Disease duration as an indicator of the efficacy of liraglutide in patients with type 2 diabetes mellitus.

Comment on the article of Usui et al. Retrospective cohort study of obese patients with type 2 diabetes mellitus (n = 69) demonstrates that the glucose-lowering effect of liraglutide as add on therapy to insulin relies on the remaining beta-cell function in type 2 diabetes. Shorter disease duration implies a more favourable prognosis for response on instantaneous substitution of insulin with liraglutide (HR 2.39 (95% CI: 1.20-4.76).

The effect of acute exercise on glycogen synthesis rate in obese subjects studied by 13C MRS.

In obesity, insulin-stimulated glucose uptake in skeletal muscle is decreased. We investigated whether the stimulatory effect of acute exercise on glucose uptake and subsequent glycogen synthesis was normal. The study was performed on 18 healthy volunteers, 9 obese (BMI = 32.6 ± 1.2 kg/m(2), mean ± SEM) and 9 lean (BMI = 22.0 ± 0.9 kg/m(2)), matched for age and gender. All participants underwent a euglycemic hyperinsulinemic clamp, showing reduced glucose uptake in the obese group (P = 0.01), during which they performed a short intense local exercise (single-legged toe lifting). Dynamic glucose incorporation into glycogen in the gastrocnemius muscle before and after exercise was assessed by (13)C magnetic resonance spectroscopy combined with infusion of [1-(13)C]glucose. Blood flow was measured to investigate its potential contribution to glucose uptake. Before exercise, glycogen synthesis rate tended to be lower in obese subjects compared with lean (78 ± 14 vs. 132 ± 24 µmol/kg muscle/min; P = 0.07). Exercise induced highly significant rises in glycogen synthesis rates in both groups, but the increase in obese subjects was reduced compared with lean (112 ± 15 vs. 186 ± 27 µmol/kg muscle/min; P = 0.03), although the relative increase was similar (184 ± 35 vs. 202 ± 51%; P = 0.78). After exercise, blood flow increased equally in both groups, without a temporal relationship with the rate of glycogen synthesis. In conclusion, this study shows a stimulatory effect of a short bout of acute exercise on insulin-induced glycogen synthesis rate that is reduced in absolute values but similar in percentages in obese subjects. These results suggest a shared pathway between insulin- and exercise-induced glucose uptake and subsequent glycogen synthesis.

Real-time contrast imaging: a new method to monitor capillary recruitment in human forearm skeletal muscle.

OBJECTIVE: Muscle capillary perfusion can be measured by contrast-enhanced ultrasound. We examined whether a less time-consuming ultrasound technique, called "real-time imaging," could be used to measure capillary recruitment in human forearm skeletal muscle. METHODS: We measured microvascular blood volume and microvascular flow velocity using bolus injections of contrast microbubbles after forearm muscle exercise and a two-hour infusion of insulin into the brachial artery (both associated with capillary recruitment) and after sodium nitroprusside infusion (no changes in flow distribution). RESULTS: After an intravenous bolus injection of the contrast agent, the steady-state concentration of contrast agent in forearm muscle lasted long enough (approximately 190 seconds) for the duration of the measurements (which take 70-80 seconds), rendering the continuous infusion of microbubbles unnecessary. Microvascular blood-volume measurements showed a good short-time reproducibility and a good reproducibility after repositioning of the forearm. Reproducibility of microvascular flow velocity was too low. Exercise and insulin infusion both increased microvascular blood volume, consistent with capillary recruitment. Sodium nitroprusside had no effect. CONCLUSION: Real-time contrast imaging, after bolus injections of an ultrasound contrast agent, provides reliable information about capillary recruitment in human forearm skeletal muscle, and may offer a valuable tool in studying human (patho)physiology.

Adrenergic receptor stimulation attenuates insulin-stimulated glucose uptake in 3T3-L1 adipocytes by inhibiting GLUT4 translocation.

Activation of the sympathetic nervous system inhibits insulin-stimulated glucose uptake. However, the underlying mechanisms are incompletely understood. Therefore, we studied the effects of catecholamines on insulin-stimulated glucose uptake and insulin-stimulated translocation of GLUT4 to the plasma membrane in 3T3-L1 adipocytes. We found that epinephrine (1 microM) nearly halved insulin-stimulated 2-deoxyglucose uptake. The beta-adrenoceptor antagonist propranolol (0.3 microM) completely antagonized the inhibitory effect of epinephrine on insulin-stimulated glucose uptake, whereas the alpha-adrenoceptor antagonist phentolamine (10 microM) had no effect. When norepinephrine was used instead of epinephrine, the results were identical. None of the individual selective beta-adrenoceptor antagonists (1 microM, beta(1): metoprolol, beta(2): ICI-118551, beta(3): SR-59230A) could counteract the inhibitory effect of epinephrine. Combination of ICI-118551 and SR-59230A, as well as combination of all three selective beta-adrenoceptor antagonists, abolished the effect of epinephrine on insulin-stimulated glucose uptake. After differential centrifugation, we measured the amount of GLUT1 and GLUT4 in the plasma membrane and in intracellular vesicles by means of Western blotting. Both epinephrine and norepinephrine reduced insulin-stimulated GLUT4 translocation to the plasma membrane. These results show that beta-adrenergic (but not alpha-adrenergic) stimulation inhibits insulin-induced glucose uptake in 3T3-L1 adipocytes, most likely via the beta(2)- and beta(3)-adrenoceptor by interfering with GLUT4 translocation from intracellular vesicles to the plasma membrane.