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K Rett

Publications and source records attributed to K Rett.

At least 55 records · Page 3Linked to original sources
PubMed1994

[How can primary prevention of coronary heart disease be improved in general practice?].

BACKGROUND: The basic issue of primary prevention strategies of coronary heart disease is an individually adapted cardiovascular risk factor management. However, transformation of these strategies by health care professionals is still insufficient, as was demonstrated by three studies performed in private practice. METHODS AND RESULTS: In oral glucose tolerance tests performed in 234 patients with essential hypertension who were under regular medical control, 25.6% turned out to have previously unknown diabetes and 41.4% had impaired glucose tolerance. In the remaining 33.3% with normal glucose tolerance, mean total serum cholesterol was 260 mg/dl. 82 patients with essential hypertension and known diabetes had a mean total serum cholesterol of 276 mg/dl. Neither cohort was under lipid lowering drugs. Out of 290 unselected patients treated for type II-diabetes in private practice, 62% were hypertensive. Of those, hypertension was not known untreated or not sufficiently treated in 78.2%. CONCLUSION: As a consequence, in patients at high cardiovascular risk, not only the "leading" disease (i.e. diabetes, hypertension, hyperlipidaemia), but also the concomitant constellation deserves attention and early intervention.

Adult↗
PubMed1994

Insulin-induced translocation of GLUT 4 in skeletal muscle of insulin-resistant Zucker rats.

The genetically obese Zucker rat (fa/fa) is an animal model with severe insulin resistance of the skeletal muscle. We investigated whether a defect of insulin-dependent glucose transporter (GLUT 4) translocation might contribute to the pathogenesis of the insulin-resistant state. fa/fa rats, lean controls (Fa/Fa) as well as normal Wistar rats were injected intraperitoneally with insulin and were killed after 2 or 20 min, respectively. Subcellular fractions were prepared from hind-limb skeletal muscle and were characterized by determination of marker-enzyme activities and immunoblotting applying antibodies against alpha 1 Na+/K+ ATPase. The relative amounts of GLUT 1 and GLUT 4 were determined in the fractions by immunoblotting with the respective antibodies. Insulin induced an approximately two-fold increase of GLUT 4 in a plasma membrane and transverse tubule enriched fraction and a decrease in the low density enriched membrane fraction in all three groups of rats. There was a high individual variation in GLUT 4 translocation efficiency within the groups. However, no statistically significant difference was noted between the groups. No effect of insulin was detectable on the distribution of GLUT 1 or alpha 1 Na+K+ ATPase. The data suggest that skeletal muscle insulin resistance of obese Zucker rats is not associated with a lack of GLUT 4 translocation.

Animals↗
PubMed1994

New aspects of insulin resistance in hypertension.

Primary hypertension is a frequent polygenic disease with strong genetic and environmental components. During the last decade, evidence has been increasing that insulin resistance as a marker of increased risk for Type 2 diabetes and cardiovascular atherosclerotic disease is present not only in individuals with obesity, Type 2 diabetes and impaired glucose tolerance, but also in the majority of the hypertensive population. Insulin resistance describes a tissue- and pathway-specific defect of glucose metabolism present in the so called 'metabolic syndrome'. Hyperinsulinaemia compensates for insulin resistance, leading to a cluster of undesirable processes predisposing to diabetes, atheroma and, directly or indirectly, hypertension. Candidate mechanisms whereby this metabolic syndrome might lead to hypertension include renal sodium retention, vascular hyperresponsiveness, arteriolar smooth muscle cell proliferation, altered cellular electrolyte transport and composition, stimulation of sympatho-adrenergic activity and growth promoting effects. Insulin per se does not appear to be the cause of elevated blood pressure as frequently seen in insulin-resistant states, but it may act with other factors to promote hypertension and atherosclerotic cardiovascular disease.

Animals↗
PubMed1994

Possible synergistic effect of ACE inhibition and calcium-channel blockade on insulin sensitivity in insulin-resistant type II diabetic hypertensive patients.

So-called insulin resistance is a frequent phenomenon and a marker of increased risk for both type II diabetes mellitus and atherosclerosis. Today, insulin resistance is widely understood as a tissue- and pathway-specific defect of insulin-stimulated glucose uptake into skeletal muscle that is compensated for by hyperinsulinemia, leading to a cluster of undesirable hypertensiogenic, diabetogenic, and atherogenic processes. Additional defects of insulin-stimulated muscle blood flow and cellular kation balance are presently attracting increasing awareness. Clinical and experimental evidence suggests that angiotensin-converting enzyme (ACE) inhibition ameliorates both insulin-stimulated skeletal-muscle glucose uptake and blood flow in insulin-resistant states by a direct stimulation of cellular glucose uptake, which appears to be kinin-mediated. This improvement of insulin sensitivity could mean not only improvement of glucose metabolism, but also reduction of chronically elevated serum insulin and the ensuing atherogenic consequences (hyper- and dyslipidemia, sympathetic overactivity, growth of vascular smooth-muscle cells, hypertension, etc.). Ca(2+)-channel blockers that do not increase heart rate appear to exert direct antiatherogenic effects while being metabolically neutral. Thus, the combination of Ca(2+)-channel blockade by sustained release verapamil and ACE inhibition by trandolapril in insulin-resistant type II diabetic patients with essential hypertension appears to be promising in terms of possible synergistic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

[The metabolic syndrome. Pathophysiologic causes, diagnosis, therapy].

The individual components of the metabolic syndrome such as central obesity, dyslipidemia with increased triglycerides and decreased HDL-cholesterol, hyperuricemia, hypertension and progressive glucose intolerance are markers for an increased risk of atheroma and type 2 (non-insulin-dependent) diabetes. All components, with the exception of hyperuricemia, are associated with skeletal muscle insulin resistance, leading to compensatory chronic hyperinsulinemia. Insulin resistance/hyperinsulinemia, in turn, is associated with a series of hypertensiogenic and atherogenic side effects, aggravating the individual components of the metabolic syndrome. From a more pathophysiologically orientated point of view, early identification of individuals obviously at risk for atheroma and type 2 diabetes, as well as early intervention aimed at the improvement of reduced insulin action may play a central role in an integrated life-style approach of primary prevention of atherosclerosis and type 2 diabetes.

Arteriosclerosis↗
PubMed1992

[Hypertension in metabolic syndrome. Etiology and consequences].

Essential hypertension in patients with the metabolic syndrome is regularly associated with other metabolic disorders. Thus, most hypertensives are overweight and have a glucose intolerance, while many have concomitant hyperproteinemia and dyslipoproteinemia. Up until fairly recently, it was not known that so-called insulin resistance is a common denominator both of metabolic risk factors and hypertension. In recent years, our knowledge about insulin resistance has spawned an equally convincing and fascinating multidimensional concept which reveals and plausibly explains complex relationships between metabolism, hypertension and the coronary risk.

Blood Glucose↗
PubMed1992

Normal insulin receptor tyrosine kinase activity and glucose transporter (GLUT 4) levels in the skeletal muscle of hyperinsulinaemic hypertensive rats.

The spontaneous hypertensive rat is an animal model characterized by a syndrome of hypertension, insulin resistance and hyperinsulinaemia. To elucidate whether in analogy to other insulin resistant animal models an inactivity of the insulin receptor kinase or an alteration of the glucose transporter (GLUT 4) level in the skeletal muscle might contribute to the pathogenesis of insulin resistance we determined insulin receptor kinase activity and GLUT 4 level in the hindlimbs of spontaneous hypertensive rats and normotensive control rats. Normotensive normoinsulinaemic Lewis and Wistar rats were used as insulin sensitive controls, obese Zucker rats were used as an insulin resistant control with known reduced skeletal muscle insulin receptor kinase activity. Binding of 125I-insulin, crosslinking of 125I-B26-insulin, autophosphorylation in vitro with 32P-ATP and phosphorylation of the synthetic substrate Poly (Glu 4: Tyr 1) were performed after partial purification of solubilized receptors on wheat germ agglutinin columns. GLUT 4 levels were determined by Western blotting of subcellular muscle membranes. Insulin receptors from spontaneous hypertensive rats compared to those from Lewis and Wistar rats showed no difference of the binding characteristics or the in vitro auto- and substrate phosphorylation activity of the receptor, while in the Zucker rats the earlier described insulin receptor kinase defect was clearly evident. Western blots of subcellular muscle membrane fractions with antibodies against GLUT 4 revealed no difference in transporter levels. These data suggest that insulin resistance in spontaneous hypertensive rats is caused neither by an insulin receptor inactivity nor by a decreased number of glucose transporters in the skeletal muscle.

Adenosine Triphosphate↗
PubMed1992

What is the clinical significance of insulin resistance?

Insulin resistance is a frequent phenomenon and a marker of increased risk for non-insulin-dependent diabetes mellitus (NIDDM) and atherosclerosis. According to recent estimations, not only individuals with obesity, NIDDM, and impaired glucose tolerance (IGT) but also one fourth of the "healthy" glucose tolerant and the majority of the hypertensive population are insulin resistant. Insulin resistance describes a tissue- and pathway-specific defect of glucose metabolism that is compensated for by hyperinsulinemia, leading to a cluster of undesirable hypertensiogenic, diabetogenic, and atherogenic processes. The initial defect can be directly measured by glucose clamp and other sophisticated techniques; the clinical syndrome may be derived from a network of related variables known to be associated with reduced insulin action. Because neither clamps nor serum insulin screenings will be available on a widespread basis, early diagnosis based on clinical criteria is crucial. A new interpretation of the "thrifty" genotype hypothesis may explain why insulin resistance, which formerly apparently represented an advantage in the evolutionary selection process, is such a frequent phenomenon. Improvement of impaired insulin action as a therapeutic principle may play a future central role in an integrated lifestyle approach of primary prevention of noncommunicable diseases such as NIDDM, hypertension, and atherosclerosis.

Coronary Disease↗
PubMed1990

[Effect of prostaglandin E1 on amino acid metabolism of human skeletal muscle].

The influence of an intraarterial infusion of PGE1 on the amino acid metabolism of human skeletal muscle was examined in healthy volunteers using the forearm technique. A continuous increase of perfusion from 2.9 +/- 0.1 ml/100 g x min to 5.4 +/- 1.5 after 60 min could be observed. Muscular amino acid balances were not changed after 30 min but significantly after 60 min of PGE1 infusion. Muscular release of most of the amino acids was reduced or shifted to an uptake. The accumulated balance of the amino acids showed a significant increase from -21.9 to +33.2 nmol/100 g x min after 60 min. Thus the infusion of PGE1 led to an inhibition of muscular proteolysis and/or to a stimulation of proteosynthesis. In view of the fact that kinines are released during exercise and are partially effective via prostaglandine liberation, the protein-anabolic effect of exercise might be explained by action of prostaglandins.

Adult↗
PubMed1990

[Essential hypertension and diabetes mellitus].

While the incidence of essential hypertension is not increased in type 1 diabetics, it is about three times as high in type 2 diabetics. Since in 50% of the cases, hypertension is present before the metabolic disorder becomes manifest, an association between the etiologies of the two disturbances was suspected as long as 65 years ago. A new understanding of the significance of insulin resistance and hyperinsulinemia suggests that the two conditions are part of a single metabolic disorder. This is supported by the fact that normal-weight hypertensives can also manifest insulin resistance, and they more often develop a type 2 diabetes mellitus. These facts urge us to re-think our therapeutic approach to hypertension, and to employ, as far as possible, only those substances that have no negative influence on the incidence of the metabolic disorder. With the introduction of ACE-inhibitors capable of improving insulin sensitivity, we now have, for the first time, the possibility of improving the prognosis of the metabolic syndrome. Moreover, their molecular mechanism of action provides initial clues as to the possible etiology of the syndrome.

Diabetes Mellitus, Type 1↗
PubMed1990

[ACE-inhibitors and glucose metabolism].

ACE-inhibitors exhibit their blood pressure-lowering activity not only via a reduction of angiotensin II but also via on increase of kinin levels. The latter are known to improve insulin action and hence carbohydrate metabolism in normal volunteers and diabetics. Accordingly, ACE-inhibitors display the same effects. As clinical trials show they are especially useful for the treatment of hypertension in diabetes mellitus.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Metabolic effects of kinins: historical and recent developments.

In 1928, Frey and co-workers discovered kallikrein in human urine and described its prolonged hypotensive effect in the dog. Four years later, the same authors first reported a blood glucose-lowering effect of orally administered kallikrein in diabetic patients. However, the observed blood glucose-lowering effect of kallikrein appeared to fade with repeated administration, and therefore its possible metabolic role was not further investigated and fell into disregard. One decade ago, experimental data yielded indirect evidence that the regulation of local skeletal muscle blood flow and glucose uptake during work was mediated by proteolytically cleaved kinins. Further experiments demonstrated that in insulin-resistant states such as postoperative stress and type II diabetes, reduced muscular insulin sensitivity was increased and partly restored by continuous low-dose infusion of synthetic bradykinin. Recent work showing that tissue kallikrein is present in a number of different tissue sites, including skeletal muscle and our own observation of local kinin overflow after muscle work in healthy subjects, but not in type II diabetics, support the concept of a skeletal muscle kallikrein-kinin system (KKS) that is locally activated upon contraction. Moreover, in isolated perfused rat heart preparations, favorable effects of kinins on myocardial glucose uptake, oxidation, and glycolytic flux have been reported. Most interestingly, cardioprotective effects of kinins have been observed and attributed to improved energy and substrate metabolism in ischemic hearts. Taken together, these data gave rise to the concept that tissue KKS might be involved in the local modulation of skeletal muscle and myocardial tissue blood flow and substrate metabolism, and that activation of the KKS is defective in insulin-resistant states.

Coronary Disease↗
PubMed1990

Effects of beta-blocking agents on insulin secretion and glucose disposal.

Non-selective and to a lesser extent selective beta-blockers are known to slightly deteriorate glucose metabolism. This may be of clinical relevance, since patients with essential hypertension suffer from reduced insulin-sensitivity and some studies showed an increased incidence of diabetes type II with beta-blocker-treated hypertensive patients. However, it is not clear whether this effect is due to hypertension per se or in addition by antihypertensive treatment. The possible mechanisms by which beta-blockers influence carbohydrate metabolism are discussed. Insulin secretion is inhibited by beta-blockers in vitro. However, no effect is seen in vivo in man. Hepatic glucose production in theory may be influenced, but no effect is demonstrable. Muscular glucose uptake could be reduced; some data exist showing reduced peripheral insulin sensitivity, although there are controversial results. In conclusion, a deterioration of carbohydrate metabolism by beta-blockers is established, the mechanism whereby remains obscure.

Adrenergic beta-Antagonists↗
PubMed1990

The effects of bradykinin and the ischemic isolated rat heart.

The converting enzyme not only converts angiotensin I into angiotensin II but also metabolizes bradykinin. Furthermore, the effects of ischemia on myocardial tissue damage can be modulated by converting enzyme inhibitors. It is unknown whether these effects of ACE-inhibitors are due to increased bradykinin production. In this paper we describe the effects of captopril on bradykinin production in the ischemic isolated rat heart. The reduced deleterious effects of ischemia by captopril were associated with a stimulated bradykinin production. Beneficial effects of bradykinin could be due to an improved perfusion or to an effect on cellular metabolism. Therefore, we conclude that this effect on kinins by ACE-inhibitors is of importance in modulating tissue damage during ischemia.

Angiotensin-Converting Enzyme Inhibitors↗