bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relation between insulin resistance and cardiovascular complications of the insulin resistance syndrome
Authors: Rett K. 
Published: March 2003

SummarySummary. It has been known for years that cardiovascular disease frequently precedes the development of type 2 diabetes, and that atherosclerosis might not be a complication of type 2 diabetes, but rather the consequence of common genetic and environmental factors (the ‘common soil’ hypothesis). The insulin resistance syndrome (IRS) is a cluster of closely associated and interdependent abnormalities, including insulin resistance, hyperinsulinaemia, android fat distribution, progressive glucose intolerance, dyslipidaemia (increased triglycerides, decreased HDL, increased small dense LDL), increased prothrombotic and antifibrinolytic factors, and hypertension. Many of these abnormalities are risk factors for type 2 diabetes, and most of them explain the predilection for atherosclerosis to occur in conjunction with IRS. Insulin resistance is a key feature of IRS, and has been suggested to be the common pathophysiological basis of atherosclerosis and type 2 diabetes. The term ‘insulin resistance’ denotes resistance to insulin‐mediated glucose uptake into skeletal muscle, which can be measured by the glucose clamp technique. There are, however, other less understood sites of abnormal insulin action that may also be relevant in IRS. These include liver, adipose, and kidney tissue, and systems such as muscle perfusion, antilipolysis, lipoprotein lipase activity, and cation transport. The development of clinical cardiovascular end‐points in a patient with insulin resistance is complex, as it includes the degree of the defect, its associated abnormalities, its consequences, and the ability to compensate for the underlying defect. It is therefore more appropriate to consider the different facets and risk factors of IRS in aggregate, rather than seeking ‘independent’ effects. Accordingly, treatment of insulin resistance per se has not yet been shown to reduce the incidence of cardiovascular complications. At the cellular level, excess insulin is involved in various elements of atherogenesis. It interacts with cytokines and growth factors in a cross talk among vascular wall cells and a variety of mediators that play a role in the establishment of atheroma. Excess insulin also plays an important role in concert with lipoproteins when they exhibit an abnormal pattern and become modified by oxidation and glycation. It is therefore currently hoped that the introduction of a new class of insulin‐sensitizing agents, the thiazolidinediones, may attenuate these processes. The thiazolidinediones act through ligand activation of a nuclear transcription factor, the peroxisomal proliferator‐activated receptor‐γ (PPARγ). Although this receptor was initially linked to lipid and glucose metabolism, recent data suggest that PPARγ is also involved in the differentiation of mononuclear phagocytes, their inflammatory reactions, and macrophage conversion to foam cells. Thus, PPARγ ligands may also be important regulators of monocyte/macrophage gene expression during atherogenesis.
Short‐term hypothyroidism has no effect on serum leptin concentrations
Authors: Simó R. , Hernández C. , Zafon C. , Galofré P. , Castellanos J. M. , Mesa J. 
Published: March 2003

SummaryThe aim of the study is to determine the effect of short‐term hypothyroidism on serum leptin levels. For this purpose 30 patients with past medical history of thyroidectomy for differentiated thyroid carcinoma were included. Serum leptin concentrations were similar when patients were on thyrotrophin‐suppressive thyroxine therapy than when were admitted 4 weeks after stopping thyroxine treatment to perform a routine 131I scan in hypothyroid status (17.0 ± s.e.m. 2.14 vs. 17.6 ± s.e.m. 2.41 ng/ml; p = n.s.). Moreover, no differences were obtained when the analysis was performed separately in men and in women. We conclude that short‐term hypothyroidism does not alter serum leptin concentrations. Furthermore, our results suggest that thyroid hormones do not operate through changes in serum leptin levels to regulate energy expenditure.
Rosiglitazone prevents the onset of hyperglycaemia and proteinuria in the Zucker diabetic fatty rat
Authors: Smith S. A. , Lister C. A. , Toseland C. D. N. , Buckingham R. E. 
Published: March 2003

Summary Aim  To investigate the potential of rosiglitazone, a highly potent agonist at the nuclear peroxisome proliferator activated receptor‐γ (PPAR‐γ), to prevent the development of diabetes in the Zucker diabetic fatty (ZDF) rat or to ameliorate the condition at a later stage of the disease.Methods  Rosiglitazone (10 μmol/kg body weight daily) was given via the diet to ZDF rats from aged 6 weeks, before the onset of hyperglycaemia (Prevention group), or from aged 21 weeks after hyperglycaemia and proteinuria were established (Intervention group). Untreated ZDF rats and age‐matched Zucker lean rats (ZL) served as controls and the experiment was terminated when the animals were aged 28 weeks.Results  Whilst the combined ZDF control and Intervention groups were already hyperglycaemic (14.6 ± 1.6 vs. ZL 5.7 ± 0.1 mmol/l, mean ± s.e.m.; p < 0.05), glycosuric and polydipsic at aged 11 weeks, and thereafter had a declining plasma insulin concentration, rosiglitazone Prevention treatment maintained normoglycaemia even at aged 27 weeks (3.7 ± 0.3 mmol/l vs. ZL 3.0 ± 0.3 mmol/l; NS). Intervention treatment at aged 21 weeks, however, failed to ameliorate the diabetes. These functional data were supported by determinations of pancreatic insulin content (μg/mg tissue as follows: ZL, 43.1 ± 3.9; ZDF control (28 weeks) + ZDF Intervention control (21 weeks), 6.0 ± 0.8; Prevention, 63.6 ± 15.8; Intervention, 6.2 ± 0.9) and by morphological, immunohistochemical and electron microscopical examination of pancreata at the end of the study. Thus, islets from rosiglitazone Prevention rats were similar to ZL rats, whereas ZDF controls and Intervention rats exhibited islets depleted of insulin, with a disorganized architecture and an ultrastructure indicative of work hypertrophy. ZDF control rats and Intervention rats, though not rosiglitazone Prevention rats, also exhibited marked proteinuria, indicative of renal glomerular damage.Conclusions  Our results demonstrate that in ZDF rats, rosiglitazone prevents the progression from insulin resistance to overt diabetes. These data provide a rationale for investigating whether treatment with rosiglitazone of patients with early signs of perturbed glucose metabolism (e.g. impaired fasting glucose (IGT)) may prevent the progression to type 2 diabetes and its associated complications.
Insulin release and suppression by tacrolimus, rapamycin and cyclosporin A are through regulation of the ATP‐sensitive potassium channel
Authors: Fuhrer D. K. , Kobayashi M. , Jiang H. 
Published: March 2003

Summary Aim  By focusing on the pancreatic β cell response to tacrolimus, cyclosporin A (CsA) and rapamycin we hoped to identify immunophilin, calcineurin and/or novel mechanism involvement and advance the understanding of immunosuppressant regulated insulin control.Methods  A glucose responsive β cell model was established in which the glucose response was blocked by immunosuppressant treatment and this model was used to further characterise this effect. Quantification of insulin release to immunosuppressants and specific inhibitors was used to identify the mechanism involved.Results  It was found that upon the addition of tacrolimus, rapamycin, or CsA, rapid and significant exocytosis of cellular insulin was seen. A dose response study of this effect revealed optimal concentration windows of 50– 80 nm for tacrolimus, 100–300 nm for rapamycin, and 7–12 mm for CsA in RIN‐5F cells. Optimal insulin release for HIT‐T15 cells was similar. Additional experiments demonstrate that immunosuppressant pretreatment blocked the subsequent immunosuppressant induced insulin release but not that of a thapsigargin control, suggesting that suppression and release are non‐toxic, specific and in the same pathway. Further experiments showed that this insulin release was a calcium dependent process, which was blocked by inhibitors of l‐type calcium channels. Continued studies showed that the specific ATP‐sensitive potassium channel agonist diazoxide (150 mm) also blocked immunosuppressant‐induced insulin release.Conclusions  A model that fits this data is a novel calcineurin‐independent immunophilin mediated partial closing of the ATP‐sensitive potassium channel, which would lead to an initial insulin release but would reduce subsequent responses through this pathway.
Effect of acarbose on weight maintenance after dietary weight loss in obese subjects*
Authors: Hauner H. , Petzinna D. , Sommerauer B. , Toplak H. 
Published: March 2003

SUMMARY Aims   Acarbose is a well established antidiabetic drug and is known to exert a modest weight‐lowering effect. The aim of this study was to assess the potential of acarbose to improve weight maintenance after a substantial weight loss by dietary measures in obese subjects.Design   Randomised, double‐blind, placebo‐controlled trial of the effect of acarbose on weight change over a 6‐month follow‐up period.Patients and Methods   One hundred and ten obese subjects with a BMI ≥ 32 and ≤ 38 kg/m2 were included in the study and underwent a 10–16‐week very‐low‐calorie diet programme to initiate weight loss. Then, subjects were randomised to receive either acarbose or placebo for 26 ± 2 weeks. The primary variable was body weight. The primary efficacy analysis was performed in the per‐protocol population (n = 75).Results   After an initial mean weight loss of 10.0 ± 3.4 kg, 54 subjects received acarbose at increasing dosage and 56 subjects received placebo treatment. After 14 weeks of follow‐up, there was no change in body weight in the two groups. After 26 weeks, completed by 37 subjects in the acarbose group and by 38 subjects in the placebo group, a small weight regain of 0.6 kg was documented in the latter, whereas no weight increase was observed under acarbose treatment (p = 0.38, analysis of covariance with initial body weight as covariable).Conclusion   In obese individuals who undergo a hypocaloric diet and achieve a substantial loss of body weight, acarbose treatment provides only a very modest, not significant benefit to stabilise weight reduction. Thus, acarbose is not a useful adjunct to improve weight maintenance in obese subjects after weight loss.
The effects of orlistat on body weight and glycaemic control in overweight patients with type 2 diabetes: a randomized, placebo‐controlled trial
Authors: Hanefeld M. , Sachse G. 
Published: March 2003

Aim: To assess the long‐term effects of orlistat on body weight, glycaemic control and cardiovascular risk factors in overweight patients with type 2 diabetes.Methods: This was a multicentre, randomized, placebo‐controlled study with a 4‐week placebo plus diet lead‐in period and a 48‐week, double‐blind treatment period. Overweight or obese adults [body mass index (BMI) ≥ 28 kg/m2] with HbA1c of 6.5–11% and clinical type 2 diabetes were randomized to orlistat (120 mg t.i.d. n = 189) or placebo (n = 180) in conjunction with a low‐calorie diet. Patients had either received sulphonylurea therapy for at least 2 months before the study or were not receiving any antidiabetic medication (the majority of which were drug‐naïve).Results: After 1 year, patients in the orlistat group lost significantly more weight than patients in the placebo group (−5.4% vs. −3.6%; p = 0.006). Moreover, significantly more patients achieved weight loss of ≥ 5% with orlistat compared with placebo (51.3% vs. 31.6%; p = 0.0001). Patients treated with orlistat also had significantly greater improvements than placebo‐treated patients in HbA1c (−0.9% vs. –0.4%; p < 0.001), fasting glucose (−1.6 vs.–0.7 mmol/l; p = 0.004) and post‐prandial glucose (−1.8 vs. –0.5 mmol/l; p = 0.003). In addition, orlistat‐treated patients had a significantly greater reduction in LDL cholesterol compared with placebo. Overall, orlistat had a similar safety profile to placebo, with the exception of a higher incidence of generally mild and transient gastrointestinal events known to be associated with the mode of action of orlistat.Conclusions: Treatment with orlistat plus diet resulted in significant weight loss, improved glycaemic control and cardiovascular risk factor profile in overweight patients with type 2 diabetes.
Rosiglitazone (PPARγ‐agonist) attenuates atherogenesis with no effect on hyperglycaemia in a combined diabetes–atherosclerosis mouse model
Authors: Levi Z. , Shaish A. , Yacov N. , Levkovitz H. , Trestman S. , Gerber Y. , Cohen H. , Dvir A. , Rhachmani R. , Ravid M. , Harats D. 
Published: March 2003

Background: The administration of peroxisome proliferator‐activated receptor γ (PPARγ) agonists to low‐density lipoprotein (LDL)‐receptor‐deficient mice resulted in a reduction in the atherosclerotic lesion area in male mice, but not in female mice. The male mice also exhibited reduction in insulin resistance while the female mice did not. To further examine the relationship between PPARγ agonists, insulin resistance and atherosclerosis, we used the model of accelerated atherosclerosis in male apolipoprotein E (apoE)‐deficient mice rendered diabetic by low‐dose streptozotocin (STZ).Methods: Male, apoE‐deficient mice (n = 48) were randomly divided into four groups. To induce diabetes, two groups received low‐dose STZ and two groups served as controls. After diabetes induction, rosiglitazone (a PPARγ agonist) was administered by oral gavage to one of the diabetic and one of the non‐diabetic groups.Results: Rosiglitazone reduced significantly the atherosclerotic aortic plaque area in both diabetic and non‐diabetic apoE‐deficient mice: 340 ± 54 vs. 201 ± 27 μmol2 (p = 0.001) in diabetic mice; 243 ± 22 vs. 158 ± 27 μmol2 (p = 0.001) in non‐diabetic mice. Also, rosiglitazone reduced the correlation coefficient between plasma glucose and the degree of atherosclerosis (p < 0.0025) without affecting plasma glucose levels. The rosiglitazone‐treated mice, both diabetic and non‐diabetic, had higher lipid levels.Conclusions: Rosiglitazone‐treated animals showed less atherosclerosis despite higher lipid levels and similar glucose levels. These data suggest a direct anti‐atherogenic effect of rosiglitazone on the arterial wall.
The pedal muscle of the land snail Megalobulimus oblongus (Gastropoda, Pulmonata): an ultrastructure approach
Authors: Faccioni‐Heuser M. Cristina , Zancan Denise M. , Lopes Christiane Q. , Achaval Matilde 
Published: March 2003

M. Cristina Faccioni‐Heuser, Denise M. Zancan, Christiane Q. Lopes and Matilde Achaval. 1999. The pedal muscle of the land snail Megalobulimus oblongus (Gastropoda, Pulmonata): an ultrastructure approach. — Acta Zoologica (Stockholm) 80: 325–337The ultrastructure of the pedal muscle of the Megalobulimus oblongus is described. This muscle consists of transverse, longitudinal and oblique bundles ensheathed in collagenous tissue. Each muscle cell is also ensheathed by collagen. The smooth muscle cells contain thin and thick filaments; the thin filaments are attached to dense bodies. These cells contain a simple system of sarcoplasmic reticulum, subsarcolemmal caveolae and mitochondria with dense granules in the matrix, and glycogen. Three types of muscle cells were identified. Type A cells exhibited densely packed myofilaments, abundant glycogen rosettes, numerous mitochondria and sarcoplasmic reticulum profiles. Type B cells exhibited scanty glycogen and mitochondria, few cisternae of sarcoplasmic reticulum and large intermyofibrillar spaces. Type C cells exhibited intermediate characteristics between type A and type B cells. Neither nexus nor desmosomes were observed between the muscle cell membranes. The muscle contains well developed connective tissue and blood vessels. These structures and the distribution of muscle cells are probably involved in the muscular‐hydrostat system. The muscle is richly innervated, having neuromuscular junctions with clear and electron‐dense synaptic vesicles. The clear vesicles probably contain acetylcholine because the axons to which they are connected arise from acetylcholinesterase positive neurones of the pedal ganglion. The other vesicles may secrete monoamines such as serotonin and/or neuropeptides such as substance P.
The mesopneumonia and the post‐hepatic septum of the Teiioidea (Reptilia: Squamata)
Authors: Klein Wilfried , Böhme Wolfgang , Perry Steven F. 
Published: March 2003

AbstractKlein, W., Böhme, W. and Perry, S. F. 2000. The mesopneumonia and the post‐hepatic septum of the Teiioidea (Reptilia: Squamata). —Acta Zoologica(Stockholm)81: 109–119This study investigates the structure of the pleuroperitoneal cavity of Teiioidea. Seven of nine genera of Teiidae and eight of 35 genera of Gymnophthalmidae were dissected and the results are presented in a highly schematic two‐dimensional representation. The main anatomical differences between the two families are (1) the presence of a hepatic ligament which fuses with the pericardiaco‐peritoneal septum in the Gymnophthalmidae but not in the Teiidae; (2) the presence of a ventral mesopneumonium on the right side in the Gymnophthalmidae, while this structure is secondarily lacking in the Teiidae; (3) that the post‐hepatic septum of Teiidae consists of a bipartite hepatic ligament and the ventral mesentery, while in gymnophthalmids the hepatic ligament remains undivided.NeusticurusandEchinosauracompletely lack a post‐hepatic septum. The results are consistent with the hypothesis that the Gymnophthalmidae are primitive within the Teiioidea and that the Tupinambinae are the most highly derived teiids. We propose that the post‐hepatic septum may restrict passive visceral movement during breathing, thereby increasing the efficiency of respiratory effort; a modification that could benefit the fitness of active, predatory teiids.
Locomotory design of ‘cyclostome’ fishes: Spatial arrangement and architecture of myosepta and lamellae
Authors: Vogel Felix , Gemballa Sven 
Published: March 2003

AbstractVogel, F. and Gemballa, S. 2000. Locomotory design of ‘cyclostome’ fishes: Spatial arrangement and architecture of myosepta and lamellae. —Acta Zoologica (Stockholm) 81: 267–283In recent years, it has been established that the main features of the locomotory apparatus of gnathostome fishes (myoseptal and muscular system) have remained relatively unchanged throughout evolution. The petromyzontiforms (lampreys) and myxiniforms (hagfishes) display a similar way of undulatory locomotion as gnathostomes. We investigated whether the anatomical features of the myoseptal system that facilitate undulatory locomotion in gnathostomes are also present in lampreys and hagfishes. We present a description of the myoseptal system, including for the first time the spatial arrangement and fibre architecture in ‘cyclostomes’, using a clearing technique, microdissections, polarized light microscopy, and SEM. We revealed that the myoseptal system of the Myxiniformes, Petromyzontiformes and Gnathostomata are each constructed in different ways. Petromyzontiform myosepta lack the conical structures but bear tendon‐like structures in the flanking parts. Their central parts lack tendon‐like structures but possess a system of crossing collagen fibres. Myxiniform myosepta bear comparable conical structures as gnathostomes but a highly asymmetric spatial arrangement. The fibre architecture of myosepta is not comparable to any of the two remaining taxa. The collagen fibre architectures of the multiple horizontal sheets of lamellae in ‘cyclostomes’ and the gnathostome horizontal septum are comparable. Our results 1) support the monophyly of Myopterygii (Petromyzontiformes + gnathostomes and a sistergroup relationshop of Myopterygii and Myxiniformes; 2) demonstrate that considerable changes must have taken place in the locomotory apparatus early in vertebrate evolution.
Locomotory and feeding effectors of the tornaria larva of Balanoglossus biminiensis
Authors: Lacalli T. C. , Gilmour T. H. J. 
Published: March 2003

AbstractLacalli, T. C. and Gilmour, T. H. J. 2001. Locomotory and feeding effectors of the tornaria larva of Balanoglossus biminiensis. —Acta Zoologica (Stockholm) 82: 117–126The tornaria ciliary bands and oesophagus were examined ultrastructurally to identify the neural components that control larval behaviour. The circumoral ciliary band is known to be innervated in part by fibres from the apical plate and adoral nerve centres. Within the band itself, however, the only neurones we could find were multipolar cells, an unusual cell type with apical processes that traverse the surface of the band. Similar cells occur in the circumoral bands of echinoderm larvae. The tornaria telotroch has a much larger nerve, but no neurones were found either in the band or nearby, so the source of the fibres in the telotroch nerve remains unknown. In addition to having different innervation, the two bands also respond differently to cholinergic agonists, which elicit telotroch arrests but have no visible effect on the circumoral band. The oesophagus has a well‐developed musculature and an extensive nerve plexus. During feeding, the oesophagus repeatedly contracts, forcing excess water out along two lateral channels prior to swallowing. These channels are also sites of gill slit formation, so there is evidently a continuity between the water bypass mechanism of the larva and that of the postmetamorphic juvenile.
Functional morphology of the male genitalia and copulation in lower Hymenoptera, with special emphasis on the Tenthredinoidea s. str. (Insecta, Hymenoptera, ‘Symphyta’)
Authors: Schulmeister Susanne 
Published: March 2003

AbstractA general description of the male reproductive organs of lower Hymenoptera is given. The terminology of the male genitalia is revised. The male external genitalia of Tenthredo campestris are treated in detail as a specific example of the morphology. The interaction of the male and female parts during copulation is described for Aglaostigma lichtwardti. The possible function of sclerites and muscles of the male copulatory organ of Tenthredinoidea s. str. is discussed. Additional observations on morphology and function made in non‐tenthredinoid lower Hymenoptera are included. The assumption that the gonomaculae act as suction cups is confirmed for the first time. The evolution of obligate and facultative strophandry is discussed. The stem species of all Hymenoptera was probably orthandrous and facultatively strophandrous.
Minireview: On the homology of the protocoel in Cephalochordata and ‘lower’ Deuterostomia
Authors: Stach Thomas 
Published: March 2003

AbstractHypotheses regarding the homology of the protocoel in planktonic deuterostome larvae and mesodermal structures in ontogenetic stages of cephalochordates are evaluated. The prevalent ‘classical’ hypothesis describes the protocoel as being homologous with the diverticula of Hatschek, which, on the left side, develop into the preoral pit, subsequently into Hatschek’s pit and groove (in part). This hypothesis is based mainly on the position of Hatschek’s diverticula anterior to the rest of the mesoderm during their enterocoelic origin. It is shown here that during development the mesodermal segment that develops into Hatschek’s nephridium is the most anterior one prior to formation of Hatschek’s diverticula, and this segment assumes an anteriormost position after differentiation of Hatschek’s diverticula. Additional similarities between this segment and protocoels are: (i) presence of endomesodermal cells with podocytic extensions, (ii) excretory function, (iii) relatively early ontogenetic origin, (iv) probable lack of association with nervous structures, (v) probable ectodermal origin of a portion of the canal, and (vi) position relative to the mouth opening. Therefore, homology between the protocoel and the segment that becomes Hatschek’s nephridium is proposed. It is concluded that a glandular structure homologous to the diverticula of Hatschek and anterior to the protocoel/Hatschek’s nephridium is a synapomorphy of notochordates or chordates.