Impact of Diabetes on Microvascular PO2 and Tension in Rat Extensor Digitorum Longus (EDL) Muscle

Abstract

Microvascular PO (PO m) on-kinetics are accelerated in the spinotrapezius muscle of diabetic rats (Am J Physiol 283: H926, 2002). The faster PO2m on-kinetics in diabetic skeletal muscle appear to be associated with the structural and functional changes in the microcirculation, however direct correlations to muscle tension development have not been performed. PURPOSE: To test the hypotheses that; (1) the faster PO2m on-kinetics in diabetic rat skeletal muscle are associated with greater oxygen utilization due to greater tension development, and (2) that insulin therapy will ameliorate the changes in PO2m on-kinetics and tension development. METHODS: Female Sprague-Dawley rats were divided into control (C, n=9; blood glucose, 105 ± 13 mg/dL) and diabetic groups (n=17, 50 mg/kg STZ). Diabetics were subdivided into untreated (D, n=9; glucose, 435 ± 37 mg/dL), and insulin treated diabetic (I, n=8; 4 units insulin glargine/day; glucose, 355 ± 31 mg/dL) groups. Experiments were performed 8–10 wks later. PO2m (phosphorescence quenching) was measured at rest and during electrically stimulated muscle contractions (1 Hz, 6.5 V, 2 ms duration). The distal tendon of the EDL was attached to a force transducer and muscle tension analyzer. Significance at P<0.05. RESULTS: D rats had lower body weight (C, 302 ± 8; D, 225 ± 17; I, 289 ± 5 g) and EDL weight (C, 168 ± 8; D, 90 ± 11; I, 150 ± 4 mg) compared to C and I. Mean arterial pressure (C, 131 ± 10; D, 128 ±7; I, 125 ± 6 mmHg) and arterial PO2 (C, 85 ± 2; D, 76 ± 4; I, 72 ± 2 mmHg) were similar. Resting PO2m was not different among groups (C, 32 ± 3; D, 30 ± 2; I, 25 ± 2 mmHg), however the fall in PO2m during steady-state contractions was less in D and I (C, −20 ± 2; D, −11 ± 2; I, −13 ± 1 mmHg) compared to C. At the onset of contractions, the time delay was similar (C, 5 ± 1; D, 6 ± 1; I, 5 ± 1 s), but the time constant was less in D and I rats (C, 21 ± 3; D, 14 ± 2; I, 12 ± 1 s). Absolute peak twitch tension (g) was less in D rats, however, due to marked atrophy in D, peak tension per muscle mass was not different (C, 165 ± 19; D, 226 ± 18; I, 180 ±17g/g) CONCLUSION: Insulin treatment prevented the diabetes-induced decreases in body weight and muscle atrophy, but did not restore the PO2m on-kinetics, or magnitude of fall in PO2m. Average peak tension development per g EDL was not different among C, D and I, suggesting that oxygen consumption was similar. These data imply there is a slower increase in oxygen delivery relative to consumption at the onset of contractions in D and I, but that steady-state oxygen delivery is greater, as reflected in a reduced fall in PO m. (Supported by KCOM Graduate Program Committee and the American Heart Association, Heartland Affiliate.)