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Biomedical subjects

V A Koivisto

Publications and source records attributed to V A Koivisto.

At least 163 records · Page 9Linked to original sources

Increased insulin binding to monocytes after acute exercise in normal man.

The effect of exercise on 125I-insulin binding to monocytes was studied in 10 healthy subjects. We found that acute exercise (bicycle ergometer for 3 h) led to a significant increase (36%) in insulin binding to monocytes, which returned to basal levels by 24 h after exercise. The changes in insulin binding were mainly due to an increase in receptor affinity. The increase in insulin binding during exercise correlated with the fall in plasma glucose but not with the decrease in plasma insulin or increase in blood ketones. We conclude that acute exercise increases insulin binding which may contribute to augmented insulin sensitivity associated with exercise.

Adult↗

Lipids in the pulmonary artery and the lungs of severely diabetic rats. A histochemical and chemical study.

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 less than 0.001), and that of non-esterified fatty acids (p less than 0.001) and triglycerides (p less than 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.

Animals↗

HLA antigens in patients with juvenile diabetes mellitus, coeliac disease and both of the diseases.

We determined the prevalence of 24 antigens controlled by the HLA-A and B loci in twenty patients with juvenile diabetes mellitus (JDM), in twenty patients with coeliac disease (CD), and in eight patients with both of these diseases. The prevalence of HLA-B8 was increased in JDM chi2 = 12.52, p = 0.00040) and in CD (chi2 = 26.47, p less than 0.000001) as compared to 900 controls. There was only a modest increase of Bw15 in JDM (chi2 = 8.86, p = 0.0029) and in patients with both diseases (chi2 = 2.72). The observed prevalence of phenotype HLA-B8, Bw15 was enhanced in JDM (chi2 = 16.03, p = 0;000063) and in patients with both JDM and CD (chi2 = 24.48, p = 0.00000074) as compared with controls. In the latter group the observed value was 2.2 fold to that expected. In family studies the children having both B8 and Bw15 were more disposed to develop diabetes than siblings with only one of these antigens. In conclusion, the inherited susceptibility to develop juvenile diabetes is markedly associated with HLA-B8 and slightly with HLA-Bw15, and that of coeliac disease with HLA-B8 in Finnish paediatric patients. The presence of both B8 and Bw15 simultaneously increases the susceptibility to have both JDM and CD.

Adolescent↗

Metabolic and hormonal effects of exercise in mild streptozotocin diabetes.

Metabolic and hormonal changes produced by muscular exercise were studied in rats with mild streptozotocin diabetes. In both diabetic and control animals the mean blood glucose increased and liver glycogen decreased during exercise. The postexercise blood glucose level correlated with the liver glycogen content in diabetic rats. A decrease of blood glucose occurred in some diabetic animals, and these also showed a decrease of liver glycogen to very low levels during exercise. During exercise the rise of plasma glycerol was higher in diabetic than in control animals, but changes in circulating free fatty acids, acetone bodies, insulin, corticosterone, lactate, and acid-base equilibrium were similar in the two groups. The results indicate that the only abnormal metabolic response to exercise in rats with mild diabetes is a slight increase of lipid mobilization.

Animals↗

Intracellular enzymes of collagen biosynthesis in rat kidney in streptozotocin diabetes.

The activities of the four enzymes catalyzing intracellular post-translational modifications of the collagen polypeptide chains were assayed in the kidneys of rats with streptozotocin diabetes. When the changes in the four enzyme activities were expressed per milligram of protein in the 15,000 X g supernatant of the kidney homogenates, there were no changes in any of the enzyme activities at four weeks and only slight increases in the prolyl and lysyl hydroxylase activities at 12 weeks after the induction of diabetes. When the changes were expressed as total enzyme activities per two kidneys, again no changes were found in any enzyme activity at four weeks, but at 12 weeks significant increases were found in all four enzyme activities, namely prolyl hydroxylase, lysyl hydroxylase, collagen galactosyltransferase, and collagen glucosyltransferase. The data would be consistent with an increased collagen synthesis in diabetic kidneys, but they do not support the hypothesis that there might be specific changes in some of these enzyme activities or in the level of certain posttranslational modifications of the collagen polypeptide chains in this disease.

Animals↗

Influence of norepinephrine and exercise on lipolysis in adipose tissue of diabetic rats.

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.

Adipose Tissue↗

Subcutaneous adipose tissue expression of plasminogen activator inhibitor-1 (PAI-1) in nondiabetic and Type 2 diabetic subjects.

OBJECTIVE: Increased plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been suggested to be a part of the insulin resistance syndrome, and recent data suggest that adipose tissue participates in the production of PAI-1. We examined the expression and insulin regulation of subcutaneous adipose tissue PAI-1 mRNA and its relationship to insulin sensitivity. DESIGN: A cross-sectional study involving five lean (60.0+/-3.1 years, BMI 23.5+/-0.5 kg/m(2)) and six obese nondiabetic men (56.0+/-3.1 years, BMI 30.4+/-0.7 kg/m(2)), and six obese Type 2 diabetic men (61.4+/-3.2 years, BMI 31.8+/-1.0 kg/m(2)). MEASUREMENTS: Subcutaneous adipose tissue PAI-1 mRNA and insulin sensitivity were quantified using RT-competitive PCR and euglycemic hyperinsulinemic clamp technique, respectively. RESULTS: Subcutaneous adipose tissue PAI-1 mRNA levels were higher in obese nondiabetic and Type 2 diabetic men than in lean nondiabetic men. PAI-1 mRNA levels decreased in the three groups during a 240-min euglycemic hyperinsulinemic clamp (P<0.05 for all groups), and a similar reduction was observed during a 240-min saline control study indicating that adipose tissue PAI-1 gene expression has diurnal variation and is not acutely controlled by hyperinsulinemia. The basal PAI-1 mRNA levels correlated positively with BMI, and waist-to-hip ratio; and negatively with whole-body glucose disposal rate in nondiabetic men. CONCLUSIONS: Subcutaneous adipose tissue PAI-1 mRNA expression is increased in obese nondiabetic or in Type 2 diabetic men. Subcutaneous adipose tissue PAI-1 mRNA expression is increased in proportion to visceral obesity and to the level of whole-body insulin resistance. Subcutaneous adipose tissue PAI-1 mRNA expression is not acutely regulated by insulin, and it is subject to a diurnal variation.

Adipose Tissue↗

Dyslipidemia and a reversible decrease in insulin sensitivity induced by therapy with 13-cis-retinoic acid.

BACKGROUND: 13-cis-Retinoic acid (Roaccutan) treatment is associated with disturbances in lipid and sometimes also in glucose metabolism. Thus, we investigated whether 13-cis-retinoic acid treatment decreases insulin sensitivity. METHODS: We studied 11 men [aged 24+/-2 years (mean+/-SEM), body mass index (BMI) 22.1+/-0.9 kg/m(2)] who received Roaccutan treatment for acne for a period averaging 5 months but who were otherwise healthy. The insulin sensitivity of the subjects was measured before, during and 1-3 months after the end of treatment using the euglycaemic hyperinsulinaemic clamp technique. RESULTS: Treatment with 13-cis-retinoic acid reduced total (59+/-4 vs 55+/-4 micromol/kg/min, p<0.02), oxidative (25+/-1 vs 22+/-2 micromol/kg/min, p<0.05) and non-oxidative (36+/-3 vs 33+/-3 micromol/kg/min, p=0.05) glucose disposal rate, and there was a 4% increase in HbA(1c) (from 5.2+/-0.07 to 5.4+/-0.07%, p<0.02). After treatment cessation these values returned to baseline. 13-cis-Retinoic acid treatment also resulted in increased very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol, increased VLDL triglyceride, and increased VLDL and LDL phospholipid concentrations. CONCLUSION: Treatment of acne with 13-cis-retinoic acid reduces insulin sensitivity and induces alterations in lipid metabolism resembling those of the insulin resistance syndrome.

Acne Vulgaris↗

Influence of heat on insulin absorption: different effects on amorphous and soluble insulins.

A rise in ambient temperature stimulates the absorption of soluble, rapid-acting insulin. In the present study, the effect of intensive heat (Finnish sauna) on the absorption of amorphous insulin from a subcutaneous injection site in eight patients with type I diabetes was examined. The rate of absorption was determined by external measurement of the disappearance rate of 125I-labelled intermediate-acting (Semilente) insulin. The sauna (twice for 25 min at 85 degrees C) failed to stimulate insulin absorption significantly or to lower blood glucose levels as compared to a control day at 22 degrees C. Thus, heat has a different effect on the pharmacokinetics of amorphous and soluble insulins.

Adolescent↗

Improved mealtime treatment of diabetes mellitus using an insulin analogue. Multicenter Insulin Lispro Study Group.

The absorption of regular human insulin from subcutaneous injection sites is delayed due to the self-association of insulin to multimeric forms. The insulin analogue insulin lispro has a weak self-association and a fast absorption rate. We examined the safety and efficacy of insulin lispro in the premeal treatment of patients with diabetes mellitus. A 12-month study was performed in 336 patients with insulin-dependent diabetes mellitus (IDDM) and 295 patients with non-insulin-dependent diabetes mellitus (NIDDM). The patients were randomized to inject either regular human insulin 30 to 45 minutes before eating, or insulin lispro immediately before each meal, in addition to basal insulin. The postprandial rise in serum glucose was lower in patients receiving insulin lispro than in those receiving regular human insulin therapy. At end point the increment was significantly lower at 1 hour (35%) and at 2 hours (64%) after the meal in IDDM patients; in NIDDM patients, the increment was nonsignificantly lower at 1 hour (19%) and significantly lower at 2 hours (48%). IDDM patients receiving insulin lispro achieved significantly lower glycated hemoglobin (HbA1c) levels in patients receiving regular human insulin (8.1% vs 8.3%). In NIDDM patients, HbA1c levels decreased equally in both treatment groups. Due to its fast absorption rate, insulin lispro improves postprandial control in diabetes. Insulin lispro can be considered one step toward optimal insulin therapy and improved patient convenience.

Adult↗

Fructose as a dietary sweetener in diabetes mellitus.

Human beings, including those with diabetes, have a desire for sweetness in the diet that cannot be ignored. The Food and Drug Administration ban of cyclamates and possible ban of saccharin have raised the question of alternative sweeteners for diabetic persons. Considerable interest has been focused on fructose, and both basic and clinical research has delineated its metabolic effects. This paper reviews the characteristics of fructose, as well as its physiology and metabolism in both normal and diabetic man. Findings seems to indicate that, in controlled diabetes, chronic or limited consumption of fructose at moderate doses has no adverse effects on the levels of blood glucose, cholesterol, or tryglycerides.

Adolescent↗

Combined effect of exercise and ambient temperature on insulin absorption and postprandial glycemia in type I patients.

We studied the combined effect of cool (10 degrees C) and warm (30 degrees C) ambient temperatures and physical exercise on insulin absorption and postprandial glycemia. Nine type I (insulin-dependent) diabetic patients were injected subcutaneously with their usual morning dose of short- and intermediate-acting human insulin and were given breakfast. Warm temperature was associated with 3- to 5-fold higher insulin absorption (P less than .01) and significantly lower blood glucose concentration (P less than .001) than cool temperature regardless of exercise. Exercise was associated with 28% (P less than .01) and 22% (P less than .05) increases in plasma insulin and maximally 5.7 mM (P less than .025) and 7.1 mM (P less than .01) lower blood glucose at cool and warm temperatures, respectively. Warm temperature and exercise had an additive effect in stimulating insulin absorption and in lowering blood glucose concentrations. However, there was no evidence of synergism between higher temperature and exercise in increasing free-insulin concentrations or decreasing blood glucose concentrations. To avoid postprandial hyperglycemia at cool temperature or hypoglycemia after exercise at warm temperature, appropriate adjustments in diet and insulin dose, or both, should be made.

Adult↗

Postprandial blood glucose response to exercise in type I diabetes: comparison between pump and injection therapy.

The effect of 40 min ergometer exercise on glucose homeostasis was studied 90 min after morning insulin and a breakfast meal in 11 insulin-dependent diabetic subjects treated with conventional injection therapy or with continuous subcutaneous insulin infusion with a portable pump. During conventional therapy plasma free insulin levels rose slowly (7 +/- 2 microU/ml) after the morning injection, allowing an excessive postprandial rise in blood glucose levels (6.4 +/- 0.4 mmol/L). Physical exercise was able to reverse this increase of blood glucose. With insulin infusion therapy, the initial rise in plasma free insulin after a preprandial bolus was 3.5-fold higher (25 +/- 4 microU/ml, P less than 0.01) and postprandial hyperglycemia was reduced by 70% as compared with conventional therapy (P less than 0.02). During exercise blood glucose fell 60% more in pump than in conventionally treated patients (P less than 0.02). However, the decline continued during the recovery period in conventionally treated but not in pump patients, resulting in a comparable total fall in blood glucose in both groups. Fluctuations in blood glucose were avoided when exercise was performed in the fasting state with basal insulin infusion. In conclusion, when exercise was performed after breakfast, the total fall in blood glucose was similar during pump and conventional therapy, although the fall was faster on the pump. This can be explained, at least in part, by greater peak insulin levels obtained by the pump. Since postprandial glucose levels are lower in pump than in conventionally treated patients, a risk for hypoglycemia induced by postmeal exercise may be greater in pump than in conventionally treated patients.

Adult↗

Normalization of insulin sensitivity in type I diabetic subjects by physical training during insulin pump therapy.

Seven type I (insulin-dependent) diabetic patients previously treated with continuous subcutaneous insulin infusion therapy participated in a 6-wk training program consisting of cycle ergometer exercise 1 h/day 4 times a week. Six nontraining pump-treated type I diabetic patients and 19 healthy subjects were studied as controls. The training improved maximal aerobic power (VO2 max) by 8% (P less than 0.05). Hemoglobin A1 was in the high normal range before training (8.6 +/- 0.4%) and remained unchanged. The ratio of HDL cholesterol to total cholesterol rose by 16% in the training group (P less than 0.01) but remained unchanged in the sedentary diabetic patients. Mean daily insulin requirements fell by 6% in the training group (P less than 0.01). This reduction occurred in the lunch and dinner boluses whereas the basal infusion rate remained unchanged. Insulin sensitivity as determined by the euglycemic clamp technique was 25-40% lower in the training group (5.24 +/- 0.48 mg/kg/min) and sedentary diabetic group (6.55 +/- 0.82 mg/kg/min) as compared with controls (8.69 +/- 0.77 mg/kg/min, P less than 0.025). After the training, the rate of glucose uptake rose by 60% (P less than 0.001) to 8.48 +/- 0.77 mg/kg/min, which was comparable to that in the controls, but remained unaltered in the sedentary diabetic group. Insulin binding to erythrocytes was comparable in the diabetic and healthy subjects, and remained unchanged. Basal hepatic glucose production was elevated in both groups of diabetic patients (P less than 0.05), whereas the suppression by insulin was normal, and both of these were unaltered by training.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗