当前位置： SCI文献检索 > DIABETES期刊下所有文献 > Effects of tolbutamide pretreatment on the rate of conversion of newly synthesized proinsulin to insulin and the compartmental characteristics of insulin storage in isolated rat islets.

Effects of tolbutamide pretreatment on the rate of conversion of newly synthesized proinsulin to insulin and the compartmental characteristics of insulin storage in isolated rat islets.

Abstract：

:Tolbutamide (1 g/kg body wt) was administered to male rats for 3 days to determine the effects of this pretreatment on subsequent insulin biosynthesis and compartmental storage characteristics of freshly isolated islets. Islets were isolated 16 h after the last tolbutamide administration, at a time when fed plasma glucose concentrations were normal. Islet glucagon was unchanged but insulin content was significantly reduced (38 +/- 1.2 ng IRI/islet from seven untreated rats versus 7.9 +/- 1.2 ng IRI/islet from eight treated rats). After tolbutamide pretreatment, the rate of incorporation of 3H-leucine into islet proinsulin was unchanged, but the t1/2 of labeled proinsulin-to-insulin conversion was significantly (P less than 0.001) decreased from 36 to 20 min. After treatment, actual rates of glucose-stimulated insulin secretion were 50% lower, however, because due to the proportionately greater depletion of islet insulin content, the fractional rate of secretion was increased two-fold. After treatment, there was evidence of compartmental, heterogeneous insulin storage, and glucose still marked newly synthesized insulin for preferential release; however, the differential release of new and old insulin converged rapidly with time. Mathematical integration of the data suggested dilution of the newly synthesized insulin compartment with unlabeled insulin during the chase period, but additionally indicated more rapid mixing of newly synthesized with previously stored, unlabeled insulin. Thus, tolbutamide-treated rats partially compensated for acute insulin depletion by increasing the rate of proinsulin-to-insulin conversion, but not increasing the rate of proinsulin biosynthesis; doubling the glucose-stimulated fractional secretory rate of the depleted cellular insulin storage compartment; and retaining compartmental storage characteristics but mixing newly synthesized insulin more rapidly with the compartment of previously stored, unlabeled insulin.

journal_name

Diabetes

journal_title

Diabetes

authors

Gold G,Pou J,Gishizky ML,Landahl HD,Grodsky GM

doi

10.2337/diab.35.1.6

subject

Has Abstract

pub_date

1986-01-01 00:00:00

pages

6-12

issue

eissn

0012-1797

issn

1939-327X

journal_volume

pub_type

杂志文章

在线工具

Effects of tolbutamide pretreatment on the rate of conversion of newly synthesized proinsulin to insulin and the compartmental characteristics of insulin storage in isolated rat islets.