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Biomedical subjects

V Koivisto

Publications and source records attributed to V Koivisto.

At least 19 recordsLinked to original sources
PubMed2001

Glucose-induced insulin secretion is potentiated by a new imidazoline compound.

Sulfonylureas stimulate insulin secretion independent of the blood glucose concentration. This can lead to hypoglycaemia in type 2 diabetic patients. Over the last years a number of imidazoline derivatives have been identified that stimulate insulin secretion in a more glucose-dependent way. In agreement with this, our aim was to generate imidazoline derivatives with a potential for the treatment of type 2 diabetic patients. We developed the compound 2-[4-(4-chlorophenyl)-3-(2-methoxyethoxy)-2-naphthalenyl]-4,5-dihydro-1-H-imidazole monohydrochloride (LY389382) with an imidazoline moiety and investigated its effects on glucose-dependent insulin secretion in a beta-cell line, isolated rat islets and in vivo. We could demonstrate that LY389382 induces insulin secretion in MIN6 cells and rat islets in a glucose-dependent manner (EC50=1.1 microM and 0.3 microM, respectively). Furthermore during hyperglycaemia LY389382 increased insulin secretion in a dose-dependent manner in healthy rats, whereas the compound had no effect at euglycemia in a tenfold higher dosage. After 7 days of treatment of Zucker Diabetic Fatty [ZDF/ (Gmi/fa)] rats with LY389382 with a dose of 15 mg/kg twice daily the blood glucose concentration was reduced from 22.7 +/- 1.7 mM to 16.6 +/- 2.3 mM. During the same time period the glucose concentration increased from 21.7+/-1.7 mM to 28.9 +/- 1.3 mM in the vehicle-treated group (P<0.05). The drop of the insulin level was also inhibited by LY389382 in ZDF rats. In contrast to other well-characterised imidazolines that have been shown to induce a glucose-dependent insulin secretion only within a limited range of concentrations, LY389382 stimulates insulin secretion over a concentration range of at least two log units in a glucose-dependent manner. These data suggest that this imidazoline compound has a potential for the treatment of type 2 diabetes.

Animals↗
PubMed2000

Leptin during and after preeclamptic or normal pregnancy: its relation to serum insulin and insulin sensitivity.

Hyperleptinemia may be part of the insulin resistance syndrome. We studied serum leptin in preeclampsia, which is an insulin-resistant state, and sought associations between leptin and insulin or insulin sensitivity during and after pregnancy. Twenty-two proteinuric preeclamptic women and 16 normotensive controls were studied during the third trimester. Leptin was higher in preeclampsia (mean +/- SE, 34.6 +/- 3.9 v 20.0 +/- 3.3 microg/L, P = .002) and correlated directly with the level of proteinuria (r = .47, P = .03) and normal pregnancy (r = .52, P = .04), whereas insulin sensitivity as assessed by an intravenous glucose tolerance test showed no relationship to leptin. Leptin was 19.0 +/- 3.6 microg/L in 14 preeclamptic women and 10.1 +/- 2.0 microg/L (P = .11) in 11 controls 3 months after delivery. Leptin correlated directly with insulin both in preeclamptic puerperal women (r = .63, P = .02) and in controls (r = .81, P = .003). Leptin and insulin sensitivity correlated only in preeclamptic puerperal women (r = -.59, P = .02). In conclusion, (1) serum leptin is elevated in preeclampsia, (2) insulin is an important determinant of serum leptin in preeclamptic and normotensive women both during pregnancy and in the puerperium, and (3) hyperleptinemia may be part of the insulin resistance syndrome also in women with prior preeclampsia.

Adult↗
PubMed1998

Aerobic endurance exercise or circuit-type resistance training for individuals with impaired glucose tolerance?

The role of physical activity in the prevention of non-insulin-dependent diabetes mellitus (NIDDM) is of utmost importance. The aim of the present study was to evaluate the metabolic effects of aerobic endurance exercise and circuit-type resistance training in subjects with impaired glucose tolerance (IGT). Twenty-two individuals participated in the study. Fourteen subjects were enrolled in the aerobic endurance exercise part of the study; seven exercised regularly for six months, while seven served as controls. Maximal aerobic capacity (VO2max) was measured and insulin sensitivity and insulin secretion were assessed by a frequently sampled intravenous glucose tolerance test (FSIVGTT). Eight subjects participated in a circuit-type resistance training program for three months. Insulin sensitivity and substrate oxidation were then assessed using the euglycemic insulin clamp technique combined with indirect calorimetry. The aerobic endurance exercise program caused in increase in VO2max (21.6 +/- 1.9 to 25.4 +/- 2.4 ml/kg.min; p < 0.05) and HDL-cholesterol (1.14 +/- 0.06 to 1.23 +/- 0.08 mmol/l; p < 0.05), but no change in insulin sensitivity nor insulin secretion occurred. However, comparing the changes between the intervention and control group, the differences disappeared. Circuit-type resistance training increased insulin sensitivity (glucose disposal) by 23% (p < 0.05), primarily due to a 27% increase in non-oxidative glucose metabolism. Both circuit-type resistance training and aerobic endurance exercise seem to have beneficial effects in subjects with impaired glucose tolerance. However, by improving insulin sensitivity, circuit-type resistance training may postpone the manifestations of NIDDM in these high-risk individuals and should therefore be included in an exercise program for IGT subjects.

Blood Glucose↗
PubMed1997

Markers for the gene ob and serum leptin levels in human morbid obesity.

Leptin, the product of the ob gene, reduces body fat in genetically obese animals and circulates in elevated concentrations in the blood of obese patients. Polymorphic markers situated in the proximity of the human ob gene have recently been suggested to be linked to morbid obesity. We have studied the possible association between the microsatellite markers near the ob gene and morbid obesity in 252 morbidly obese patients with a mean body mass index (BMI) of 43 +/- 7 kg/m2, and 151 lean controls with a mean BMI of 22 +/- 2 kg/m2, and searched for linkage of these gene markers to obesity in 76 affected sib-pairs (BMI > or = 32). No significant association was observed between any of the eight microsatellite markers and morbid obesity, and affected-sib-pair analysis failed to show linkage of three selected ob gene markers to obesity in the sibships. There was a strong positive correlation between serum leptin levels and BMI in morbidly obese patients; a carrier status for either of the two most prevalent alleles of the microsatellite marker D7S530 in the vicinity of the ob gene was associated with serum leptin levels in the obese subjects. Two of the markers (D7S2519, D7S649) showed a significant relation to the weight-losing response to a 16-week very-low-calorie dietary intervention. We have thus been able to confirm a tight relationship between serum leptin and body mass but have found no evidence for genetic linkage of the ob gene markers to morbid obesity in a population considered to represent a genetic isolate and to be an ideal model for studies of complex disorders.

Adult↗
PubMed1997

[Diabetic nephropathy--screening, follow-up and treatment. Nephropathy Study Groups of The Finnish Diabetes Organization].

Owing to advances in the diagnosis and treatment of diabetic nephropathy, its management has become more active and is now initiated earlier after the presence of microalbuminuria has been established. In 1996 the Finnish Diabetic Association's nephropathy group issued recommendations concerning screening for diabetic nephropathy, and treatment and follow-up of patients with the disease.

Adolescent↗
PubMed1996

The effect of (steroid) immunosuppression on skeletal muscle glycogen metabolism in patients after kidney transplantation.

To examine the mechanisms by which immunosuppression by steroids impairs glycogen synthesis in human skeletal muscle, we measured glycogen synthase protein content and activity in muscle samples from 14 patients receiving corticosteroid therapy after kidney transplantation and in 20 healthy control subjects. A percutaneous muscle sample was taken before and at the end of a euglycemic hyperinsulinemic insulin clamp. Insulin-stimulated glucose disposal was reduced by 33% in kidney transplant patients compared with healthy controls (33.8 +/- 4.2 vs. 50.5 +/- 2.7 mumol (kg LBM)-1 min-1; P<0.01), primarily due to a decrease in nonoxidative glucose metabolism (14.2 +/- 3.3 vs. 32.3 +/- 2.7 mumol (kg LBM)-1 min-1; P<0.001). Glycogen synthase activity measured at both 0.1 mmol/L (17.6 +/- 2.6 vs. 24.0 +/- 2.2 nmol min-1 mg protein-1; P<0.05), and at 10 mmol/L glucose 6-phosphate (24.1 +/- 3.5 vs. 33.7 +- 2.4 nmol min-1 mg protein-1; P<0.05) and glycogen synthase protein concentrations (8.8 +/- 1.8 vs. 18.9 +/- 1.9 relative units per ng DNA; P<0.01) were lower in kidney transplant patients compared with controls. Glycogen synthase protein correlated with nonoxidative glucose metabolism (r=0.42; P=0.04). Alpha-actinin (used as a control of general protein degradation) was lower in kidney transplant patients compared with controls (4.4 +/- 0.8 vs. 9.6 +/- 1.1 cpm/ng DNA; P<0.01). In conclusion, corticosteroids cause insulin resistance, which correlates with impaired activation of glycogen synthase and decreased enzyme protein content. The decrease in glycogen synthase protein may reflect increased degradation rather than a defect in translation.

Adult↗
PubMed1994

Hospital use among diabetic patients and the general population.

OBJECTIVE: This register-based linkage study compared hospital use among diabetic and nondiabetic populations. The study focused on overall use, use by disease categories, and inpatient care caused by complications. RESEARCH DESIGN AND METHODS: The patient data were derived from the Hospital Discharge Register and the Central Drug Register in Finland. All drug-treated diabetic patients and discharges of patients in a 3-year period were included in the study. Hospital use was measured by inpatient days, mean length of stay, and discharge rate. RESULTS: Among diabetic patients were eligible for drug reimbursement, 14.2% had at least one hospital stay because of diabetes in a year, while 50.7% had at least one hospital stay for any cause. Only 12.4% of the nondiabetic population was hospitalized annually. Patients with diabetes as the principal diagnosis consumed about 3% of all inpatient days; patients who had diabetes either as the principal or as a subsidiary diagnosis used 8.3%; and people who were eligible for antidiabetic drug reimbursement used 13.3% of total inpatient days. Among diabetic children, the risk for hospitalization was 6.5 times higher than among nondiabetic children. With advancing age, causes other than diabetes increasingly dominated hospitalization among diabetic patients. Inpatient days because of cardiovascular diseases were 1.6-18 times more common among diabetic patients than among nondiabetic patients, depending on gender and age-group. Diabetic patients used many more hospital inpatient days than did the nondiabetic population for a number of other disease categories that are usually not related to diabetes. CONCLUSIONS: Hospital use among diabetic patients is substantially greater than that among the nondiabetic population, mainly because of cardiovascular and microvascular complications, but also because of diseases unrelated to diabetes.

Adolescent↗