Mary MacDermott

THE INFLUENCE OF STREPTOZOTOCIN DIABETES AND METFORMIN ON ERYTHROCYTE VOLUME AND ON THE MEMBRANE POTENTIAL AND THE CONTRACTILE CHARACTERISTICS OF THE EXTENSOR DIGITORUM LONGUS AND SOLEUS MUSCLES IN RATS

The effects of streptozotocin (STZ) diabetes and the antihyperglycaemic agent metformin on the contractile characteristics of the limb skeletal muscles and on erythrocyte volume were examined in rats. After 8 weeks of diabetes, the tetanic tension of the extensor digitorum longus (EDL) muscle decreased and the half‐relaxation time of the soleus muscle increased. Endurance decreased in both muscles. Metformin treatment of the diabetic rats did not prevent the development of these contractile changes. Diabetes induced depolarisation in the EDL and soleus muscles. Following exposure to insulin, both muscles repolarised. Metformin treatment of control rats induced depolarisation in the EDL and soleus muscles, but in the depolarised EDL and soleus muscles of the diabetic rats metformin treatment caused no further depolarisation. The muscles of metformin‐treated control and diabetic rats hyperpolarised in the presence of insulin. Diabetes caused an increase in the volume of the blood erythrocytes. This was prevented by metformin treatment.

Contractile And Electrical Properties Of Sternohyoid Muscle In Streptozotocin Diabetic Rats

1. The effects of diabetes on the electrical and contractile function of skeletal muscle are variable, depending on muscle fibre type distribution. The muscles of the upper airway have a characteristic fibre distribution that differs from previously studied muscles, but the effects of diabetes on upper airway muscle function are unknown. Normally, contraction of upper airway muscles, such as the sternohyoids, dilates and/or stabilizes the upper airway, thereby preventing its collapse. Diabetes is associated with obstructive sleep apnoea in which there is collapse of the upper airway due to failure of the upper airway musculature to maintain airway patency. Therefore, the purpose of the present study was to determine the effects of diabetes on the electrical and contractile characteristics of upper airway muscle.

The influence of streptozotocin-induced diabetes and the antihyperglycaemic agent metformin on the contractile characteristics and the membrane potential of the rat diaphragm.

After 2 months of streptozotocin‐induced diabetes in rats, the membrane potential of the diaphragm muscle when measured in vitro at 30 degrees C was unchanged but the tetanic tension, the half‐relaxation time of the isometric twitch and the fatigue resistance were each reduced. Treatment of the diabetic rats with the antihyperglycaemic agent metformin prevented the decrease in half‐relaxation time and the greater degree of fatigue in the diaphragms. The possibility that changes in H+ and cyclic AMP concentrations in the diabetic muscles contributed to the decreased contractile function and that metformin acted by attenuating these changes is discussed.

The effects of dietary creatine supplements on the contractile properties of rat soleus and extensor digitorum longus muscles.

Daily creatine supplements (0.258 g kg−1) were administered to adult male Wistar rats (n= 7) in the drinking water. Age matched rats (n= 6) acted as controls. After 5‐6 days, contractile properties were examined in soleus and extensor digitorum longus (EDL) muscle strips in vitro at 30 °C. In soleus muscles, creatine supplements decreased the half‐relaxation time of the isometric twitch from 53.6 ± 4.3 ms in control muscles to 48.4 ± 5.5 ms but had no effect on twitch or tetanic tension or on twitch contraction time. In EDL muscles twitch tension, tetanic tension, twitch contraction and half‐relaxation times were all unaffected by creatine supplements. Creatine supplements increased the fatigue resistance of the soleus muscles but had no effect on that of the EDL muscles. After a 5 min low‐frequency fatigue test, tension (expressed as a percentage of initial tension) was 56 ± 3% in control soleus muscles, whereas that in the creatine‐supplemented muscles was 78 ± 6% (P < 0.01). In the EDL muscles, the corresponding values were 40 ± 2% and 41 ± 9%, respectively. The force potentiation which occurred in the EDL muscles during the initial 20‐30 s of the fatigue test was 170 ± 10% of initial tension in the control muscles 24 s after the initial stimulus train but was reduced (P < 0.01) to 130 ± 20% in the creatine‐supplemented muscles. In conclusion, soleus muscle endurance was increased by creatine supplements. EDL endurance was unaffected but force potentiation during repetitive stimulation was decreased.

Effects of creatine loading and depletion on rat skeletal muscle contraction

1. In humans, the effects of dietary creatine supplementation are controversial, with some studies showing increased muscle force and fatigue resistance and others reporting no effect on exercise performance. Little is known about the effects of creatine on muscle contractile properties.

Contractile properties of the diaphragm in creatine-fed rats.

1. Creatine feeding increases the oxidative capacity of type 1 skeletal muscle fibres and, in soleus muscles, consisting mainly of type 1 fibres, increases fatigue resistance. The diaphragm contains a relatively large content of type 1 fibres and respiratory muscle fatigue is a cause of respiratory failure. The aim of the present study was to determine whether creatine supplements increase fatigue resistance in the diaphragm.

Upper airway EMG responses to acute hypoxia and asphyxia are impaired in streptozotocin-induced diabetic rats

Obstructive sleep apnoea (OSA) is a major clinical disorder that is characterised by multiple episodes of upper airway obstruction due to failure of the upper airway dilator muscles to maintain upper airway patency. The incidence of OSA is high in many endocrine disorders including both insulin-dependent and non-insulin-dependent diabetes but the reasons for this are not known. We wished to test the hypothesis that central respiratory motor output to the upper airway muscles is preferentially impaired in a rat model of diabetes mellitus. Sternohyoid (SH) and diaphragm (DIA) EMG activities were recorded in control and streptozotocin (STZ)-induced diabetic rats during normoxia, hypoxia (7.5% O2 in N2) and asphyxia (7.5% O2 and 3% CO2) under pentobarbitone anaesthesia. SH EMG responses to acute hypoxia and asphyxia were significantly impaired in STZ-induced diabetic rats compared to control animals (+47.1 +/- 5.7 vs. +11.7 +/- 1.9% during hypoxia in control and diabetic animals respectively and +56.5 +/- 7.9 vs. +15.7 +/- 5.0% during asphyxia). However, DIA EMG responses to hypoxia and asphyxia were not different for the two groups. We propose that the higher prevalence of OSA in diabetic patients is related to preferential impairment of cranial motor output to the dilator muscles of the upper airway in response to physiological stimuli.