Effects of Adrenodemedullation on In Vivo Insulin-Stimulated Glucose Utilization in Relation to Glycolysis in Rat Peripheral Tissue.

Abstract

Abstract. The effect of adrenodemedullation (ADMX) on insulin action was examined in anesthetized rats by means of a three-step euglycemic clamp procedure (insulin infusion rate: 0, 6.0 and 30.0 mU•kgBW-1•min-1) combined with a microdialysis technique in skeletal muscle and adipose tissue. The dialysate lactate levels in the above tissues increased in parallel with the plasma lactate levels during the sequential euglycemic clamp. In the euglycemic clamp, the glucose infusion rate (GIR) was significantly (P<0.01) higher in ADMX rats (13.41±0.82 mg•kgBW-1•min-1) than in SHAM rats (10.21±0.87 mg•kgBW-1•min-1) during the 6.0-mU•kgBW-1•min-1 insulin infusion, and the lack of a significant difference between ADMX and SHAM rats was observed during the 30-mU•kgBW-1 •min-1 insulin infusion. In skeletal muscle, the concentration of lactate in dialysate was significantly higher in ADMX rats (9.29±1.01 mg/dl) than in SHAM rats (6.22±0.47 mg/dl) (P<0.05) at an insulin infusion rate of 6.OmU•kgBW-1•min-1. In adipose tissue, no significant difference in dialysate lactate levels was found between ADMX and SHAM rats at any insulin infusion rate. These results suggest that 1) it is possible to determine insulin action in skeletal muscle and adipose tissue in vivo by using the microdialysis technique, that 2) ADMX appears to result in a significant increase in insulin sensitivity, and that 3) lactate formation increased in skeletal muscle, but not in adipose tissue. Correspondence to: Dr. Yoshiharu OSHIDA, Research Center of Health, Physical Fitness and Sports, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-01, Japan maximal insulin response for glucose transport in rat [7], and that chronic fJ-adrenoreceptor stimulation with norepinephrine increases insulin-stimulating glucose disposal in vivo by increasing the insulin sensitivity of rat peripheral tissues [8].It has been known that plasma levels of norepinephrine are increased and those of epinephrine are decreased one week after ADMX in rats [9]. Under these conditions it could be hypothesized that insulin-stimulated glucose uptake is increased in peripheral tissue in vivo considering the above previous reports [7, 8, 9]. In order to confirm this hypothesis, we have used a sequential euglycemic hyperinsulinemic clamp technique, adapted in our laboratory for use in rats, in combination with a microdialysis technique

Rat C peptide I and II stimulate glucose utilization in STZ-induced diabetic rats

“…Metabolic clearance rate for glucose (MCR, ml´kg ±1´m in ±1 ) was then obtained from GDR divided by the corresponding blood glucose concentration. The GDR and the MCR from 60 to 90 min for the euglycaemic clamp procedure were regarded as indices of insulin action in peripheral tissues, since a plateau glucose infusion rate was achieved during this time, as reported previously [14,15]. In a final group of rats N-monomethyl-l-arginine (l-NMMA, Calbiochem-Novabiochem, Nottingham, England) was infused (1 mg × kg ±1 × min ±1 ) in diabetic rats together with C peptide I (0.05 nmol × kg ±1 × min ±1 ) during low-dose insulin infusion according to the same protocol as described above.…”

Effect of Daily Voluntary Running onIn VivoInsulin Action in Rat Skeletal Muscle and Adipose Tissue as Determined by the Microdialysis Technique

“…During the microdialysis, the probe was connected to a microinfusion pump (Carnegie Medicin, Sweden) and continuously perfused at 1 pl/min with Krebs-Henseleit bicarbonate (KHB) buffer (except that the Ca2+ concentration was reduced from 5 to 2.5mEqll). Our recent study (24) has shown that the in vim recovery of lactate (dialysate concentrations vs medium concentration x 100) is 60.8 + 1.2% at a perfusate flow rate of 1 yllmin and that the recovery remains constant at the lactate concentration of up to at least 30.00 mgldl. The dialysate was collected at the outlet of the probe every 15 min for analysis of lactate following a stabilization period of 60 min.…”

“…We hypothesize that one of the responsible mechanisms for these conflicting data could be due to increased glycolysis in peripheral tissues since increased lactate production was found during hyperinsulinemic euglycemic clamp (3) and peripheral tissues were major contributors to increased insulin action by physical training (7). Recently, we have developed a sequential eugiycemic clamp in combination with a microdialysis technique in skeletal muscle and adipose tissue in the rat (24). Using this technique, we have shown that the dialysate insulin-stimulated lactate level in the above mentioned tissues is mainly a reflection of lactate formation and changes in parallel with glucose infusion rate (GIR) during the euglycemic clamp.…”

“…m = S C ; M = V R M = S C , U = V R60-70 mg/dl and 12-20 pU/ml, respectively. Moreover, our recent study(24) has indicated that the dialysate concentration of lactate in muscle and adipose tissue depends upon the blood concentration at the basal insulin levels, and is mainly derived from tissue formation of lactate during the euglycemic clamp since the dialysate lactate concentrations were much higher than the values obtained by multiplication of the blood lactate levels by in vitro dialysis recovery of iactate (60.8 f I .2 %).…”

Intramuscular 3-Hydroxybutyrate Levels after 60 Tetani/Min Contraction in Diabetic and Non-Diabetic Rats.

“…The in vitro recovery rates of 3-OHBA and lactate (dialysate concentration vs. medium concentration x 100) were measured as previously reported [10,14] and were then 60.8 ± 3.4% and 56.6 ± 1.1%, respectively, at a perfusate flow rate of 1.4 ,ul/min. Probes were placed in media containing varying concentrations of 3-OHBA (20 to 800 4umol/l) and lactate (0.3 to 3.0 mmol/l) and were continuously perfused with KHB at 1.4 4u1/min.…”