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  • 1
    Electronic Resource
    Electronic Resource
    Physical exercise and fuel homeostasis in diabetes mellitus (1978)
    Springer
    Diabetologia 14 (1978), S. 213-222 
    Details
    ISSN: 1432-0428
    Keywords: 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
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01219419
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of C-peptide on blood flow, capillary diffusion capacity and glucose utilization in the exercising forearm of Type 1 (insulin-dependent) diabetic patients (1992)
    Springer
    Diabetologia 35 (1992), S. 1151-1158 
    Details
    ISSN: 1432-0428
    Keywords: Hand ergometer ; indicator-diffusion technique ; lactate exchange ; oxygen uptake ; skeletal muscle ; substrate exchange ; vascular resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Microvascular dysfunction is frequently seen in patients with Type 1 (insulin-dependent) diabetes. The present study was undertaken to examine whether skeletal muscle microcirculation in Type 1 diabetic patients is influenced by C-peptide. Forearm blood flow, capillary diffusion capacity and substrate exchange were studied during strenuous rhythmic forearm exercise on a hand ergometer. Measurements were made before and during i.v. infusion for 60 min of C-peptide or 0.9% NaCl in Type 1 diabetic patients and healthy subjects. During infusion the C-peptide levels in the diabetic patients increased from less than 0.05 nmol/l to 1.32±0.08 nmol/l. Prior to infusion forearm blood flow and capillary diffusion capacity during exercise were lower in the diabetic patients than the control subjects. During C-peptide infusion both variables increased in the diabetic patients (blood flow +27±4%, capillary diffusion capacity +52±9%) to levels similar to those in the healthy subjects, while no significant change was seen in the healthy control subjects or the diabetic patients given NaCl. Forearm uptake of oxygen and glucose in the diabetic patients increased markedly after C-peptide administration but were unchanged after NaCl infusion. Significant uptake of C-peptide to the deep forearm tissues was observed in the resting state; approximately 7±2% of the arterial C-peptide concentration was extracted by forearm tissues in diabetic patients as well as in healthy control subjects. It is concluded that replacement of C-peptide to physiological levels in young Type 1 diabetic patients results in a normalization of both blood flow and capillary diffusion capacity during exercise, as well as augmented uptake of oxygen and glucose by exercising muscle. The findings suggest that C-peptide may be of importance for microvascular function in exercising muscle in Type 1 diabetes. Finally, skeletal muscle is a major site of C-peptide disposal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401369
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  • 3
    Electronic Resource
    Electronic Resource
    Renal and splanchnic exchange of human biosynthetic C-peptide in Type 1 (insulin-dependent) diabetes mellitus (1991)
    Springer
    Diabetologia 34 (1991), S. 423-428 
    Details
    ISSN: 1432-0428
    Keywords: Glucose utilization ; Type 1 (insulin-dependent) diabetes mellitus ; human C-peptide ; glucagon ; renal uptake ; hepatic uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Biosynthetic human C-peptide or NaCl (154 mmol·l−1) was given intravenously to 13 Type 1 (insulin-dependent) diabetic patients to determine the renal and splanchnic exchange of C-peptide. Catheters were inserted percutaneously into an artery and a renal and hepatic vein. Infusions of C-peptide were given for 60 min at two dose levels (5 and 30 pmol·kg−1·min−1). Insulin was infused throughout the study (0.5 mU·kg−1·min−1) and plasma glucose was kept constant by a variable glucose infusion. The regional blood flows were measured by indicator dilution techniques. In 11 of the 13 patients basal C-peptide levels were not detectable. The arterial steady-state C-peptide concentration was 0.81±0.10 nmol·l−1 and 2.33±0.30 nmol·l−1 at the low and high rate infusions, respectively. Renal uptake was 124±18 pmol·min−1 at the low infusion corresponding to 39% of the infused amount. At the higher dose C-peptide infusion renal uptake increased to 155±21 pmol·min−1 (p〈0.05). Urinary excretion of C-peptide was 7±2 pmol·min−1 at the low dose infusion and increased to 34±6 pmol·min−1 at the high dose infusion (p〈0.01). The proportions of infused amount excreted were fairly constant and between 2% and 3%. No net exchange of C-peptide was found across the splanchnic vascular bed. The rate of glucose infusion had to be increased by 35% during the low dose C-peptide, but not during NaCl infusion in order to maintain a constant plasma glucose concentration. Arterial plasma concentrations of noradrenaline increased by 15–25% during both C-peptide and NaCl infusions. It is concluded that in patients with Type 1 diabetes (a) the kidney is the primary site of C-peptide removal, (b) renal metabolism rather than urinary excretion is the dominating process for C-peptide elimination (c) the excreted proportions of an infused amount of C-peptide were fairly constant between 2% and 3% and (d) no hepatic C-peptide catabolism could be detected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403181
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  • 4
    Electronic Resource
    Electronic Resource
    C-peptide improves autonomic nerve function in IDDM patients (1996)
    Springer
    Diabetologia 39 (1996), S. 687-695 
    Details
    ISSN: 1432-0428
    Keywords: Acceleration index ; brake index ; expiration-inspiration ratio ; diabetic polyneuropathy ; nerve conduction velocity ; quantitative somatosensory thresholds ; vibrametry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00418540
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  • 5
    Electronic Resource
    Electronic Resource
    Rat C peptide I and II stimulate glucose utilization in STZ-induced diabetic rats (1999)
    Springer
    Diabetologia 42 (1999), S. 958-964 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin action ; diabetes mellitus ; euglycaemic clamp ; C peptide ; nitric oxide.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051254
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  • 6
    Electronic Resource
    Electronic Resource
    Brain substrate utilisation during acute hypoglycaemia (1999)
    Springer
    Diabetologia 42 (1999), S. 812-818 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Amino acids ; normal subjects ; jugular vein ; lactate ; pyruvate ; β-hydroxybutyrate.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Our study was undertaken to examine directly the utilisation of glucose and alternative substrates, in particular amino acids, during hypoglycaemia. Methods. Catheters were positioned in the jugular venous bulb and an artery in six healthy subjects in the overnight fasted state. Arterio-venous differences for glucose, amino acids, lactate and pyruvate were measured in the basal state, during hyperinsulinaemic euglycaemia and during hyperinsulinaemic hypoglycaemia. The subjects were studied on two different occasions, once during intravenous infusion of amino acids and once during infusion of saline. Results. In the basal state the fractional extraction of glucose across the brain was 10 ± 2 %, glucose uptake accounted for 106 ± 5 % of the brain's oxidative metabolism. There was a small release of lactate and pyruvate. During hyperinsulinaemia glucose uptake continued to account for the entire fuel requirement of the brain. Hyperaminoacidaemia did not result in net amino acid uptake by the brain. During hypoglycaemia (2.4 ± 0.2 mmol/l) fractional extraction of glucose by the brain increased (p 〈 0.01) and glucose uptake accounted for 90 ± 15 % of the brain's oxidative metabolism. Uptake of amino acids, lactate or pyruvate could not be detected. Conclusion/interpretation. 1) Brain fractional extraction of glucose increases during hypoglycaemia, 2) hyperinsulinaemia does not change fractional extraction of glucose by the brain, 3) augmented availability of amino acids does not result in brain amino acid uptake during euglycaemia or hypoglycaemia and 4) under the present study conditions glucose remains the major substrate for cerebral metabolism during hypoglycaemia; lactate or pyruvate uptake by the brain can not be detected. [Diabetologia (1999) 42: 812–818]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051231
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  • 7
    Electronic Resource
    Electronic Resource
    Normalization of hepatic glucose regulation despite systemic insulin delivery. Studies in patients with pancreatic transplantation for Type 1 (insulin-dependent) diabetes mellitus (1991)
    Springer
    Diabetologia 34 (1991), S. 345-349 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; pancreatic transplantation ; hepatic glucose regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary With current surgical techniques for pancreatic transplantation, the graft is anastomosed to the iliac vessels, resulting in delivery of insulin to the systemic circulation rather than to the portal vein as in healthy man. The possible influence of the altered route of insulin delivery on the regulation of splanchnic glucose metabolism was studied in four patients with Type 1 (insulin-dependent) diabetes mellitus at 6–19 months after combined pancreatic and kidney transplantation. Four non-diabetic, age-matched renal transplant recipients and two groups of age-matched healthy subjects served as controls. The studies were carried out in the basal state and during two rates of intravenous glucose infusion (2 and 4 mg · kg−1 · min−1). Fasting arterial glucose and splanchnic glucose output was similar in all groups. Basal hyperinsulinaemia was present in pancreatic graft recipients compared to healthy subjects. During low rate intravenous glucose infusion splanchnic glucose output decreased to a similar extent in all groups. With the higher glucose infusion rate (4 mg · kg−1 · min−1) a net glucose uptake was observed which was similar in all three groups. Peripheral glucose uptake was unchanged at the lower glucose infusion rate but increased by 45–55% at the higher rate. It is concluded that despite systemic insulin delivery from a heterotopic pancreatic graft, hepatic glucose metabolism appears normal both in the post-absorptive state and in response to glucose-stimulated endogenous insulin secretion. Portal insulin delivery is thus not necessary for normal hepatic glucose metabolism in the Type 1 diabetic patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00405007
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  • 8
    Electronic Resource
    Electronic Resource
    Does C-peptide have a physiological role? (1994)
    Springer
    Diabetologia 37 (1994), S. S99 
    Details
    ISSN: 1432-0428
    Keywords: Blood-retinal barrier function ; capillary diffusion capacity ; glucose utilization ; kidney function ; insulin-dependent diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Short-term administration of physiological amounts of C-peptide to patients with insulin-dependent diabetes was found to reduce the glomerular hyperfiltration in these patients as well as augment whole body glucose utilization. It could also be shown that C-peptide administration increases blood flow, oxygen uptake and capillary diffusion capacity of exercising forearm muscle in IDDM patients, probably by increasing capillary recruitment in the working muscle. Studies under in vitro conditions have shown that C-peptide stimulates glucose transport in skeletal muscle with its maximal effect within the physiological concentration range. The findings in a clinical study in which IDDM patients were given C-peptide and insulin or insulin alone for 4 weeks in a double-blind randomized study design, indicate that C-peptide improves renal function by reducing urinary albumin excretion and glomerular filtration, decreases blood retinal barrier leakage and improves metabolic control. Preliminary findings suggest that C-peptide administration on a short-term basis (3 h) may ameliorate autonomic neuropathy by restoring to near normal the heart rate variability in response to expiration and inspiration. Insight into a possible mechanism of action of C-peptide is provided by the finding that C-peptide stimulates Na+K+-ATPase activity in renal tubular segments. In conclusion, the present results suggest that, contrary to the prevailing view, C-peptide possesses important physiological effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400832
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  • 9
    Electronic Resource
    Electronic Resource
    Estimates of Krebs cycle activity and contributions of gluconeogenesis to hepatic glucose production in fasting healthy subjects and IDDM patients (1995)
    Springer
    Diabetologia 38 (1995), S. 831-838 
    Details
    ISSN: 1432-0428
    Keywords: Key words Gluconeogenesis ; Krebs cycle ; fasting ; insulin-dependent diabetes mellitus ; liver.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050360
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  • 10
    Electronic Resource
    Electronic Resource
    Fourth meeting of the Scandinavian Society for the Study of Diabetes Stockholm, February 1–3, 1968 Abstracts (1968)
    Springer
    Diabetologia 4 (1968), S. 309-315 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01309907
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