Continuous glucose monitoring system during physical exercise in adolescents with type 1 diabetes.

AIM: Continuous glucose monitoring system (CGMS) provides detailed information on glucose fluctuations. The aim was to establish whether CGMS could be used during physical exercise and whether it detects more episodes of hypoglycaemia and hyperglycaemia than frequent blood glucose measurements. METHODS: Adolescents with type 1 diabetes (12 girls and 47 boys) participated in three annual sports camps that lasted for 3-4 days and included different types of exercise: soccer, floorball + cross-country skiing and golf. During the study, blood glucose values, mean 8.7 ± 3.3 per day, were obtained with Hemocue in parallel with the CGMS. RESULTS: Ninety-eight per cent of the participants used the sensor at all times during the camps. Eighty-seven per cent of the sensors gave adequate signals for 24 h and 66% for 48 h. Median durations of hypoglycaemia and hyperglycaemia were 1.7 h per day and 3.8 h per day, respectively. The CGMS identified significantly more episodes of hypoglycaemia (p < 0.005) and hyperglycaemia (p < 0.005) during the day and night than frequent blood glucose tests. CONCLUSION: We demonstrate that, even during days that included episodic strenuous physical exercise, CGMS could provide useful information on glucose fluctuations during day and night, albeit with significant failure rates.

Changes in beta(2)-adrenoceptor expression and in adenylyl cyclase and phosphodiesterase activity in human uterine leiomyomas.

Uterine leiomyoma is a very common benign tumour with unclear pathophysiology in adult women. In the present study we have investigated the expression level of alpha(2)- and beta(2)-adrenoceptors, and the adenylyl cyclase and phosphodiesterase activity in leiomyoma tissue compared with adjacent myometrium. Our results show that the alpha(2)/beta(2)-adrenoceptor ratio is increased in leiomyoma, due to a significant decrease in beta(2)-adrenoceptor expression. These changes were not due to an increased innervation, as the tumour tissue was completely devoid of nerve fibres. Moreover, the adenylyl cyclase activity of leiomyoma membranes was found to be approximately 50% lower, whereas the phosphodiesterase activity was significantly increased (by approximately 100%). We found that stimulating an increase in intracellular cyclic AMP, by adenylyl cyclase activity through beta(2)-adrenoceptors (isoprenaline), by direct enzyme activation (forskolin), or by inhibition of phosphodiesterase activity (papaverine), potently blocked both protein and DNA synthesis in cultured leiomyoma smooth muscle cells. Our results imply the adrenoceptors might be involved in, or a consequence of, leiomyoma growth. The results also suggest a new interesting approach for leiomyoma pharmacotherapy.

Multiple alpha 2-adrenoceptor signalling pathways mediate pigment aggregation within melanophores.

It has previously been shown that alpha 2-adrenoceptors (alpha 2-ARs) mediate pigment granule (melanosome) aggregation in melanophores of the teleost fish Labrus ossifagus. The present investigation scrutinized the signalling mechanisms of melanosome aggregation induced by sympathetic nerve stimulation or by exogenous addition of alpha-AR agonists and cAMP analogues. The following was observed: i) nerve-induced melanosome aggregation was associated with a rapid decrease in the cAMP level; ii) noradrenaline or medetomidine (an alpha 2-AR agonist) caused melanosome aggregation and reduced the cAMP content; iii) RP-8-Cl-cAMP, a membrane-permeating inhibitor of protein kinase A induced melanosome aggregation; and iv) B-HT 920 (an alpha 2-AR agonist) and methoxamine (an alpha 1-AR agonist) induced melanosome aggregation, although they did not reduce cAMP. It has been suggested that in some teleost species alpha 1-ARs mediate melanosome aggregation by increasing the level of intracellular calcium. However, we found that the effect of methoxamine in melanophores from Labrus ossifagus could be blocked by yohimbine (an alpha 2-AR antagonist) but not by equimolar concentration of prazosin (an alpha 1-AR antagonist). Furthermore, 1 microM ionomycin (a calcium ionophore) did not induce melanosome aggregation. Our findings therefore do not indicate that alpha 1-ARs and/or an increase in intracellular calcium mediate melanosome aggregation in Labrus ossifagus. Our results suggest that alpha 2-AR-mediated melanosome aggregation is induced by multiple signalling pathways. One of these involves a reduction in cAMP, but none involves an increase in intracellular calcium.

Characterization of alpha2-adrenoceptor subtypes in pregnant human myometrium.

The aim of the present investigation was to determine which subtypes of the alpha2-adrenoceptors are being expressed in the human pregnant myometrium at term pregnancy. In radioligand binding studies, the specific binding of [3H]rauwolscine to human myometrial membranes was specific and of high affinity with Kd of 2.8 +/- 0.6 nMand Bmax of 95 +/- 5 fmol/mg protein. Results from competition for the binding of [3H]rauwolscine using subtype-selective ligands, oxymetazoline (alpha2A-subptype), chlorpromazine (alpha2B-subtype) and prazosin (alpha2B-alpha2C-subtype), suggested that the alpha2A- and alpha2B-subtypes are being co-expressed. In order to examine if also the alpha2C-subtype is being expressed we used an optimal concentration of oxymetazoline or chlorpromazine which would block the high-affinity site, equivalent to the alpha2A- and alpha2B-subtype respectively. Competition curves of both oxymetazoline and chlorpromazine still showed a significantly better fit using a two-site model, suggesting that the alpha2C-subtype also is being expressed. The expression of alpha2C-subtype mRNA was confirmed using reverse transcription-polymerase chain reaction on mRNA isolated from myometrial biopsies. In conclusion, our results suggest that all three subtypes of alpha2-adrenoceptors are being coexpressed in the human myometrium at term pregnancy and that alpha2-expression is dominated by the alpha2A-subtype.