Minimal influence of blood flow on interstitial glucose  and lactate-normal and insulin-resistant muscle

Holmäng, Agneta; Müller, Markus; Ok, Andersson; Lönnroth, Peter

doi:10.1152/ajpendo.1998.274.3.e446

Cited by 32 publications

(42 citation statements)

References 23 publications

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“…In muscle and fat, the basal A-I lactate concentration difference in type 2 diabetic subjects was similar to that in control subjects, which is in accordance with previous findings (40,42). In agreement with data previously reported by Jansson et al (41), which showed that subcutaneous adipose tissue is a significant source of whole-body lactate release in the postabsorptive state, the present data show that the interstitial lactate concentration in the subcutaneous tissue was significantly higher than in plasma in both subject groups.…”

Section: Ischemia and Muscle Glucose Uptake In Type 2 Diabetessupporting

confidence: 92%

Muscle glucose uptake is effectively activated by ischemia in type 2 diabetic subjects.

et al. 2000

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It has previously been shown that Wortmannin, a phosphatidylinositol 3-kinase inhibitor, inhibits glucose transport activated by insulin but not by ischemia, suggesting the importance of an activating mechanism that bypasses the insulin signal. To evaluate the relevance of this insulin-independent pathway in insulin-resistant subjects, the ability of ischemia to stimulate glucose uptake was investigated in 9 patients with type 2 diabetes and in 9 healthy control subjects (fasting glucose level 9.4 ± 0.8 vs. 5.1 ± 0.1 mmol/l, P < 0.001, in type 2 diabetic patients and control subjects, respectively; fasting insulin level insulin 8.1 ± 2.6 vs. 4.5 ± 0.7 mU/l, P < 0.05, respectively) matched for sex, age, and BMI. Arterial plasma and interstitial concentrations of glucose and lactate (measured by subcutaneous and muscle microdialysis) were recorded in the forearm before, during, and after ischemia induced locally for 20 min. During ischemia, the muscle interstitial glucose concentration decreased significantly from 7.7 ± 0.6 to 5.4 ± 0.4 mmol/l (P < 0.01) and from 4.4 ± 0.3 to 3.6 ± 0.3 mmol/l (P < 0.05) in type 2 diabetic patients and control subjects, respectively. The arterial-interstitial (A-I) glucose concentration difference was 1.7 ± 0.6 and 0.7 ± 0.3 mmol/l at basal, and it increased significantly to 3.5 ± 0.7 (P < 0.01) and 1.4 ± 0.3 mmol/l (P < 0.05) during ischemia in each group, respectively. Interstitial lactate increased significantly during ischemia from 0.8 ± 0.1 to 1.1 ± 0.1 mmol/l (P < 0.05) and from 0.5 ± 0.1 to 0.9 ± 0.2 mmol/l (P < 0.05), respectively. The A-I glucose concentration difference was abolished immediately postischemia and regained after ~15 min, whereas high interstitial lactate levels remained elevated throughout the study. Subcutaneous interstitial glucose concentrations remained unchanged during ischemia and postischemia in both groups, whereas the interstitial lactate concentration in adipose tissue increased during ischemia from 1.4 ± 0.2 to 2.0 ± 0.2 mmol/l (P < 0.05) and from 1.1 ± 0.1 to 1.8 ± 0.3 mmol/l (P < 0.05) in type 2 diabetic patients and control subjects, respectively. Plasma glucose and lactate levels were unchanged in both groups during the study period. The results show that in muscle, but not in adipose tissue, glucose uptake is efficiently activated by ischemia in insulin-resistant type 2 diabetic subjects, suggesting the activation of a putative alternative pathway to the insulin signal in muscle cells. Diabetes 49:1178-1185, 2000 I n skeletal muscle, insulin activates glucose transport through the translocation of GLUT4 from intracellular compartments to the plasma membrane (1). At least 2 distinct signaling pathways for the activation of glucose transport have been detected. In addition to the pathway used by the insulin signal, another pathway activated by contraction or ischemia has been described (2,3). One argument for multiple independent pathways for activation of glucose transport has been based on the observation that a maximal stimulation of glucos...

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Section: Ischemia and Muscle Glucose Uptake In Type 2 Diabetessupporting

confidence: 92%

Muscle glucose uptake is effectively activated by ischemia in type 2 diabetic subjects.

et al. 2000

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“…Significant differences for olanzapine were detected at baseline (6.22 ± 0.8 vs 9.40 ± 1.0 mU/ml, means ± SM, po0.02), as well as after 60 min (74 ± 4 vs 88 ± 6 mU/ml, means±SM, po0.016), 80 min (71±6 vs 92±5 mU/ml, means±SM, po0.001), and 100 min (78±4 vs 98±7 mU/ ml, means ± SM, po0.02) of steady-state clamp conditions. This parameter also represents a well-studied indicator for insulin resistance (Holmang et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Sacher

Mossaheb

Spindelegger

et al. 2007

Neuropsychopharmacol

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Atypical antipsychotics have been linked to a higher risk for glucose intolerance, and consequentially the development of type 2 diabetes mellitus (DM2). We have therefore set out to investigate the acute effects of oral administration of olanzapine and ziprasidone on whole body insulin sensitivity in healthy subjects. Using the standardized hyperinsulinemic euglycemic clamp technique we compared whole body insulin sensitivity of 29 healthy male volunteers after oral intake of either olanzapine 10 mg/day (n ¼ 14) or ziprasidone 80 mg/day (n ¼ 15) for 10 days. A significant decrease (po0.001) in whole body insulin sensitivity from 5.7 ml/h/kg ( ¼ mean, SM ¼ 0.4 ml/h/kg) at baseline to 4.7 ml/h/kg ( ¼ mean, SM ¼ 0.3 ml/h/kg) after oral intake of olanzapine (10 mg/day) for 10 days was observed. The ziprasidone (80 mg/day) group did not show any significant difference (5.2 ± 0.3 ml/h/kg baseline vs 5.1 ± 0.3 ml/h/kg) after 10 days of oral intake. Our main finding demonstrates that oral administration of olanzapine but not ziprasidone leads to a decrease in whole body insulin sensitivity in response to a hyperinsulinemic euglycemic challenge. Our finding is suggestive that not all atypical antipsychotics cause acute direct effects on glucose disposal and that accurate determination of side effect profile should be performed when choosing an atypical antipsychotic.

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“…It is known that the interstitial fluid concentration of glucose is considerably lower than plasma glucose [20], probably as a result of capillary diffusion capacity of glucose being a rate-limiting step for glucose metabolism. When insulin resistance is present, a combination of diminished myocellular glucose uptake and delivery may occur [20], and there have been reports that interstitial glucose concentrations may either increase [21], or decrease [20], depending on whether the defect in myocyte glucose transport is greater or less than the defect in glucose delivery. The question of glucose delivery as a rate-limiting step for muscle glucose uptake has been partly addressed by considering the relationship between bulk blood flow and glucose uptake.…”

Section: Discussionmentioning

confidence: 99%

Vascular and metabolic effects of methacholine in relation to insulin action in muscle

et al. 2006

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Aims/hypothesis: Methacholine (MC) is a nitric oxide vasodilator, but unlike other vasodilators, it potentiates insulin-mediated glucose uptake by muscle. The present study aimed to resolve whether this action was the result of a vascular effect of MC leading to increased muscle perfusion or a direct effect of MC on the myocytes. We hypothesise that vascular-mediated insulin-stimulated glucose uptake responses to MC occur at lower doses than direct myocyte MC-mediated increases in glucose uptake. Methods: The vascular and metabolic effects of this vasodilator were examined in rats in vivo using a novel local infusion technique, and in the pump-perfused rat hindlimb under conditions of constant flow. Results: Local infusion of low-dose MC (0.3 μmol/l) into the epigastric artery of one leg (test) in vivo markedly increased femoral blood flow and decreased vascular resistance, without effects in the contra-lateral leg. Capillary recruitment, but not glucose uptake, was increased in the test leg. All increases caused by MC were confined to the test leg and blocked by local infusion into the test leg of N ω -nitro-L-arginine methyl ester (L-NAME), but not by infusion of N ω -nitro-D-arginine methyl ester (D-NAME). In the constant-flow pumpperfused rat hindlimb, infusion of 0.6 μmol/l MC vasodilated the pre-constriction effected by 70 nmol/l noradrenaline or 300 nmol/l serotonin, and this was blocked by 10 μmol/l L-NAME. 2-Deoxyglucose in muscle was increased by 30 μmol/l MC (p<0.05), but was unaffected by 3 μmol/l MC. All increases in 2-deoxyglucose uptake by 30 μmol/l MC were blocked by 10 μmol/l L-NAME. Conclusions/interpretation: MC has dose-dependent effects both on the vasculature and on muscle metabolism. At low dose (0.3-3 μmol/l), MC is a potent vasodilator in muscle, both in vivo and in vitro, without metabolic effects; at higher doses (≥30 μmol/l) MC has a direct metabolic effect leading to increased glucose uptake. Both the vascular and metabolic effects are sensitive to L-NAME. The lowdose enhancement of insulin action in vivo by MC, which has been reported previously, thus seems to be attributable to vascular effects.

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Minimal influence of blood flow on interstitial glucose and lactate-normal and insulin-resistant muscle

Cited by 32 publications

References 23 publications

Muscle glucose uptake is effectively activated by ischemia in type 2 diabetic subjects.

Muscle glucose uptake is effectively activated by ischemia in type 2 diabetic subjects.

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Vascular and metabolic effects of methacholine in relation to insulin action in muscle

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