Glucose-induced Insulin Release from the Perfused Rat Pancreas Effects of D, L-Methionine Methyl Sulfonium Chloride, Urea and Ethyleneurea
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Sulfhydryl reagents such as organic mercurials, disulfide compounds and iodoacetate derivatives with a limited ability to penetrate the B cells have been well known to enhance glucose-induced insulin release even at concentrations lower than 1 mM.<BR>In order to investigate the participation of sulfhydryl groups in the plasma membrane in the release of insulin, we studied the effects of D, L-methionine methyl sulfonium chloride (MMSC) on glucose-induced insulin release and also of urea analogs on the B cells treated with MMSC using the perfused rat pancreas. The results are as follows.<BR>1. <B>Effect of MMSC on blood glucose of mice</B>: 0.1 ml and 0.2 ml of 200 mg/ml of MMSC solution, and 0.2 ml of saline solution as a control were injected intravenously from the tails of 24 hr-fasted mice. Blood glucose levels of mice treated with saline solution were 142±5mg/dl, (n=9, M±SEM) for a 24 hr-fed group, and 91±5 mg/d/(n=9) for a 24 hr-fasted group. Those of mice treated with MMSC solution were 183±9mg/d/(n=24) for a 24 hr-fed group and 121±6mg/dl (n=5) for a fasted group (MMSC; 0.2 ml), and 146±13 mg/dl (n=5) for a 24 hr-fed group (MMSC; 0.1 ml).<BR><B>2. Inhibitory and enhanced effects of MMSC on glucose-induced insulin release from the perfused rat pancreas</B>: Insulin release stimulated with 16.7mM glucose was biphasic, and the mean rate of insulin release during the first 6-min period and the maximal value were 90±12 ttU/ml/min, and 122±20μU/ml, respectively, The amount of insulin release in the second phase was kept at 130-150μU/ml. Dynamics of insulin release elicited with a combined infusion of 16.7 mM glucose and 10 mM MMSC following after a 15-min perfusion with 16.7 mM glucose showed a transient enahncement (maximal value; 226±6μU/ml) and then a gradual decrease (102±12μU/ml at 35 min). In the case of 0.5 mM MMSC, dynamics of insulin release did not chauge as compared to the control. MMSC at 10mM did not induce insulin release in the presence of 2.8 mM glucose (the mean rate of insulin release; 18±3 μU/ml/min). The amount of insulin release with 16.7mM glucose from the pancres preperfused with 2.8 mM glucose and 10mM MMSC for 10 min decreased to 47-50% of the control both in the first and second phases, and the mean rate of insulin release and the maximal value were 36±10 μU/ml/min and 53±16 μU/ml, respectively.<BR>3.<B> Recoverable and protective effects of urea analogs and nicotinamide on MMSC-treated pancreas</B>: Dynamics of insulin release stimulated with 16.7 mM glucose from the pancrefas treated with a combination of 2.8 mM glucose and 10 mM MMSC for 10 min, and then of 2.8mM glucose and 20 mM urea analogs for 15 min were significantly improved both in the early and second phases as compared to that without treatment of urea analogs. The mean rates of insulin release and the maximal values were 87±8μU/ml/min, 107±19μU/ml for urea treatment, anb 101±21μU/ml/min, 140±11μU/mi for ethyleneurea treantment, respectively. The mean rate of insulin release and the maximal value stimulated with 16.7 mM glucose, after 10 min-preperfusion with 10 mM MMSC and 20 mM nicotinaimde in the presence of 2.8 mM glucose, were 55±7 pU/ml/min and 97±2μU/ml, respectively. We concluded that MMSC may act on the B cell to inhibit and enhance insulin release through the mechanism of alkylation to the thiol groups, and urea analogs may improve insulin release from the MMSC-treated pancreas by unmasking the dithiol groups present at glucoreceptor sites.
- 一般社団法人 日本糖尿病学会の論文
一般社団法人 日本糖尿病学会 | 論文
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