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Modulation of insulin secretion and glycemia by selective inhibition of cyclic AMP phosphodiesterase III.

Abstract：

:The effects of selective inhibition of cyclic AMP phosphodiesterase type III on insulin and glucose levels during an oral glucose challenge were evaluated in obese, diabetic ob/ob mice and in lean, non-diabetic littermates using the selective inhibitor, milrinone. Oral administration of milrinone increased plasma insulin levels both in ob/ob and in lean mice. Glucose tolerance was improved in lean, but not in ob/ob mice, where glucose levels were increased by milrinone treatment. In isolated hepatocytes from normal rats incubation with 200 microM milrinone caused a 30% increase in glucose release with a corresponding depletion of glycogen stores. Stimulation of isolated rat adipocytes with 200 microM milrinone increased glycerol release 7-fold. We conclude that selective inhibitors of cyclic AMP phosphodiesterase III are effective insulin secretagogues, but their therapeutic utility may be limited by their concurrent stimulation of lipolysis and hepatic glucose output.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Parker JC,VanVolkenburg MA,Nardone NA,Hargrove DM,Andrews KM

doi

10.1006/bbrc.1997.7034

subject

Has Abstract

pub_date

1997-07-30 00:00:00

pages

665-9

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(97)97034-0

journal_volume

236

pub_type

杂志文章

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