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  • 1
    ISSN: 0196-9781
    Schlagwort(e): Cardiac output ; Free fatty acids ; Glucagon ; Glucose metabolism ; Insulin ; Pulmonary resistance ; Splanchnic blood flow
    Quelle: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 14 (1978), S. 213-222 
    ISSN: 1432-0428
    Schlagwort(e): Body substrate depots ; fuel homeostasis ; physical exercise ; diabetes mellitus ; glucoregulatory hormones ; muscle glycogen ; liver glycogen ; gluconeogenesis ; glycogenolysis ; ketogenesis ; blood glucose ; FFA ; ketone bodies ; amino acids
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary During the initial phase of physical exercise muscle glycogen is the primary source of fuel for contracting muscle in normal man. When exercise continues beyond the first 5–10 min blood glucose and free fatty acids (FFA) become increasingly important substrates. Glucose utilization may account for 25–35% of the total substrate supply during mild to moderately heavy exercise. The augmented glucose utilization by working muscle is balanced by a rise in hepatic glucose production. The latter is achieved primarily by hepatic glycogenolysis during brief work, but during prolonged exercise gluconeogenesis may account for as much as 40–50% of the hepatic glucose output. Muscle uptake of FFA is determined primarily by its availability to the working muscle, and it may account for 30–60% of the total fuel supply. Ketone bodies are not utilized by working muscle in normal man. In patients with diabetes mellitus the metabolic effects of physical exercise are to a large extent determined by the time interval between insulin administration and the onset of exercise. Thus, in insulin treated patients with mild hyperglycaemia and no or minimal ketonaemia the utilization of glycogen, blood glucose and FFA by working muscle is similar to that of healthy subjects, and exercise is accompanied by a fall in blood glucose levels. In contrast, patients with more marked hyperglycaemia and hyperketonaemia may respond to exercise with a further rise in both blood glucose and ketone body levels, reflecting augmented rates of hepatic gluconeogenesis as well as ketogenesis. The repletion of muscle and liver glycogen, which takes place for 24–48 h after exercise, requires — besides carbohydrate feeding — a minimum concentration of insulin. Glycogen resynthesis probably accounts for a major part of the empirically well established beneficial effect of physical exercise in diabetic patients. The above considerations underscore the importance of adequate insulin administration in connection with exercise in diabetic patients.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1432-0428
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary This study was performed in order to test the hypothesis that the connecting peptide of proinsulin, C-peptide, might in itself possess biological activity. Renal tubular Na+, K+-ATPase, which is a well-established target for many peptide hormones, was chosen as a model. Rat C-peptide (I) was found to stimulate Na+, K+-ATPase activity in single, proximal convoluted tubules dissected from rat kidneys. C-peptide increased the Na+ affinity of the enzyme and all subsequent studies were performed at non-saturating Na+ concentrations. C-peptide stimulation of Na+, K+-ATPase activity occurred in a concentration-dependent manner in the dose range 10−8–10−6 mol/l. The presence of neuropeptide Y, 5×10−9 mol/l, enhanced this effect and stimulation of Na+, K+-ATPase activity then occurred in the C-peptide dose range 10−11–10−8 mol/l. C-peptide stimulation of Na+, K+-ATPase activity was abolished in tubules pretreated with pertussis toxin. It was also abolished in the presence of FK 506, a specific inhibitor of the Ca2+-calmodulin-dependent protein phosphatase 2B. These results indicate that C-peptide stimulates Na+, K+-ATPase activity, probably by activating a receptor coupled to a pertussis toxin-sensitive G-protein with subsequent activation of Ca2+-dependent intracellular signalling pathways.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1432-0428
    Schlagwort(e): Key words Gluconeogenesis ; Krebs cycle ; fasting ; insulin-dependent diabetes mellitus ; liver.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Normal subjects, fasted 60 h, and patients with insulin-dependent diabetes mellitus (IDDM), withdrawn from insulin and fasted overnight, were given phenylacetate orally and intravenously infused with [3-14C]lactate and 13C-bicarbonate. Rates of hepatic gluconeogenesis relative to Krebs cycle rates were estimated from the 14C distribution in glutamate from urinary phenylacetylglutamine. Assuming the 13C enrichment of breath CO2 was that of the CO2 fixed by pyruvate, the enrichment to be expected in blood glucose, if all hepatic glucose production had been by gluconeogenesis, was then estimated. That estimate was compared with the actual enrichment in blood glucose, yielding the fraction of glucose production due to gluconeogenesis. Relative rates were similar in the 60-h fasted healthy subjects and the diabetic patients. Conversion of oxaloacetate to phosphoenolpyruvate was two to eight times Krebs cycle flux and decarboxylation of pyruvate to acetyl-CoA, oxidized in the cycle, was less than one-30th the fixation by pyruvate of CO2. Thus, in estimating the contribution of a gluconeogenic substrate to glucose production by measuring the incorporation of label from the labelled substrate into glucose, dilution of label at the level of oxaloacetate is relatively small. Pyruvate cycling was as much as one-half the rate of conversion of pyruvate to oxaloacetate. Glucose and glutamate carbons were derived from oxaloacetate formed by similar pathways if not from a common pool. In the 60-h fasted subjects, over 80 % of glucose production was via gluconeogenesis. In the diabetic subjects the percentages averaged about 45 %. [Diabetologia (1995) 38: 831–838]
    Materialart: Digitale Medien
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  • 5
    ISSN: 1432-0428
    Schlagwort(e): Keywords C-peptide ; active sites ; fragments ; renal tubule segments ; Na + ; K +-ATPase activity.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Proinsulin C-peptide has been shown to stimulate the activity of Na + K + ATPase of rat renal tubule segments. Thirty-six peptides and amino acids, corresponding to parts of the intact rat C-peptide and suitable controls were screened for capacity to stimulate Na +, K +-ATPase in an attempt to determine potential active sites in the C-peptide molecule. The carboxy-terminal tetra and penta peptides were found to elicit 92–103 % of the intact molecule's activity, and the remaining segment, des-(27–31) C-peptide, did not possess stimulatory activity. Peptides from the middle C-peptide segment, however, centering around a GGPEAG sequence, stimulated Na +, K +-ATPase activity (36–80 % of the intact molecule's effect) but this effect was not balanced by corresponding inactivity of other parts. Furthermore, it was paralleled by activity of a non-native dipeptide d-form. It is concluded that the latter effect and that of the middle segment may represent complex interactions other than the apparently specific effects of the C-terminal segment. [Diabetologia (1998) 41: 287–291]
    Materialart: Digitale Medien
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  • 6
    ISSN: 1432-0428
    Schlagwort(e): Keywords Insulin action ; diabetes mellitus ; euglycaemic clamp ; C peptide ; nitric oxide.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Aims. To study the effects of physiological concentrations of rat proinsulin C peptide I and II, respectively, on whole body glucose utilization in streptozotocin diabetic and healthy rats. Methods. A sequential insulin clamp procedure was used (insulin infusion rates 3.0 and 30.0 mU · kg–1· min–1) in awake animals. C-peptide infusion rates were 0.05 and 0.5 nmol · kg–1· min–1. Blood glucose was clamped at 7.7 ± 0.3 mmol/l in the diabetic rats and at 3.9 ± 0.1 mmol/l in the healthy rats. Results. In diabetic rats infused at lower rates of C peptide and insulin, glucose utilization increased by 79–90 % (p 〈 0.001) compared with diabetic animals infused with saline and insulin. Increasing the rate of C-peptide infusion tenfold did not elicit a statistically significant further increase in glucose utilization. C peptide I and II exerted similar effects. The metabolic clearance rate for glucose in the diabetic animals infused with C peptide was not different from that of the healthy rats. During high-dose insulin infusion (30.0 mU · kg–1· min–1) glucose utilization increased considerably and no statistically significant C-peptide effects were observed. About 85 % of the increase in glucose utilization induced by C peptide could be blocked by treatment with N-monomethyl-l-arginine. Conclusions/interpretation. Physiological concentrations of homologous C peptide stimulate whole body glucose utilization in diabetic but not in healthy rats. C peptide I and II elicit similar effects. The influence of C peptide on glucose utilization may be mediated by nitric oxide. [Diabetologia (1999) 42: 958–964]
    Materialart: Digitale Medien
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  • 7
    ISSN: 1432-0428
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
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  • 8
    ISSN: 1432-0428
    Schlagwort(e): Type 1 (insulin-dependent) diabetes ; maximal oxygen uptake ; exercise ; serum triglycerides ; serum cholesterol ; glycaemic control
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary No objective evidence has been presented to support the beneficial effect of physical training on glycaemic control in Type 1 (insulin-dependent) diabetic patients trained two to three times a week for several months. In the present study we examined the possibility that a daily exercise programme would be more suitable for improving glycaemic control. Thirteen patients completed a 5-month study; 6 were randomized to exercise training (20 min daily bicycle exercise) and 7 served as non-exercising controls. The training resulted in an 8% increase in maximal oxygen uptake (p 〈 0.05). No change in glycaemic control occurred during the study period in either group. In addition, serum lipid and lipoprotein levels were followed. Total cholesterol decreased during the study period irrespective of training. No effect was noted on the levels of LDL, VLDL, HDL and HDL2 cholesterol. A significant training effect was obtained in the HDL3 subfraction (−10%,p 〈 0.05). Total triglycerides were unchanged, but a decrease in the level of LDL triglycerides was observed with training (−12%,p 〈 0.01). It is concluded that, in female Type 1 diabetic patients, daily physical training for several months does not improve glycaemic control and results only in minor changes in serum lipoprotein profiles.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-0428
    Schlagwort(e): Glomerular filtration rate ; filtration fraction ; renal blood flow ; glomerular permeability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The possible influence of C-peptide administration on renal function and whole body glucose utilization was examined in 11 patients (Group 1) with Type 1 (insulin-dependent) diabetes mellitus. They were given an i. v. insulin infusion during the night before the study and were euglycaemic at the time of examination. The glomerular filtration rate and effective renal plasma flow were measured by clearance techniques using constant-rate infusions of inulin and sodium para-aminohippurate. After baseline measurements C-peptide was infused during two periods of 60 min at rates of 5 and 30 pmol·kg−1·min−1. In a control study 0.9% NaCl was infused during two 60 min periods in ten Type 1 diabetic patients (Group 2), Glomerular filtration rate decreased by 7%(p〈0.001), effective renal plasma flow increased by 3%, (p〈0.05) and whole-body glucose utilization rose by approximately 25%(p〈0.05) above basal during low-dose C-peptide infusion. Group 2 showed an unaltered glomerular filtration rate, effective renal plasma flow and glucose utilization during 60 min of NaCl infusion. The differences between Group 1 and Group 2 in glomerular filtration rate and glucose utilization were statistically significant. It is concluded that short-term administration of C-peptide in physiological amounts to patients with Type 1 diabetes may reduce the glomerular filtration rate and increase whole-body glucose utilization. The results suggest the possibility that short-term C-peptide administration may exert a regulatory influence on renal function and stimulate glucose utilization in Type 1 diabetic patients.
    Materialart: Digitale Medien
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 39 (1996), S. 687-695 
    ISSN: 1432-0428
    Schlagwort(e): Acceleration index ; brake index ; expiration-inspiration ratio ; diabetic polyneuropathy ; nerve conduction velocity ; quantitative somatosensory thresholds ; vibrametry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In order to determine the possible influence of C-peptide on nerve function, 12 insulin-dependent diabetic (IDDM) patients with symptoms of diabetic polyneuropathy were studied twice under euglycaemic conditions. Tests of autonomic nerve function (respiratory heart rate variability, acceleration and brake index during tilting), quantitative sensory threshold determinations, nerve conduction studies and clinical neurological examination were carried out before and during a 3-h i. v. infusion of either C-peptide (6 pmol · kg−1 · min−1) or physiological saline solution in a double-blind study. Plasma C-peptide concentrations increased from 0.11±0.02 to 1.73±0.04 nmol/l during C-peptide infusion. Clinical neurological examination quantitative sensory threshold evaluations and nerve conduction measurements failed to detect significant changes between C-peptide and saline study periods. Respiratory heart rate variability increased significantly from 13±1 to 20±2% during C-peptide infusion (p〈0.001), reaching normal values in five of the subjects; control studies with saline infusion did not alter the heart rate variability (basal, 14±2; saline, 15±2%). A reduced brake index value was found in seven patients and increased significantly during the C-peptide infusion period (4.6±1.0 to 10.3±2.2%, p〈0.05) but not during saline infusion (5.9±2 to 4.1±1.1%, NS). It is concluded that short-term (3-h) infusion of C-peptide in physiological amounts may improve autonomic nerve function in patients with IDDM.
    Materialart: Digitale Medien
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