Fatty acids in the portal vein of the rat regulate hepatic insulin clearance.

The effects of FFA on hepatic insulin clearance were studied in the in situ perfused rat liver. Clearance decreased with increasing body weight (age) of the rats. When FFA were added to the perfusate a 40% reduction of hepatic removal of insulin was found over the normal, physiological range (less than 1,000 mumol/liter), less pronounced in heavier rats. When perfusion was started with high concentrations of FFA, inhibition was rapidly reversible, a phenomenon again blunted in heavier rats. In contrast to FFA, different glucose concentrations in the perfusate did not affect the hepatic insulin uptake in the presence of FFA within physiological concentrations. Thus, hepatic clearance of insulin is proportional to rat weight (age) and portal FFA concentrations. Other studies have recently shown that fatty acids inhibit insulin binding, degradation, and function in isolated rat hepatocytes, and that hepatic clearance is inversely dependent on hepatic triglyceride concentrations, both inhibitions reversible by prevention of fatty acid oxidation. It is suggested that the diminished hepatic clearance of insulin in heavier (older) rats is at least partly due to their relative obesity and increased hepatic triglyceride contents. This effect as well as that of portal FFA is probably mediated via fatty acid oxidation in the liver. This mechanism may have implications for the regulation of hepatic metabolism, and peripheral insulin concentrations.

Reduced hepatic insulin clearance in rats with dietary-induced obesity.

Insulin uptake in the in situ perfused liver from rats that were moderately obese after overfeeding was diminished in comparison with controls. The obese rats had higher levels of portal free fatty acids (FFA) and liver triglyceride contents but not of insulin concentration in the portal vein. There were strong negative correlations between hepatic triglyceride and insulin clearance (r approximately 0.8-0.9). The perfusions were performed with lower FFA concentrations than those in vivo in the portal vein. It is suggested that the inhibited insulin uptake in the obese rats was due to exposure of these livers in vivo to elevated FFA concentrations, and that this inhibition remained during the experiment and was associated with the triglyceride contents of the livers. It is also suggested that this mechanism was responsible for the moderate peripheral hyperinsulinemia seen in these rats. A mechanism of regulation of insulin uptake in the liver via FFA and liver triglyceride might be of importance in several conditions with hyperinsulinemia and known elevation of portal FFA, and liver triglyceride contents.

Muscle adaptations and glucose control after physical training in insulin-dependent diabetes mellitus.

Six men and three women with insulin-dependent diabetes (without complications) participated in physical training three times a week for 20 weeks. Physical training did not change the concentration of fasting blood-glucose, glucose excretion in urine or glucosylated haemoglobin (HbA1). However, the glucose disposal rate during euglycaemic clamp increased after training. In two patients a minor reduction of insulin dosage was necessary to alleviate slight hypoglycaemic episodes. The training resulted in significant increases in quadriceps isometric and dynamic strength and endurance. Maximal oxygen uptake increased by 8%, the activity of glycolytic enzymes in vastus lateralis muscle by 47% for hexokinase, and 30% for tri-osephosphate dehydrogenase and 25% for lactic dehydrogenase, the activity of oxidative enzymes by 42% for citrate synthase and 46% for 3-hydroxy-acyl-CoA-dehydrogenase. The glycogen concentration in the vastus lateralis muscle did not change significantly. Lipoprotein lipase activity did not change in muscle, nor in adipose tissue. The mean muscle fibre area increased by 25% and the area of FTa fibres by 30%. The new formation of capillaries around different muscle fibres was significant for FTb fibres (26%). The proliferation of capillaries, however, appeared to be insufficient to cope with the increased area of muscle fibres. As a result, the mean area of muscle fibre supplied by one capillary (a measure of diffusion distance) significantly increased after training for FTa fibres. It is concluded that with the exception of deficient proliferation of capillaries, patients with insulin-dependent diabetes mellitus show a normal central and peripheral adaptation to physical training. Physical training does not apparently improve blood glucose control in most cases, despite an increased insulin sensitivity.

Non-response of muscle capillary density and lipoprotein-lipase activity to regular training in diabetic patients.

Ten obese women with normal glucose tolerance, 10 obese patients with sulphonylurea-treated non-insulin-dependent diabetes (NIDD) and 11 patients with insulin-dependent diabetes (IDD; treated for 3-31 yr) took part in a 10-week programme of physical training in 50-min sessions, 2-3 times a week. As a result of training, maximal oxygen uptake increased significantly by about 18, 13 and 8% in the 3 groups, respectively, and citrate synthase in muscle increased significantly by 27-42%. The lipoprotein-lipase activity in muscle tissue (sampled by a needle-biopsy technique from the lateral vastus muscle) did not change. The number of capillaries/fibre in muscle tissue increased. This was accompanied by an increase in muscle fibre area, resulting in an unchanged number of capillaries/mm2. This may explain why the lipoprotein-lipase activity was unaltered. The latter activity in the group with IDD was lower than was predicted from the number of capillaries/mm2. This number was in fact larger than in the obese and NIDD groups. These results indicate that the increase in capillary density and lipoprotein-lipase activity that occurs in healthy young individuals as an effect of endurance training does not take place in obese, NIDD and IDD patients.

Home monitoring of blood glucose and insulin therapy without a photometer.

The BM-Test-Glycemie 1-44 test strip facilitates self-monitoring without the use of a photometer. In a population of 33 diabetic patients (age 24.8 +/- 2.9 years) 94% took part in home monitoring for 6-10 months. Of 29 who answered a questionnaire 25 preferred blood glucose testing to urine testing. In a "beta-cell school" it was taught that it is rational if home monitoring of blood glucose is combined with a tailored insulin treatment consisting of long-acting insulin (Ultralente) as a basal insulin and regular insulin (Actrapid) as a meal insulin. In a group of 24 labile diabetic patients 17 preferred this regime compared to earlier use of intermediate acting insulin and regular insulin. Six of these preferred the regular insulin to be taken in three doses. Hypoglycemia, when it occurred, was less distressing in symptoms than previously. Among patients with recent onset of diabetes active participation with dose reduction was seen during the honey-moon stage. The regime is logical and generative, offers a basis for an individualized therapy and a high remission frequency may be expected.

Type I diabetes and physical exercise.

Metabolic effects of physical exercise in type I diabetes are reviewed. Physical training leads to an increased insulin sensitivity but does not seem to influence the metabolic control. However, the metabolic control is of importance for the exercise results. Patients in a good control do not differ from normal individuals concerning working capacity, recovery after hypoglycemia and hormonal balance. Furthermore, abnormalities in the blood glucose homeostasis during exercise in type I diabetes are discussed as well as potential beneficial effects of physical training in the prevention of cardiovascular disease.

Home monitoring of blood glucose without a photometer.

The ability to estimate blood glucose values at home is an important way of improving diabetic control. In order to investigate whether it was possible to replace the photometers used at present colour discrimination of ReflotestR-Glucose and ReflotestR-Hypoglycemie strips are studied. It was found that a colour scale could be used with one discrete shade of colour for each millimol between 1 to 20 millimol/l. A new test strip Haemo-GlukotestR 20-800 for colour scale usage was tested. Correlation with hexokinase method as reference was found to be r = 0.97.