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Biomedical subjects

K Rett

Publications and source records attributed to K Rett.

90 records · Page 5Linked to original sources
PubMed1987

Captopril enhances insulin responsiveness of forearm muscle tissue in non-insulin-dependent diabetes mellitus.

Bradykinin infusion has been shown to improve glucose metabolism in non-insulin-dependent diabetic subjects (NIDD). Therefore, we tested the following hypothesis: inhibition of Kininase II, the bradykinin (BK) degrading enzyme, by captopril may also improve glucose metabolism in NIDD. Immediate effects of captopril on total body and peripheral glucose disposal were examined in five normotensive, normal weight NIDD and compared with five NIDD control subjects, well matched for age, weight and degree of fasting hyperglycaemia. The euglycaemic insulin clamp technique was employed in combination with the forearm catheter technique. After 90 min of insulin infusion a single dose of 25 mg captopril was administered orally, whereas in the control group a placebo was given. Captopril lead to a significant rise in total body glucose disposal and forearm glucose uptake, while in the control group no change was observed. Simultaneously, captopril lead to reduction in muscular release of lactate and pyruvate. We conclude that these results demonstrate the stimulatory effect of captopril on insulin-induced glucose disposal of the whole body, which appears to be a result of increased glucose utilization by peripheral tissues. Because of the described insulin-like activity of bradykinin, the concomitant accumulation of local kinins by captopril-induced inhibition of kininase II may represent an attractive hypothesis to explain the generated data sufficiently.

Alanine↗
PubMed1987

Inhibition of muscular amino acid release by lipid infusion in man.

Amino acid balances of healthy postabsorptive volunteers were investigated with the forearm technique under the influence of an intravenous infusion of triglyceride emulsions (LCT; MCT/LCT) [corrected]. A decrease of the basal muscular release of most of the amino acids, respectively an increase of pre-existent uptake rates [corrected]. In parallel, arterial concentrations of these amino acids declined. With constant insulin levels and substantially unchanged blood glucose levels, this inhibition of muscular proteolysis and/or stimulation of proteosynthesis is most probably due to the increased level of free fatty acids.

Amino Acids↗
PubMed1987

[Captopril in hypertensive patients with type II diabetes mellitus].

Since the angiotensin converting enzyme (ACE) is identical with kininase II, the reduction of its activity by an ACE-inhibitor such as captopril will not only decrease the concentration of angiotensin II but also elevate the levels of kinins. Although the slight increase of the latter will not contribute to the antihypertensive action of ACE-inhibitors, we are sure today that it exhibits local metabolic effects in cardiac and skeletal muscle tissue. These endogenous kinins have been shown to improve the utilisation of glucose in the human forearm, the whole organism and the isolated perfused rat heart and seem to exhibit their effects via prostaglandins. A cross-over plot of the glycolytic intermediates at the height of phosphofructokinase induced by bradykinin in rat heart and the activation of the purified enzyme from rabbit heart by PGE2 point to an enhanced glycolytic rate as their mode of action. From these findings similar effects under ACE-inhibitors can be assumed. This was investigated in ten non-insulin-dependent diabetics, whose glucose disposal rate was measured by the glucose clamp technique. After 25 mg of captopril their peripheral insulin resistance was significantly improved, which was found to be due to an accelerated rate of glucose uptake into their forearm muscle tissue. To evaluate the clinical relevance of these data, 15 mildly hypertensive, overweight type II-diabetic patients (mean age: 53 years; seven women) were hospitalized. After a seven-day wash-out period, the patients were given 25 mg of captopril twice daily for seven days. During the treatment, systemic kinin concentrations significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

[Detection of substrate metabolism in skeletal muscles in the human].

The technical procedure of puncture and catheterization of arteria brachialis and a deep forearm vein in man and practical mode of blood sampling are described. For measurement of local blood flow depending on specific study design, venous occlusion plethysmography, i.m. or i.a. injection of 133Xenon can be used. The theoretical and practical problems of these methods are discussed in detail.

Catheters, Indwelling↗
PubMed1986

[Effect of fructose and sorbitol on insulin-induced hypoglycemia].

Twelve metabolically normal subjects were given 0.325 g/kg fructose or glucose dissolved in water 30 minutes after intravenous infusion of insulin, 0.05 U/kg. Blood glucose concentration was then measured for up to 60 minutes or until the onset of hypoglycaemia (study I). In study II two bread units (BU) were given to six subjects in the form of dark bread, as well as 12 g of butter and water. In two other groups, of six subjects each, 1 BU was substituted either by fructose or sorbitol. Seven subjects who had been given insulin but only water to drink afterwards served as the control group. In study I, both glucose and fructose achieved a clear slowing in the blood-sugar drop compared with the control group. But with glucose there was initially a slight rerise and the final hypoglycaemic level was somewhat delayed. This minor difference between glucose and fructose was not demonstrable in study II with the addition of fat and carbohydrate substitution. Each carbohydrate combination similarly influenced the course of blood sugar concentration. The results indicate that diabetics should continue to be given glucose rather than fructose or sorbitol if hypoglycaemia occurs. On the other hand, both fructose and sorbitol, although acutely less effective in raising blood glucose concentration, do counteract as carbohydrates the development of insulin-induced hypoglycaemia.

Adult↗
PubMed1986

Effects of kallikrein (K), bradykinin (B) and insulin (I), on substrate metabolism in the isolated perfused rat heart.

In the isolated rat heart preparation, perfused at physiological glucose levels, effects of kallikrein (K), bradykinin (B) and insulin (I) on carbohydrate metabolism have been compared. A flow- and I-independent K-effect, obviously working via proteolytic kinin formation, was shown. While I elevated glucose-uptake into the heart preferably via accelerated transport across the membrane and increased rates of glycogen synthesis, B and K significantly activated PFK and reduced myocardial glucose uptake. The latter effect is probably due to an accelerated glycolytic flux leading to decreased G6P-levels and thereby stimulating glycogenolysis. Since aprotinin was able to abolish the K-effect, the latter may possibly be mediated via kinin release.

Animals↗
PubMed1986

Inhibition of muscular glucose uptake by lipid infusion in man.

During a high-dose intravenous infusion of a mixed MCT/LCT-lipid emulsion and a conventional LCT-emulsion respectively, muscle substrate metabolism was investigated using the human forearm technique. With both lipid emulsions, a decrease in fractional muscular glucose extraction was seen, leading to significantly reduced muscular glucose uptake rates. An inverse linear relation between arterial tree fatty acids supply and fractional glucose extraction was seen suggesting that a mechanism according to Randle's glucose fatty acid concept is operating in skeletal muscle in man.

Journal Article↗
PubMed1986

Inhibition of muscular triglyceride lipolysis by ketone bodies: a mechanism for energy-preservation in starvation.

Using the forearm technique, muscle substrate balances were measured in healthy volunteers under the influence of a low dose intraarterial infusion of beta-hydroxybutyrate. The ketone body led to a prompt cessation of muscular release of glycerol and free fatty acids, indicating inhibited muscular triglyceride lipolysis. This finding confirms the concept of substrate regulation of muscle triglyceride lipolysis in vivo.

3-Hydroxybutyric Acid↗
PubMed1986

Improvement of impaired postoperative insulin action by bradykinin.

The effect of bradykinin on insulin-stimulated glucose metabolism was studied in 5 operated patients using the euglycemic insulin clamp technique and the forearm catheter technique. Insulin infusion [1.0 mU/(kg b.w. X min)] raised plasma insulin levels up to 73 muU/ml. Euglycemia was maintained by a computerized glucose infusion rate, amounting to 2.9 mg/(kg b.w. X min). Addition of bradykinin [1.5 micrograms/(kg b.w. X h)] resulted in a significant increase of the glucose infusion rate [+ 1.0 mg/(kg b.w. X min)] indicating elevated whole body glucose uptake. This was related to an enhanced forearm glucose uptake [+ 1.16 mumol/(100 g X min)]. Forearm blood flow remained stable.

Adult↗
PubMed1986

Angiotensin converting enzyme inhibitors in diabetes: experimental and human experience.

Peripheral glucose metabolism was studied during the influence of elevated systemic kinin levels by either application of exogenous bradykinin (BK) or inhibition of endogenous kinin degradation by angiotensin converting enzyme inhibitors (ACEI). In infusion experiments in streptozotocin-diabetic rats, both BK (0.3 micrograms/min) and ACEI (300 micrograms captopril/100 g) showed a significant reduction of elevated blood glucose levels. In man, non-insulin dependent diabetics (NIDD) and healthy subjects in postoperative (POP) stress were examined. Peripheral insulin-sensitivity and muscular glucose balance were determined using the glucose clamp technique and the forearm technique. In NIDD as well as in POP subjects, impaired peripheral insulin responsiveness, as evaluated by whole body glucose consumption, was improved up to 50% by application of BK (80 micrograms/h i.v.) or ACEI (25 mg captopril p.o.), respectively. This was most probably due to accelerated muscular glucose uptake which was assessed in the same experiment and found to be increased 2- to 3-fold under these conditions. As a molecular basis for the observed effects on muscular glucose uptake, phosphofructokinase was found to be markedly stimulated by BK (8 X 10(-10)mol/l) in the isolated perfused rat heart, suggesting accelerated glycolytic flux. It may be concluded that ACEI increase muscular insulin responsiveness, thus being beneficial in insulin-resistant states as well as in hypertension. This metabolic effect is most probably due to elevated systemic kinin levels. Further investigations are required to evaluate the clinical relevance of these findings.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

[Comparative studies of the metabolism of MCT/LCT and LCT emulsions in diabetics].

In 7 moderately overweight non-insulin dependent diabetics with slightly elevated triglyceride levels, disappearance rates of MCT/LCT- und LCT-emulsions were compared. 5 metabolically healthy volunteers served as control. During a 3-hour lipid infusion, serum triglycerides reached a steady state with both emulsions in the healthy controls, whereas in diabetic patients, steady state triglyceride levels were seen only with MCT/LCT. After the end of the lipid infusion, the longest half life value concerning the decline of triglyceride levels was found with LCT in diabetics, while significantly shorter and quite similar half life values were found with LCT in healthy controls and MCT/LCT in diabetics. The shortest half life for serum triglycerides was expectedly found in healthy controls. According to these data, parenteral nutrition with lipids in states of disturbed glucose and lipid metabolism--if necessary--should preferentially be done with MCT/LCT emulsions.

Diabetes Mellitus, Type 2↗
PubMed1985

Evidence for a substrate regulation of triglyceride lipolysis in human skeletal muscle.

Glycerol release from the human forearm which is generally used as a semiquantitative index of intramuscular lipolysis was studied under different hormonal influence and substrate supply in healthy volunteers and juvenile diabetics using the forearm technique. Acute insulin deficiency in juvenile diabetics failed stimulating the rate of muscular lipolysis since the rates of glycerol release in normals and diabetics were the same. In addition, in normal volunteers high physiological levels of insulin caused by an intraarterial infusion of the hormone exhibited no effect on the glycerol release from deep forearm tissue. Similarly, an intraarterial infusion of metaproterenol did not accelerate muscular glycerol release in normal man. However, in juvenile diabetics in acute insulin deficiency the same dose of the catecholamine increased the rate of muscular glycerol production. Elevated substrate supply during intravenous infusion of glucose or fructose yielded increased uptake of glucose and fructose into the deep forearm tissue and thereby promptly blocked muscular glycerol release in normal volunteers and in juvenile diabetics. These findings suggest that the rate of lipolysis in muscle tissue is not primarily under the control of hormones but rather by substrate supply.

Adult↗
PubMed1983

Dose-dependent effect of bradykinin on muscular blood flow and glucose uptake in man.

Using the forearm technique, the effect of bradykinin on muscular blood flow and glucose uptake in healthy man in the postabsorptive state (n = 8) was studied at different doses of an intra-arterial infusion of bradykinin (2.5-150 ng/min). The blood flow of the forearm was increased dose-dependently from basal 2.8 +/- 0.3 up to 14.7 +/- 2.8 ml/(100 g X min). At lower bradykinin concentrations (2.5-25 ng/min), muscular glucose uptake was raised parallel to the increased blood flow from basal 0.71 +/- 0.30 to 2.93 +/- 0.50 mumol/(100 g X min). However, at higher doses (50-150 ng/min) glucose uptake was decreased again. Thus, the greatest metabolic effect of bradykinin was seen at a calculated bradykinin concentration of approximately 1 X 10(-9)M in the blood.

Bradykinin↗
PubMedDate not supplied

Comparison of metabolic clearance rates of MCT/LCT and LCT emulsions in diabetics.

In seven moderately overweight noninsulin-dependent diabetics with slightly elevated triglyceride levels, disappearance rates of infused medium chain triglyceride/long chain triglyceride (MCT/LCT) and long chain triglyceride (LCT) emulsions were compared. Five metabolically healthy volunteers served as controls. During a 3-hr lipid infusion, serum triglycerides reached a steady state with both emulsions in the healthy controls, whereas, in diabetic patients, steady state triglyceride levels were seen only with MCT/LCT. After the end of the lipid infusion, the longest half-life value in the decline of triglyceride levels was found with LCT in diabetics, whereas significantly shorter and quite similar half-life values were found with LCT in healthy controls and with MCT/LCT in diabetics. As expected, the shortest half-life for serum triglycerides was found in healthy controls after MCT/LCT-infusion. Virtually the same differences in serum concentrations and in half-life times were seen with free fatty acids. According to these data, if needed, parenteral nutrition with lipids in states of disturbed glucose and lipid metabolism may preferentially be done with MCT/LCT emulsions.

Blood Glucose↗
PubMedDate not supplied

Changes of hepatic morphology during parenteral nutrition with lipid emulsions containing LCT or MCT/LCT quantified by ultrasound.

Fatty infiltration of the liver with cholestasis is one of the complications of total parenteral nutrition (TPN). The cause has not yet been determined. It seems probable, however, that these alterations could be prevented when a mixture of medium- and long-chain triglycerides (MCT/LCT) is used as a fat component instead of the application of long-chain emulsions (LCT) alone. To determine whether this could also be demonstrated morphologically in man, 14 patients needing TPN (25 kcal/kg BW x day, carbohydrate 45%, fat 35%, protein 20%) were examined by ultrasound in order to compare liver size and gray-scale value before and after 7 days of TPN. Seven of the patients were randomly administered a MCT/LCT emulsion as their fat intake, the other seven were exclusively given LCT. There were no changes in liver size and gray-scale value in the MCT/LCT-group, whereas both parameters showed a significant rise in the patients with LCT (size: 10.4 +/- 1.4 to 11.5 +/- 1.4 cm; gray-scale value: 9.3 +/- 1.0 to 11.6 +/- 0.7). These data suggest that TPN, administered with a mixture of MCT/LCT emulsions as fat components, could reduce the risk of hepatic dysfunction such as cholestasis and fatty infiltration of the liver.

Aged↗