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  • 1
    Electronic Resource
    Electronic Resource
    INTERACTION OF LEUCINE, GLUCOSE, AND KETONE METABOLISM IN RAT BRAIN IN VITRO (1979)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 32 (1979), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Brain cortex slices from fed, 48 h and 120 h fasted rats were incubated and 14CO2 was measured from (a) [U-14C]glucose (5 mm) either alone or in the presence of l-lcucine (0.1 or 1 mm), and (b) [U-14C]leucine or [l-14C]leucine at 0.1 or 1 mm with or without glucose (5 mm). In other experiments, sodium dl-3-hydroxybutyrate (3-OHB) or acetoacetate (AcAc) at 1 or 5 mm were added in the above incubation mixture. The rate of conversion of [U14C]glucose to CO2 was decreased 20% by leucine at 1 mm and 30–50% by 3-OHB at 1 or 5 mm but not by leucine at 0.1 mm. The effects of 3-OHB and of leucine (1 mm) were not additive. The effects of leucine were similar in the fed and fasted rats. The rate of conversion of [U-14C]leucine or [l-,4C]leucine to 14CO2 at 0.1 mm and 1.0 mm was increased by glucose (35%) in the fed or fasted rats. Ketone bodies in the absence of glucose had no effect on leucine oxidation. However, the stimulatory effect of glucose on the rate of conversion of leucine to CO2 was inhibited by 3-OHB at 5 mm. These results suggest that (a) leucine in increased concentrations (1 mm) may reduce glucose oxidation by brain cortex while itself becoming an oxidative fuel for brain, and (b) leucine oxidation by brain may be influenced by the prevailing glucose and ketone concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1979.tb04510.x
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  • 2
    Electronic Resource
    Electronic Resource
    Cyclosporin reduces renal prostanoid excretion in type 1 diabetic patients (1992)
    Springer
    Acta diabetologica 29 (1992), S. 1-5 
    Details
    ISSN: 1432-5233
    Keywords: Cyclosporin ; Diabetes ; Prostanoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prostacyclin and thromboxane A2 are important regulators of kidney blood flow. To examine whether changes in their metabolism could be involved in the nephrotoxicity of cyclosporin, we determined urinary excretion of 6-keto PGF1a and dinor-6-keto PGF1a (prostacyclin metabolites) and dinor-TxB2 (thromboxane metabolite) in five newly diagnosed type 1 diabetic patients during and after stopping cyclosporin therapy. In the resting state, cyclosporin had no effect on prostanoid excretion. In response to exercise, urinary excretion of 6-keto PGF1a was reduced by 50% (P〈0.02), dinor-6-keto PGF1a by 15% (P〈0.05) and dinor-TxB2 by 45% (P〈0.02), while albumin excretion increased 4.5-fold (P〈0.05) during cyclosporin therapy. Simultaneously, there was a rise in serum creatinine concentration, and renal biopsy specimens obtained from three patients showed periglomerular and interstitial fibrosis and tubular atrophy. After the discontinuation of cyclosporin therapy, serum creatinine concentrations returned to normal, histological changes improved and there was an associated rise in urinary prostanoid excretion. These data suggest that a reduction in renal prostanoid synthesis by cyclosporin may diminish renal blood flow and function, and lead to histological changes in the kidney.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00572820
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  • 3
    Electronic Resource
    Electronic Resource
    Occurrence and interrelationships of complications in insulin-dependent diabetes in Finland (1997)
    Springer
    Acta diabetologica 34 (1997), S. 33-38 
    Details
    ISSN: 1432-5233
    Keywords: Key words Insulin-dependent diabetes ; Nephropathy ; Neuropathy ; Retinopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the study was to examine the prevalence and interrelationships of micro- and macrovascular complications and their risk factors in insulin-dependent (type 1) diabetic patients. The prevalence of nephropathy, retinopathy and cardiovascular disease was examined, and their associations to risk factors (glycemic control, blood pressure, blood lipid concentrations) and neuropathy were estimated in a cross-sectional study. A total of 140 type 1 diabetic patients were examined. They were grouped by gender, age, and duration of diabetes into 14 subgroups of 10 patients each. Nephropathy was observed in 40%, retinopathy in 55%, and signs of cardiovascular disease in less than 5% of patients. Microvascular complications were associated with the duration of diabetes, systolic blood pressure, and serum triglyceride concentration. The glycosylated hemoglobin (HbA1c) level was significantly associated with the presence of nephropathy, whereas the association with retinopathy was of borderline significance. Statistically speaking, the duration of diabetes, mean systolic blood pressure, HbA1c, and triglyceride level explained 31% of the variation in log albumin excretion rate (P〈0.001). Duration, age, and triglyceride level explained 46% of the variation in the severity of retinopathy (P〈0.001) and 31% of the variation in the vibration perception threshold in the ankle (P〈0.001). While the well-established risk factors (duration of diabetes, hyperglycemia, and hypertension) are associated with microvascular complications, more than half of the variation in their severity cannot be explained. An additional risk factor may involve triglycerides even at a normal serum concentration. The mechanism could be the incorporation of triglycerides in the cell membrane, leading to variations in membrane fluidity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005920050062
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  • 4
    Electronic Resource
    Electronic Resource
    Lipids in the pulmonary artery and the lungs of severely diabetic rats (1977)
    Springer
    Diabetologia 13 (1977), S. 305-310 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes ; non-esterified fatty acids ; lipid metabolism ; lung ; phospholipids ; pulmonary artery ; rat ; streptozotocin ; triglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the effect of diabetes on the lipid composition of the lungs and of the pulmonary artery, 43 streptozotocin diabetic rats and 43 control rats were examined. Triglyceride deposits were observed by a histochemical method in the branches of the pulmonary artery in 10 diabetic rats but in none of the controls. In the pulmonary tissue of the diabetic rats the total lipid content was not different from that of control animals, but the relative amount of phospholipids was decreased (p〈0.001), and that of non-esterified fatty acids (p〈0.001) and triglycerides (p〈0.05) increased as compared to the control rats. These results indicate abnormalities in the lipid metabolism of the pulmonary artery and lungs during insulin deficiency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01223270
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  • 5
    Electronic Resource
    Electronic Resource
    Response of adipose tissue lipoprotein lipase activity and serum lipoproteins to acute hyperinsulinaemia in man (1984)
    Springer
    Diabetologia 27 (1984), S. 364-369 
    Details
    ISSN: 1432-0428
    Keywords: Adipose tissue lipoprotein lipase ; insulin ; glucose ; insulin sensitivity ; lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to assess the short-term effects of hyperinsulinaemia and hyperglycaemia on adipose tissue lipoprotein lipase activity and on serum lipoproteins, we measured these variables in ten normal subjects during euglycaemic and hyperglycaemic hyperinsulinaemic clamps. The mean steady-state plasma glucose and insulin concentrations, respectively, were 4.7 mmol/l and 101 mU/l during euglycaemic moderate-insulin clamp, 4.9 mmol/l and 565 mU/l during euglycaemic high-insulin clamp, and 8.8 mmol/l and 148 mU/l during hyperglycaemic clamp. Saline infusion was used as control. The adipose tissue lipoprotein lipase activity rose significantly over 5 h during high-insulin clamp (p〈0.01) and during hyperglycaemic clamp (p〈0.05), but did not change during the moderate-insulin clamp. The magnitude of change of lipoprotein lipase activity from baseline (either rise or fall) was inversely related to the preclamp activity during euglycaemic moderate-insulin clamp (r= -0.67), during hyperglycaemic clamp (r= -0.68) and during infusion of saline (r= -0.75, p〈0.05). Total serum triglyceride concentration decreased significantly during all clamp studies compared with the control experiment. This change was mainly accounted for by a decrease of VLDL triglyceride. The LDL cholesterol level fell by an average of 5% (p〈0.05) during the high-insulin clamp and by 10% (p〈0.05) during the hyperglycaemic clamp. The HDL cholesterol level did not change significantly. It is concluded that adipose tissue lipoprotein lipase activity in man is increased by physiological insulin levels during hyperglycaemia and also by supraphysiological insulin levels during euglycaemia, but is not influenced by physiological hyperinsulinaemia without hyperglycaemia. Low basal lipoprotein lipase activity is more sensitive to insulin-glucose stimulation than primarily high lipoprotein lipase activity. Acute hyperinsulinaemia decreases VLDL triglyceride and LDL cholesterol concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00304851
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  • 6
    Electronic Resource
    Electronic Resource
    The adjustment of diet and insulin dose during long-term endurance exercise in Type 1 (insulin-dependent) diabetic men (1988)
    Springer
    Diabetologia 31 (1988), S. 35-40 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes ; exercise ; insulin dose ; diet ; insulin sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We examined in 2 consecutive years the effect of a 75-km (〉7 h) cross country skiing on dietary and insulin requirements and glycaemic control in 9 Type 1 (insulin-dependent) diabetic patients. In the first year, the patients were hyperglycaemic (20.9±1.8 mmol/l) before the race due to excessive carbohydrate loading (65 g) and reduction (by 58%) of short-acting insulin for breakfast. In the second year, breakfast included less carbohydrate (40 g) and more protein, and the morning short-acting insulin was reduced by 35%. With this adjustment of therapy the pre-exercise hyperglycaemia was less (p〈0.05). The morning intermediate-acting insulin was reduced by 28 and 38% in consecutive years. During both races carbohydrate intake approximated 40 g/h, and blood glucose was maintained at near normal levels after 33 km of skiing. Hypoglycaemia did not occur during exercise, but one patient had symptomatic hypoglycaemia after finishing the second race. The day after exercise insulin sensitivity was increased in all four patients studied. Insulin treated patients can perform strenuous long-term exercise and maintain near normoglycaemia with a proper adjustment of therapy. Augmented insulin sensitivity may contribute to post-exercise hypoglycaemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00279130
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  • 7
    Electronic Resource
    Electronic Resource
    Follow-up of cyclosporin A treatment in Type 1 (insulin-dependent) diabetes mellitus: lack of long-term effects (1991)
    Springer
    Diabetologia 34 (1991), S. 429-434 
    Details
    ISSN: 1432-0428
    Keywords: Cyclosporin A ; Type 1 (insulin-dependent) diabetes mellitus ; immunotherapy ; C-peptide ; islet function ; remission of Type 1 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the Canadian/European randomized controlled study on cyclosporin A (CsA) in recent onset Type 1 (insulin-dependent) diabetes, treatment with the immunosuppressive drug had increased and maintained Beta-cell function and clinical remission during the first 12 months. Following discontinuation of the study drug and double-blinding after a mean of 13.8 months former CsA patients doubled the daily insulin dose within 6 months reaching the level of former placebo patients. The difference in Beta-cell function between the two groups was also lost. Metabolic control (HbA1c) was transiently worse in the former CsA group. Adverse effects of cyclosporin A on systolic blood pressure, haemoglobin levels, serum potassium and creatinine levels also remitted during that time. We conclude that treatment with cyclosporin A for a mean of 13.8 months had no long-lasting effect on the course of Type 1 diabetes persisting beyond drug discontinuation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403182
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  • 8
    Electronic Resource
    Electronic Resource
    Non-esterified fatty acids regulate lipid and glucose oxidation and glycogen synthesis in healthy man (1994)
    Springer
    Diabetologia 37 (1994), S. 202-209 
    Details
    ISSN: 1432-0428
    Keywords: Key words Fatty acid metabolism, insulin sensitivity, glycogen, glycogen synthase, lipoproteins.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We examined the interrelationship of lipid and glucose metabolism in the basal state and during insulin stimulus in 19 healthy men (27±2 years, body mass index 23.6±0.6 kg/m2). In each subject, we performed a 4-h euglycaemic (5.3±0.1 mmol/l) hyperinsulinaemic (647±21 pmol/l) insulin clamp with indirect calorimetry in the basal state and during insulin infusion, and muscle biopsies before and at the end of the clamp. In the basal state, serum non-esterified fatty acid levels correlated directly with lipid oxidation (r =0.56, p〈0.05) and indirectly with glucose oxidation (r = –0.80, p〈0.001). Lipid and glucose oxidation rates were inversely related in the basal state (r = –0.47, p〈0.05) and during insulin infusion (r = –0.65, p〈0.01). Basal lipid oxidation and glycogen synthase total activity correlated inversely (r = –0.54, p〈0.05). Lipid oxidation both in the basal state (r = –0.61, p〈0.01) and during insulin infusion (r = –0.62, p〈0.05) was inversely related to muscle glycogen content after the insulin clamp. Fasting plasma triglyceride concentration correlated directly to fasting insulin (r =0.55, p〈0.05) and C-peptide (r =0.50, p〈0.03) concentrations and inversely to non-oxidative glucose disposal rate at the end of clamp (r = –0.54, p〈0.05). In conclusion: 1) Serum non-esterified fatty acid concentration enhances lipid and reduces glucose oxidation. 2) Lipid oxidation is inversely related to total glycogen synthase activity. 3) Lipid oxidation both in the basal state and during insulin stimulus correlates inversely with muscle glycogen content after insulin infusion. 4) Even in normotriglyceridaemic subjects, plasma triglycerides reduce insulin-stimulated non-oxidative glucose disposal. These data suggest that serum non-esterified fatty acids in physiologic concentrations have an important role in the regulation of lipid and glucose oxidation as well as glucose storage as glycogen. [Diabetologia (1994) 37: 202–209]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050094
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  • 9
    Electronic Resource
    Electronic Resource
    Intramuscular triglyceride content is increased in IDDM (1998)
    Springer
    Diabetologia 41 (1998), S. 111-115 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Type 1 diabetes ; muscle ; triglycerides ; insulin sensitivity ; lipid oxidation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Increased lipid oxidation is related to insulin resistance. Some of the enhanced lipid utilization may be derived from intramuscular sources. We studied muscle triglyceride (mTG) concentration and its relationship to insulin sensitivity in 10 healthy men (age 29 ± 2 years, BMI 23.3 ± 0.6 kg/m2) and 17 men with insulin-dependent diabetes mellitus (IDDM) (age 30 ± 2 years, BMI 22.8 ± 0.5 kg/m2, diabetes duration 14 ± 2 years, HbA1 c 7.7 ± 0.3 %, insulin dose 48 ± 3 U/day). Insulin sensitivity was measured with a 4 h euglycaemic (5 mmol/l) hyperinsulinaemic (1.5 mU or 9 pmol · kg–1· min–1) clamp accompanied by indirect calorimetry before and at the end of the insulin infusion. A percutaneous biopsy was performed from m. vastus lateralis for the determination of mTG. At baseline the IDDM patients had higher glucose (10.2 ± 0.9 vs 5.6 ± 0.1 mmol/l, p 〈 0.001), insulin (40.3 ± 3.2 vs 23.2 ± 4.2 pmol/l, p 〈 0.01), HDL cholesterol (1.28 ± 0.06 vs 1.04 ± 0.03 mmol/l, p 〈 0.01) and mTG (32.9 ± 4.6 vs 13.6 ± 2.7 mmol/kg dry weight, p 〈 0.01) concentrations than the healthy men, respectively. The IDDM patients had lower insulin stimulated whole body total (–25 %, p 〈 0.001), oxidative (–18 %, p 〈 0.01) and non-oxidative glucose disposal rates (–43 %, p 〈 0.001), whereas lipid oxidation rate was higher in the basal state ( + 44 %, p 〈 0.01) and during hyperinsulinaemia ( + 283 %, p 〈 0.05). mTG concentrations did not change significantly during the clamp or correlate with insulin stimulated glucose disposal. In healthy men mTG correlated positively with lipid oxidation rate at the end of hyperinsulinaemia (r = 0.75, p 〈 0.05). In conclusion: 1) IDDM is associated with increased intramuscular TG content. 2) mTG content does not correlate with insulin sensitivity in healthy subjects or patients with IDDM. [Diabetologia (1998) 41: 111–115]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050875
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  • 10
    Electronic Resource
    Electronic Resource
    Influence of norepinephrine and exercise on lipolysis in adipose tissue of diabetic rats (1975)
    Springer
    Diabetologia 11 (1975), S. 401-405 
    Details
    ISSN: 1432-0428
    Keywords: Adipose tissue ; catecholamines ; diabetes ; exercise ; free fatty acids ; glycerol ; lipolysis ; rat ; streptozotocin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The lipolytic effect of norepinephrine (NE) in adipose tissue in vitro was studied before and after exercise in non-fasted rats with severe, untreated streptozotocin diabetes. It was observed that: 1. NE in increasing concentrations stimulated glycerol release in vitro to an equal extent from the adipose tissue of nondiabetic and diabetic rats. However, the re-esterification of free fatty acids (FFA) in adipose tissue in vitro was decreased by NE in diabetic rats as compared to normal rats. 2. During exercise NE further decreased the re-esterification of FFA in vitro in adipose tissue of diabetic rats. 3. Exercise did not change NE-induced glycerol release in vitro in the adipose tissue of diabetic rats. 4. In diabetic animals the increase in plasma glycerol and FFA during exercise was correlated inversely with the NE-induced release of glycerol and FFA from the adipose tissue of the same animals after exercise. The lipolytic effect of NE is not significantly different in adipose tissue of diabetic and nondiabetic rats. By decreasing the re-esterification of FFA in vitro, NE is probably responsible for the observed increase in the release of FFA in vivo, a likely energy source in severely diabetic animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00429907
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