scholarly journals Spatially resolved changes in diabetic rat skeletal muscle metabolism in vivo studied by 31P-n.m.r. spectroscopy

1990 ◽  
Vol 268 (1) ◽  
pp. 111-115 ◽  
Author(s):  
R A J Challiss ◽  
M J Blackledge ◽  
G K Radda
Keyword(s):  
Skeletal Muscle ◽  
Muscle Metabolism ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Metabolic Dysfunction ◽  
Spatially Resolved ◽  
Phosphorus Containing ◽  
Stimulation Period ◽  
Isometric Twitch

Phase-modulated rotating-frame imaging (p.m.r.f.i.), a localization technique for 31P-n.m.r. spectroscopy, has been applied to obtain information on the heterogeneity of phosphorus-containing metabolites and pH in the skeletal muscle of control and streptozotocin-diabetic rats. Using this method, the metabolic changes in four spatially resolved longitudinal slices (where slice I is superficial and slice IV is deep muscle) through the ankle flexor muscles have been investigated at rest and during steady-state isometric twitch-contraction at 2 Hz. At rest, intracellular pH was lower, and phosphocreatine (PCr)/ATP was higher, throughout the muscle mass in diabetic compared with control animals. The change in PCr/ATP in diabetic muscle correlated with a decrease in the chemically determined ATP concentration. During the muscle stimulation period, the decrease in pH observed in diabetic muscle at rest was maintained, but not exacerbated, by the contractile stimulus. Stimulation of muscle contraction caused more marked changes in PCr/(PCr + Pi), PCr/ATP and Pi/ATP in the diabetic group. These changes were most evident in slice III, which contains the greatest proportion of fast glycolytic-oxidative (type IIa) fibres, in which statistically significant differences were observed for all metabolite ratios. The results presented suggest that some degree of heterogeneity occurs in diabetic skeletal muscle in vivo with respect to the extent of metabolic dysfunction caused by the diabetic insult and that regions of the muscle containing high proportions of type IIa fibres appear to be most severely affected.

Bioenergetic changes during contraction and recovery in diabetic rat skeletal muscle

1989 ◽  
Vol 256 (1) ◽  
pp. E129-E137 ◽  
Author(s):  
R. A. Challiss ◽  
M. Vranic ◽  
G. K. Radda
Keyword(s):  
Skeletal Muscle ◽  
Gastrocnemius Muscle ◽  
Diabetic Rats ◽  
Muscle Performance ◽  
Diabetic Rat ◽  
31P Nmr Spectroscopy ◽  
Control Groups ◽  
Isometric Twitch ◽  
Substrate Concentrations

Phosphorus nuclear magnetic resonance (31P-NMR) spectroscopy was used to assess the effects of hypoinsulinemia on skeletal muscle during contraction in vivo. Five groups of rats were studied: age-matched (CONA) and weight-matched (CONW) nondiabetic controls; rats given streptozotocin 21 days before study (UD); diabetic rats treated with insulin for 21 days (ITD); and insulin-treated diabetic rats with insulin treatment withheld for 72 h before study (IWD). Both UD and IWD had similar alterations in plasma substrate concentrations and an impairment in the rate of glycogen resynthesis after the stimulation protocol compared with ITD, CONA, and CONW. Pyruvate oxidation was decreased by 30-40% in mitochondria isolated from gastrocnemius of the UD group, whereas no significant decrease was observed for mitochondria from the IWD (or ITD) group(s). In UD, maintenance of gastrocnemius muscle isometric twitch tension at 1 Hz required exaggerated decreases in phosphocreatine (PCr) concentration and pH; at 5 Hz, muscle performance declined significantly, and intracellular pH decreased to lower values than observed for the control groups; during recovery, no impairment of PCr resynthesis was observed. We conclude that in skeletal muscle of UD 1) at 1 Hz there is an increased reliance on glycolytic mechanisms of ATP resynthesis and 2) at 5 Hz force failure may occur because of the decreased rate of pyruvate utilization.

Effect of insulin on intracellular pH and phosphate metabolism in human skeletal muscle in vivo

1991 ◽  
Vol 81 (1) ◽  
pp. 123-128 ◽  
Author(s):  
D. J. Taylor ◽  
S. W. Coppack ◽  
T. A. D. Cadoux-Hudson ◽  
G. J. Kemp ◽  
G. K. Radda ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Intracellular Ph ◽  
Inorganic Phosphate ◽  
Human Skeletal Muscle ◽  
Muscle Metabolism ◽  
Normal Subjects ◽  
Phosphate Concentration ◽  
Resonance Spectroscopy ◽  
Phosphorus Containing

1. 31P nuclear magnetic resonance spectroscopy and the hyperinsulinaemic-euglycaemic clamp were used simultaneously to assess the effect of insulin on intracellular pH and the major phosphorus-containing metabolites of normal human skeletal muscle in vivo in four normal subjects. 2. Insulin and glucose were infused for 120 min. Plasma insulin increased approximately 10-fold over pre-clamp levels (5.6 ± 0.9 m-units/l pre-clamp and 54 ± 5 m-units/l over the last hour of infusion; mean ± sem, n = 4). Plasma glucose concentration did not change significantly (5.4 ± 0.2 mmol/l pre-clamp and 5.5 ± 0.1 mmol/l over the last hour of infusion). 3. Insulin and glucose infusion resulted in a decline in the intracellular pH of forearm muscle of 0.027 ± 0.007 unit/h (P < 0.01), whereas in control studies of the same subjects, pH rose by 0.046 ± 0.005 unit/h (P < 0.001). 4. In the clamp studies, intracellular inorganic phosphate concentration rose by 18%/h, whereas ATP, phosphocreatine and phosphomonoester concentrations did not change. In plasma, inorganic phosphate concentration was 1.16 ± 0.05 mmol/l before infusion, and this decreased by a mean rate of 0.14 mmol h−1 l−1. No change was observed in any of these intracellular metabolites in the control studies. 5. The results show that, under physiological conditions, insulin does not raise intracellular pH in human muscle, and thus cannot influence muscle metabolism by this mechanism. The results also suggest that insulin causes a primary increase in the next flux of inorganic phosphate across the muscle cell membrane.

Regulation of hepatic triiodothyronine production in the streptozotocin-induced diabetic rat

1984 ◽  
Vol 247 (4) ◽  
pp. E526-E533
Author(s):  
A. S. Jennings
Keyword(s):  
Diabetic Rats ◽  
Diabetic Rat ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Insulin Administration ◽  
Progressive Decline ◽  
Serum T4 ◽  
Fasted Rats

The effect of diabetes on 3,5,3'-triiodothyronine (T3) production was determined in the isolated perfused rat liver. Induction of diabetes with streptozotocin resulted in decreased serum thyroxine (T4) and T3 levels and a progressive decline in hepatic T3 production over 5 days. The decline in T3 production resulted from decreased conversion of T4 to T3, whereas T4 uptake was unchanged. Insulin administration restored serum T4 and T3, hepatic conversion of T4 to T3, and T3 production to normal levels. When serum T4 levels in diabetic rats were maintained by T4 administration, the conversion of T4 to T3 and T3 production returned to control levels. However, restoration of serum T4 levels in fasted rats failed to correct the decrease in hepatic T4 uptake or T3 production. Glucagon, at supraphysiological concentrations in vitro and in vivo, slightly decreased T4 uptake and T3 production without altering the conversion of T4 to T3. These data suggest that the fall in serum T4 levels observed in diabetic rats is important in mediating the decreased hepatic conversion of T4 to T3 and T3 production.

scholarly journals 3-oxo acid coenzyme A-transferase in normal and diabetic rat muscle

1976 ◽  
Vol 158 (2) ◽  
pp. 509-512 ◽  
Author(s):  
A Fenselau ◽  
K Wallis
Keyword(s):  
Skeletal Muscle ◽  
Coenzyme A ◽  
Substrate Inhibition ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Functional Parameters ◽  
Rat Muscle ◽  
Coa Transferase ◽  
Normal Rat ◽  
Streptozotocin Diabetic Rats

The amounts of succinyl-CoA--3-oxo acid CoA-transferase (EC 2.8.3.5) decrease progressively in skeletal muscle in streptozotocin-diabetic rats, reaching after 10 days about 50% of the value in normal rat muscle. Electrofocusing studies indicate the occurrence of partial proteolysis of the enzyme in diabetic muscle. However, several functional parameters relating to acetoacetate utilization, including substrate inhibition, are quite similar for muscle transferase preparations from normal and diseased rats. The development of pathological ketoacidosis is discussed in the light of these observations.

scholarly journals Gosha-jinki-gan (a Herbal Complex) Corrects Abnormal Insulin Signaling

2004 ◽  
Vol 1 (3) ◽  
pp. 269-276 ◽  
Author(s):  
Bolin Qin ◽  
Masaru Nagasaki ◽  
Ming Ren ◽  
Gustavo Bajotto ◽  
Yoshiharu Oshida ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Protein Content ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Diabetic Rats ◽  
Metabolic Clearance ◽  
Long Term Effects ◽  
Β Protein

Previous studies have shown that the traditional herbal complex Gosha-jinki-gan (GJG) improves diabetic neuropathy and insulin resistance. The present study was undertaken to elucidate the molecular mechanisms related with the long-term effects of GJG administration on insulin actionin vivoand the early steps of insulin signaling in skeletal muscle in streptozotocin (STZ) diabetes. Rats were randomized into five subgroups: (1) saline treated control, (2) GJG treated control, (3) 2-unit insulin + saline treated diabetic, (4) saline + GJG treated diabetic and (5) 2-unit insulin + GJG treated diabetic groups. After seven days of treatment, euglycemic clamp experiment at an insulin infusion rate of 6 mU/kg/min was performed in overnight fasted rats. Despite the 2-unit insulin treatment, the metabolic clearance rates of glucose (MCR, ml/kg/min) in diabetic rats were significantly lower compared with the controls (11.4 ± 1.0 vs 44.1 ± 1.5;P< 0.001), and were significantly improved by insulin combined with GJG or GJG alone (26 ± 3.2 and 24.6 ± 2.2,P< 0.01, respectively). The increased insulin receptor (IR)-β protein content in skeletal muscle of diabetic rats was not affected by insulin combined with GJG administration. However, the decreased insulin receptor substrate-1 (IRS-1) protein content was significantly improved by treatment with GJG. Additionally, the increased tyrosine phosphorylation levels of IR-β and IRS-1 were significantly inhibited in insulin combined with GJG treated diabetes. The present results suggest that the improvement of the impaired insulin sensitivity in STZ-diabetic rats by administration of GJG may be due, at least in part, to correction in the abnormal early steps of insulin signaling in skeletal muscle.

In vivo leucine oxidation at rest and during two intensities of exercise

1982 ◽  
Vol 53 (4) ◽  
pp. 947-954 ◽  
Author(s):  
P. W. Lemon ◽  
F. J. Nagle ◽  
J. P. Mullin ◽  
N. J. Benevenga
Keyword(s):  
Skeletal Muscle ◽  
Specific Activity ◽  
Muscle Metabolism ◽  
Weighted Average ◽  
Mixed Diet ◽  
Sprague Dawley ◽  
Tracer Dose ◽  
Sprague Dawley Rats ◽  
14Co2 Production

After ingestion of a mixed diet containing a tracer dose (10 muCi) of L-[1–14C]leucine (Leu), 32 male Sprague-Dawley rats (70–90 g) remained at rest (R) or completed 1 h exercise at 80 (E80) or 40% VO2max (E40). 14CO2 production was assessed for 6 h (exercise occurred from h 2 to 3). Four rats were killed at 2, 3, 4, and 6 h (R), at 3 and 6 h (E80), and at 6 h (E40). Determinations were 1) tissue specific activity dpm X mumol-1 from a) mixed skeletal muscle (gastrocnemius, soleus, quadriceps, and hamstrings) and b) liver and 2) radioactivity remaining in the gastrointestinal tract (GIT). Leu oxidized (mumol) was estimated (14 CO2 dpm X tissue sp act dpm-1 X mumol-1) independently from skeletal muscle and liver. Results were 1) 14CO2 production increased in both E80 and E40 compared with R (P less than 0.05), 2) E80 14CO2 increase was greater than E40 (P less than 0.05), 3) GIT absorption was reduced in E80 and E40 compared with R (P less than 0.05), and 4) exercise Leu oxidation (weighted average of tissue estimates) was 26% greater than R (P less than 0.05). The origin and site of the increased Leu oxidation cannot be determined from the present data; however, due to the magnitude of increase in skeletal muscle metabolism relative to other tissues during exercise, it is probable that skeletal muscle plays a significant role.

Altered sensitivity of chronic diabetic rat heart to calcium

1983 ◽  
Vol 245 (6) ◽  
pp. E560-E567 ◽  
Author(s):  
D. R. Bielefeld ◽  
C. S. Pace ◽  
B. R. Boshell
Keyword(s):  
Rat Heart ◽  
Calcium Metabolism ◽  
Left Ventricular Pressure ◽  
Calcium Sensitivity ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Isolated Hearts ◽  
Pressure Development

An alteration in calcium metabolism in cardiac muscle was observed in diabetic rats 3 mo after streptozotocin treatment. Depression of cardiac output and left ventricular pressure development were more sensitive to decreased extra-cellular calcium in hearts from diabetic than from control animals and occurred within the normal physiological range of freely ionized serum calcium. This decrease in calcium sensitivity was not present after 2 wk of diabetes. In vivo treatment with insulin for 1 mo completely reversed the effect. Addition of octanoate (0.3 mM) to the perfusate of isolated hearts completely reversed the defect, whereas epinephrine (25 nM) only partially reversed it. When the glucose concentration of the perfusate was decreased, the function of diabetic hearts declined and was further diminished at decreasing calcium levels. Hearts from normal rats were unaffected. These results suggest that there is a defect in calcium metabolism or flux in the chronic diabetic rat heart.

Mirabegron, A Selective β3-Adrenoceptor Agonist Causes an Improvement in Erectile Dysfunction in Diabetic Rats

2019 ◽  
Author(s):  
Didem Yilmaz-Oral ◽  
Ecem Kaya-Sezginer ◽  
Dilan Askin ◽  
Yesim Hamurtekin ◽  
Serap Gur
Keyword(s):  
Erectile Dysfunction ◽  
Pde5 Inhibitor ◽  
Corpus Cavernosum ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Control Group ◽  
Sprague Dawley ◽  
Intracavernosal Injection ◽  
Relaxation Responses

Abstract Aim To investigate the possible beneficial effect of mirabegron [a selective β3-adrenoceptor (AR) agonist] treatment on erectile dysfunction (ED) in streptozotocin-induced diabetic rats. Methods Sprague-Dawley rats (n=20) were divided into two groups: control group and streptozotocin-induced diabetic group. In vivo erectile responses were evaluated after intracavernosal injection of mirabegron (0.4 mg/kg) in rats. The relaxation responses to electrical field stimulation (EFS, 10 Hz), sodium nitroprusside (SNP, 10 nM) and sildenafil (1 μM) of corpus cavernosum (CC) strips were examined after the incubation with mirabegron (10 μM). β3-ARs expression and localization were determined by Western blot and immunohistochemical analyses in CC tissue. Results In vivo erectile responses of diabetic rats [intracavernasal pressure (ICP) / mean arterial pressure, 0.17±0.01] were decreased, which were restored after administration of mirabegron (0.75±0.01, P<0.001). The basal ICP (7.1±0.6 mmHg) in diabetic rats was markedly increased after mirabegron (36.1 ±5.4 mmHg, P<0.01). Mirabegron caused markedly relaxation in diabetic rat CC after phenylephrine precontraction. The relaxation responses to EFS and sildenafil were reduced in diabetic CC, which were increased in the presence of mirabegron. Mirabegron enhanced SNP-induced relaxation response in both groups. The expression and immunoreactivity of β3-ARs localized to CC smooth muscle were observed in control and diabetic rats. Conclusions This is the first study to show that intracavernosal administration of mirabegron improved erectile function and neurogenic relaxation of CC in diabetic rats. These results may be supported by further studies using combinations of mirabegron and phosphodiesterase type 5 (PDE5) inhibitors for the treatment of diabetic ED, especially in patients who do not respond to PDE5 inhibitor therapy.

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