5，7-Dihydroxy-3，4‘，8-trimethoxyflavone

7929833

Insulin-mediated vasodilation has been proposed as a determinant of in vivo insulin sensitivity. We tested whether sustained vasodilation with adenosine could overcome the muscle insulin resistance present in mildly overweight patients with essential hypertension. Using the forearm technique, we measured the response to a 40-min local intraarterial infusion of adenosine given under fasting conditions (n = 6) or superimposed on a euglycemic insulin clamp (n = 8). In the fasting state, adenosine-induced vasodilation (forearm blood flow from 2.6 +/- 0.6 to 6.0 +/- 1.2 ml min-1dl-1, P < 0.001) was associated with a 45% rise in muscle oxygen consumption (5.9 +/- 1.0 vs 8.6 +/- 1.7 mumol min-1dl-1, P < 0.05), and a doubling of forearm glucose uptake (0.47 +/- 0.15 to 1.01 +/- 0.28 mumol min-1dl-1, P < 0.05). The latter effect remained significant also when expressed as a ratio to concomitant oxygen balance (0.08 +/- 0.03 vs 0.13 +/- 0.04 mumol mumol-1, P < 0.05), whereas for all other metabolites (lactate, pyruvate, FFA, glycerol, citrate, and beta-hydroxybutyrate) this ratio remained unchanged. During euglycemic hyperinsulinemia, whole-body glucose disposal was stimulated (to 19 +/- 3 mumol min-1kg-1), but forearm blood flow did not increase significantly above baseline (2.9 +/- 0.2 vs 3.1 +/- 0.2 ml min-1dl-1, P = NS). Forearm oxygen balance increased (by 30%, P < 0.05) and forearm glucose uptake rose fourfold (from 0.5 to 2.3 mumol min-1dl-1, P < 0.05). Superimposing an adenosine infusion into one forearm resulted in a 100% increase in blood flow (from 2.9 +/- 0.2 to 6.1 +/- 0.9 ml min-1dl-1, P < 0.001); there was, however, no further stimulation of oxygen or glucose uptake compared with the control forearm. During the clamp, the ratio of glucose to oxygen uptake was similar in the control and in the infused forearms (0.27 +/- 0.11 and 0.23 +/- 0.09, respectively), and was not altered by adenosine (0.31 +/- 0.9 and 0.29 +/- 0.10). We conclude that in insulin-re15-76sistant patients with hypertension, adenosine-induced vasodilation recruits oxidative muscle tissues and exerts a modest, direct metabolic effect to promote muscle glucose uptake in the fasting state. Despite these effects, however, adenosine does not overcome muscle insulin resistance.

Insulin resistance and vasodilation in essential hypertension. Studies with adenosine.

A Natali, R Bonadonna, D Santoro, A Q Galvan, S Baldi, S Frascerra, C Palombo, S Ghione, and E Ferrannini

1994 Oct;

23463013

Phantom pain after arm amputation is widely believed to arise from maladaptive cortical reorganization, triggered by loss of sensory input. We instead propose that chronic phantom pain experience drives plasticity by maintaining local cortical representations and disrupting inter-regional connectivity. Here we show that, while loss of sensory input is generally characterized by structural and functional degeneration in the deprived sensorimotor cortex, the experience of persistent pain is associated with preserved structure and functional organization in the former hand area. Furthermore, consistent with the isolated nature of phantom experience, phantom pain is associated with reduced inter-regional functional connectivity in the primary sensorimotor cortex. We therefore propose that contrary to the maladaptive model, cortical plasticity associated with phantom pain is driven by powerful and long-lasting subjective sensory experience, such as triggered by nociceptive or top-down inputs. Our results prompt a revisiting of the link between phantom pain and brain organization.

Phantom pain is associated with preserved structure and function in the former hand area

Tamar R. Makin,a,1 Jan Scholz,1,2 Nicola Filippini,1,3 David Henderson Slater,4 Irene Tracey,1,5 and Heidi Johansen-Berg1

2013 Mar 5;