Methodological aspects, dose-response characteristics and causes of interindividual variation in insulin stimulation of limb blood flow in normal subjects

The response of limb blood flow to insulin is highly variable even in normal subjects. We examined whether physical fitness or differences in muscle morphology contribute to this variation. Maximal aerobic power, muscle fiber composition and capillarization, and the response of forearm glucose extraction and blood flow to a sequential hyperinsulinemic euglycemic clamp (serum insulin 374 +/- 10, 816 +/- 23, and 2,768 +/- 78 pmol/l) were determined in 16 normal males (age 25 +/- 1 yr, body mass index 24 +/- 1 kg/m2). Maximal aerobic power correlated positively with the proportion of type I fibers (r = 0.67, P < 0.01) and negatively with the proportion of type IIb fibers (r = -0.73, P < 0.01). Fiber composition but not blood flow correlated significantly with forearm and whole body glucose uptake. All doses of insulin significantly increased forearm blood flow, maximally by 123 +/- 21%. The ratio of capillaries per fiber was significantly correlated with basal and insulin-stimulated blood flow (0.58∑ 0.76, P < 0.05∑0.01). Mean arterial blood pressure and the insulin∑induced increase in blood flow were inversely correlated (r = ∑0.59, P < 0.05). We conclude that variation in glucose extraction is significantly determined by muscle fiber composition, whereas variation in insulin-stimulated blood flow is closely associated with muscle capillarization.

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Insulin action on adipocytes. Evidence that the anti-lipolytic and lipogenic effects of insulin are mediated by the same receptor

Biochemical Journal ◽

10.1042/bj1840355 ◽

1979 ◽

Vol 184 (2) ◽

pp. 355-360 ◽

Cited By ~ 25

Author(s):

S H L Thomas ◽

M H Wisher ◽

D Brandenburg ◽

P H Sönksen

Keyword(s):

Dose Response ◽

Insulin Action ◽

Insulin Analogues ◽

Bovine Insulin ◽

Maximal Effect ◽

Maximal Concentration ◽

Insulin Stimulation ◽

Chemically Modified ◽

Chemically Modified Insulins ◽

Stimulation Of

1. The dose-response relationships of insulin stimulation of lipogenesis and inhibition of lipolysis were studied simultaneously by using rat adipocytes to determine whether these different effects of insulin are mediated through the same or different sets of receptors. 2. The sensitivity (defined as the concentration of insulin required to produce a half-maximal effect) of the stimulated lipogenic response to insulin was not significantly different from the sensitivity of the anti-lipolytic response to insulin. The addition of different adrenaline and glucose concentrations did not alter the half-maximal concentration of insulin required to inhibit lipolysis. 3. The specificities of the lipogenic and antilipolytic responses were studied by using insulin analogues. The sensitivities of the lipogenic and anti-lipolytic responses were the same for five chemically modified insulins and hagfish insulin, which have potencies compared with bovine insulin of between 3 and 90%. 4. Starving rats for 48h significantly increased the sensitivities of both the antilipolytic and lipogenic responses to insulin, but the changes in the sensitivities of both lipogenesis and anti-lipolysis returned to that of fed rats. 5. We conclude that insulin stimulates lipogenesis and inhibits lipolysis over the same concentration range. These observations provide powerful evidence that the different effects of insulin are mediated through the same set of receptors.

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Neural regulation of canine skeletal muscle blood flow during hypoxic hypoxia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.257.5.h1581 ◽

1989 ◽

Vol 257 (5) ◽

pp. H1581-H1586

Author(s):

P. Kubes ◽

S. M. Cain ◽

C. K. Chapler

Keyword(s):

Skeletal Muscle ◽

Blood Flow ◽

Sciatic Nerve ◽

Muscle Blood Flow ◽

Hypoxic Hypoxia ◽

Potential Range ◽

Limb Blood Flow ◽

Neural Sympathetic Activity ◽

Peak Value ◽

Stimulation Of

Vascular resistance in canine limb skeletal muscle first increases and then decreases with prolonged arterial hypoxia, but whether neural sympathetic activity decreases with time is unknown. To assess the effectiveness of neurally mediated vasoconstrictor tone, we periodically cooled and rewarmed the sciatic nerve while nine anesthetized, paralyzed, pump-ventilated dogs were made hypoxic for 60 min by ventilation with 9.1% O2 in N2 (PaO2 = 24 +/- 2 mmHg). Before hypoxia, limb blood flow (QL) increased to a mean peak value of 111 ml.kg-1.min-1 with nerve cooling. With hypoxic hypoxia (HH), cardiac output increased but mean arterial pressure and limb blood flow remained the same. Nerve cooling at 15, 30, and 60 min of HH resulted in a pattern of progressively increasing mean peak QL values of 137, 151, and 160 ml.kg-1.min-1, respectively (P less than 0.05). Stimulation of the cut sciatic nerve at the end of the experiment established the maximum vasoconstriction that was possible and, thereby, the potential range that was available. The results showed that not only was neurally mediated vasoconstriction to skeletal muscle maintained throughout the hypoxic period, but that its intensity must have been increasing to overcome the local vasodilatory forces that were responsible for flow increasing even further with nerve cooling in prolonged hypoxia.

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