified. In each town, about 40% of the patients were treated without anti‐hyperglycaemic drugs, about 40% with oral agents and about 20% with insulin. However, there were pronounced between‐town differences in dosage and glucose control. The mean prescribed daily dose of sulphonylurea monotherapy decreased gradually from ≈ 0.7 to ≈ 0.5 DDD in town B but remained ≈ 0.8 DDD in town A. The proportion of patients on both sulphonylurea and metformin increased substantially in town A but not in town B. In these patients, the mean prescribed daily dose of sulphonylurea exceeded 1.0 DDD in both towns, although it decreased with time in town B. The mean prescribed daily dose of insulin increased from 1.05 to 1.2 DDD in town A but remained virtually unchanged at 0.95 DDD in town B. The mean fasting blood glucose was lower in town A than in town B both overall (7.7 vs. 8.8 mmol/l), in those treated without any anti‐hyperglycaemic drugs (7.2 vs. 8.1 mmol/l), in those on sulphonylurea monotherapy (8.3 vs. 9.7 mmol/l) and in those treated with insulin (8.1 vs. 10.2 mmol/l).Conclusions  Glucose control in routine care was better when most patients were treated by a diabetes specialist and were exposed to more intense pharmacotherapy.
β3‐Adrenergic receptor gene polymorphism and type 2 diabetes in a Caucasian population
Authors: Oeveren van‐Dybicz A. M , Vonkeman H. E , Bon M. A. M , Van Den Bergh F. A. J. T. M , Vermes I 
Published: March 2003

Summary AimThe β3‐adrenergic receptor (β3‐AR) is suspected to play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. A mutation in the β3‐AR gene (Trp64Arg) has been associated with the capacity of weight gain and with early onset of noninsulin dependent diabetes mellitus (type 2 diabetes). In this study we investigated the prevalence of the two β3‐AR alleles in a Caucasian population and studied the association between the β3‐AR genotype and metabolic disorders (obesity and type 2 diabetes).MethodsGenomic DNA extracted from peripheral blood leucocytes of 200 Caucasian subjects (137 subjects with and 63 subjects without type 2 diabetes). The MvaI polymorphism of β3‐AR, which detects the Trp64Arg mutation, was determined by polymerase chain reaction (PCR). We studied the correlation between the Trp64Arg mutation and the body mass index (b.m.i. kg/m2).ResultsThere was no significant difference between the patients with type 2 diabetes and control subjects in the frequency of the Arg64 allele (5.5% and 4.8%, respectively). Within the group of type 2 diabetes patients were 14 subjects with the Trp64Arg mutation (b.m.i., mean ± s.d.: 31 ± 8.5 kg/m2) and 123 without the mutation (b.m.i. 29 ± 4.8). There was no association between the β3‐AR gene polymorphism and sex, obesity, blood pressure, glycohaemoglobin concentration, proteinuria.ConclusionOur results suggest that the Trp64Arg mutation is not a major determinant of metabolic disorders (type 2 diabetes, obesity) and chronic complications of type 2 diabetes in a Dutch population.
Anomalous lipoproteins in obese Zucker rats
Authors: Blay M. , Peinado‐Onsurbe J. , Julve J. , Rodríguez V. , Fernández‐López J. A. , Remesar X. , Alemany M. 
Published: March 2003

SummaryAims  Obesity is characterized by dislipoproteinaemia with increased cholesterol and triacylglycerol levels and lower chylomicra disposal rates. We studied here whether these alterations were related to lipoprotein number and/or size and composition.Methods  Plasma from lean and obese Zucker rats was fractionated into lipoprotein classes (chylomicra, very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL)) by differential centrifugation. The apoprotein and lipid composition of each fraction were measured. Lipoprotein particle size was estimated by dynamic light scattering and used to tabulate the mean diameter and volume of lipoprotein micelles. Particle mass was calculated from the density and volume. The mass of lipids and protein in each fraction/ml of plasma allowed the estimation of mean particle concentration and then the number of molecules of lipid and protein/unit of lipoprotein micelle.Results  A large part of hyperlipidaemia of obese rats is due to the accumulation of chylomicra: 1.3 ± 0.2 mg/ml in lean rats [LR] (34% of all lipoproteins) and 8.2 ± 0.9 mg/ml in the obese rats [OR] (66% of all lipoproteins). Lipid percentage composition of lipoproteins was similar in both groups. The particle size of LDL and HDL was much higher in OR than in LR: LDLs weighed 31.1 ± 7.5 ag (LR) vs. 273 ± 81 ag (OR), and HDLs weighed 31.7 ± 12.6 ag (LR) and 375 ± 103 ag (OR). In chylomicra and VLDL there was a relative scarcity of apoproteins in OR compared with LR. The whole architecture of LDLs is altered in OR, with a predominance of surface lipids: phospholipid and free cholesterol, and lower amounts of core lipids: triacylglycerols and cholesterol esters, with surface/core lipids ratios of 0.74 (LR) and 1.89 (OR). The consequences of anomalous LDL and HDL composition, size and overall structure may result in magnified lipoprotein metabolism alterations that hamper their ability to transfer apolipoproteins to larger chylomicra and VLDL, and to alter cholesterol transfer and binding of their apoproteins to cell surface receptors. The smaller number of LDL and HDL particles may further compound these difficulties and thus change the free to esterified cholesterol ratios observed in OR.Conclusions  The main conclusions of this study are the key importance of chylomicron analysis for a better understanding of the transfer of lipids, and the altered lipoprotein size and apoprotein distribution in obese rats, which seriously hamper cholesterol interchange, resulting in hypercholesterolaemia, and thus triggering even more far‐reaching consequences for the well‐being of the obese.
Do baseline serum leptin levels predict weight regain after dieting in obese women?
Authors: Mavri A. , Stegnar M. , Sabovic M. 
Published: March 2003

SUMMARY Aim  Weight loss achieved during weight reduction programme is difficult to maintain. We investigated the possible role of circulating leptin in failure or success in maintaining weight loss.Methods  Serum leptin levels were measured in 30 healthy premenopausal obese women before and after 12 weeks of dietary intervention and after 5 months of follow‐up.Results  After intervention body mass index (BMI) decreased from 30.6 to 25.4 kg/m2 (p < 0.01) and leptin levels decreased from 16.7 to 7.7 ng/ml (p < 0.01). After 5 months follow‐up 12 women regained reduced weight and 18 women maintained weight loss. In the regainers leptin levels increased again, but remained low in the maintainers. Baseline leptin concentrations were lower in the regainers than in the maintainers (12.1 vs. 21.2 ng/ml, p = 0.04). During intervention leptin levels decreased three times more in the maintainers than in the regainers, although weight loss was similar in both groups.Conclusions  This study shows that obese women who regain weight after dieting have significantly lower baseline leptin levels than women who maintain weight loss. Our results suggest that differences in leptin resistance might exist in similarly obese women which could influence the success of dieting.
Effects and serum levels of glibenclamide and its active metabolites in patients with type 2 diabetes
Authors: Jönsson A. , Hallengren B. , Rydberg T. , Melander A. 
Published: March 2003

SUMMARY Objective  To study the effects and serum levels of glibenclamide (Gb) and its active metabolites in patients on chronic Gb medication on different daily doses.Material and methods   Fifty patients with type 2 diabetes on regular Gb therapy (1.75–14.0 mg daily). Blood samples were taken immediately before and 90 min after regular Gb intake. A standardized breakfast was served 30 min after drug intake. Serum insulin and proinsulin levels were determined by ELISA methods without cross‐reactivities. Serum drug levels were determined by HPLC. Fischer's R to Z‐test (correlation coefficients) and paired Student t‐tests were used when comparing values within the entire group and unpaired non‐parametric Mann–Whitney tests were used when comparing high and low dose levels. A p‐value < 0.05 was considered significant.Results   There were significant correlations between daily Gb dose, on the one hand, and, on the other, HbAlc (r = 0.55), Δ‐insulin (r = − 0.59) and Δ‐proinsulin (r = − 0.52) levels. Significant correlations between Gb therapy duration and insulin (r = − 0.40) and proinsulin (r = − 0.34) secretion and between Gb dose and ratio proinsulin/insulin (RPI) at both time points (r = 0.32 and 0.30) were also found. The RPI was lower after Gb intake. In patients on ≥ 10.5 mg steady state serum metabolite levels (Ml and Ml + M2) were higher (29(0–120) and 33 (0–120) ng/ml) than those of Gb itself (18(0–64) ng/ml). A great inter‐subject variability in Gb levels at both time points was seen.Conclusions   Our results indicate that, in patients on chronic medication, Gb is capable of stimulating both insulin and proinsulin secretion; the effect on insulin release is relatively greater. The effect was more pronounced in patients on a low Gb dose, either because of less impaired β‐cells in those receiving low doses, or due to reduced sulphonylurea sensitivity in those on high dosage (down‐regulation). In patients on a daily dose of 10.5 mg or more, serum metabolite levels of clinical relevance were demonstrated; the metabolites may contribute to hypoglycaemic events.
Insulin‐like growth factor I, epidermal growth factor and transforming growth factor beta expression and their association with intrauterine fetal growth retardation, such as development during human pregnancy
Authors: Hernandez‐Valencia M. , Zarate A. , Ochoa R. , Fonseca M. E. , Amato Dante , De Jesus Ortiz M. 
Published: March 2003

Aim: Fetal intrauterine growth retardation (IUGR) is one of the most common obstetric problems, with a frequency of 12% in Mexico. In the past, investigations have focused on extrinsic causes of IUGR. More recent studies have examined the intrinsic factors that cause fetal intrauterine growth. Maintenance of fetal growth has been attributed to insulin‐like growth factor (IGF), epidermal growth factor (EGF) and transforming growth factor beta (TGF‐β). The objective of this study was to assess the levels of these growth factors during pregnancy and to determine whether or not low concentrations are associated with IUGR.Methods: Nine women whose pregnancies were complicated by IUGR and a group of nine women whose pregnancies exhibited normal fetal intrauterine growth were studied. IUGR was determined by sonography and confirmed by weight at birth. Venous blood samples were taken from both groups of pregnant women at the end of each trimester. Enzyme‐linked immunosorbent assays, immunoradiometric assays and radioimmunoassays were used to process samples, and the results were analysed by anova.Results: IGF‐I levels increased in both groups during pregnancy, but the increase was lower (p < 0.001) in the IUGR group throughout pregnancy and at delivery. EGF did not show any significant changes during pregnancy. Blood TGF‐β levels varied only during the first trimester of pregnancy. The differences were not statistically significant. However, TGF‐β concentrations were higher in the pregnancies with IUGR. Women in the IUGR group were smaller than in the control group (p < 0.05), and, using the covariance test (p < 0.05), this was found to be correlated with IGF‐I levels but not with EGF or TGF‐β levels.Conclusions: Changes in fetal weight might be explained by the different concentrations of IGF. The structural homology between IGF‐1 and insulin could mean that the presence of higher levels of IGF would result in a increased energetic metabolism that could contribute to fetal growth. EGF levels were not related to IUGR, and TGF‐β levels increased only during the first 3 months in the IUGR group. This observation correlates with the in vitro action of TGF‐β as a negative factor of growth, but as a positive support for sustaining early pregnancy. Our data illustrates that low height represents an increased risk factor for IUGR. These data also correlate with the studies involving extrinsic factors.
Identification of two novel and potent competitive inhibitors of the glucose‐6‐phosphatase catalytic protein
Authors: Westergaard N. , Madsen P. , Lundbeck J. M. , Jakobsen P. , Varming A. , Andersen B. 
Published: March 2003

Aim: In this study, we show that inhibitors of the glucose‐6‐phosphatase (G‐6‐Pase) catalytic protein could be an alternative approach to the recent G‐6‐Pase T1‐translocase inhibitors to target this enzyme for the treatment of type 2 diabetes.Method: The active enantiomers of 4‐methoxyphenyl‐[4‐(4‐methoxyphenyl)‐4,5,6,7‐tetrahydrothieno[3,2‐c]pyridin‐5‐yl]methanone (Compound A‐1) and 4‐methoxyphenyl‐[4‐(4‐trifluoromethoxyphenyl)‐4,5,6,7‐tetrahydrothieno[3,2‐c]pyridin‐5‐yl]methanone (Compound B‐1) were characterized as inhibitors of the G‐6‐Pase catalytic protein using pig and rat liver microsomes and cultured rat hepatocytes.Results: Both compounds were found to be potent competitive inhibitors of the G‐6‐Pase catalytic protein obtained from pig and rat liver microsomes. The Ki values (µM) were calculated to be 0.61 ± 0.02 and 0.63 ± 0.08 for compound A‐1 and B‐1 on intact pig microsomes, and 0.27 ± 0.02 and 0.29 ± 0.06 on disrupted pig microsomes. The corresponding values for rat liver microsomes were found to be 3.3 ± 0.6 and 4.0 ± 1.2 for compound A‐1 and B‐1 on intact microsomes, and 1.54 ± 0.1 and 1.21 ± 0.1 on disrupted microsomes. Compound A‐1 was also able to inhibit pyrophosphatase activities from both intact and disrupted microsomes with equal potency (IC50; 0.43–0.55 µm). Using cultured rat hepatocytes and glycerol as the substrate, these compounds were able to prevent glucose production up to 60% with a concomitant increase in the G‐6‐P content (2.3‐fold) using compound A‐1. No increase in glycogen levels was seen.Conclusion: These data demonstrated that these compounds were more potent inhibitors on G‐6‐Pase obtained from pig microsomes and were able to penetrate the microsomal membrane. The hepatocyte data further support the kinetic data, and are also consistent with the evoked mechanism of action.
2‐[18F]fluoro‐2‐deoxy‐d‐glucose combined with microdialysis can be used for the comparison of tissue glucose metabolism in obese and lean rats
Authors: Virtanen K. A. , Haaparanta M. , Grönroos T. , Bergman J. , Solin O. , Rouru J. , Nuutila P. , Huupponen R. 
Published: March 2003

Aims: Direct assessment of tissue metabolism in vivo is important to understand the pathogenesis of obesity. Labelled glucose analogues are potential candidates to be used for this purpose. The aim of this study was to compare the kinetics and metabolism of 2‐[18F]fluoro‐2‐deoxy‐d‐glucose (FDG) in obese (fa/fa) and lean (Fa/?) Zucker rat tissues with microdialysis, and the measurement of uptake and phosphorylation with or without insulin bolus injection.Methods: Obese (n = 10) and lean (n = 11) anaesthetized rats underwent a microdialysis study after FDG‐injection either with or without insulin stimulation. Microdialysis probes were inserted in the jugular vein, quadriceps muscle and liver. After 110 min, tissue [18F]‐uptake and intracellular phosphorylation of FDG were studied in blood, liver, skeletal muscle, subcutaneous adipose tissue, intra‐abdominal adipose tissue and hypothalamus.Results: When measured with microdialysis, insulin‐enhanced FDG disappeared from the blood pool and interstitial space of skeletal muscle and liver more effectively in lean rather than in obese animals. Insulin‐stimulated skeletal muscle and adipose tissue[18F]‐uptake was impaired in obese Zucker rats compared with lean animals. Hypothalamic FDG uptake was six to sevenfold higher than in other measured tissues, but was attenuated in obese rats. In liver and in mesenteric fat, insulin‐enhanced FDG phosphorylation in lean rats compared with obese animals.Conclusions: Positron‐emitting glucose analogue FDG, combined with microdialysis and tissue analysis, is a feasible method in studying glucose metabolism at the cellular level in animal studies.
Effects of arachidonic acid plus zinc on glucose disposal in genetically diabetic (ob/ob) mice
Authors: Hwang I. K. , Go V. L. W. , Harris D. M. , Yip I. , Song M. K. 
Published: March 2003

Aim: The present study is designed to determine whether arachidonic acid (AA) plus zinc improves clinical signs of diabetes in genetically diabetic ob/ob mice.Methods: In the first study, effects of acute administration of AA plus zinc on glucose disposal were determined in ob/ob and lean mice (n = 6 each). In the second study, ob/ob and lean mice were treated with increasing doses of AA plus zinc for 2 weeks (n = 5 each). Postprandial and fasting blood glucose concentrations, three‐hour‐area‐average above fasting glucose concentration (TAFGC), water and food intake, body weight and plasma insulin concentrations were measured.Results: Acute administration of AA plus zinc significantly increased glucose disposal in ob/ob mice. In the second study, postprandial and fasting blood glucose concentrations, TAFGC, and water and food intake in ob/ob mice treated with AA plus zinc for 2 weeks were significantly decreased compared with those in mice given no AA. Plasma insulin concentrations in both lean and ob/ob mice were not changed by AA treatment in drinking water.Conclusions: AA plus zinc in drinking water is effective in decreasing blood glucose levels in obese mice. These results indicate that use of these compounds should be considered as a dietary supplement to control hyperglycaemia in patients with type II diabetes.