Virus-induced alterations in cyclic adenosine monophosphate generation in hamster islets of Langerhans

E. J. Rayfield, K. J. Kelly

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Inoculation of golden Syrian hamsters with Venezuelan encephalitis (VE) virus results in a sustained diminution in glucose-stimulated insulin release that is correctable by cyclic (c) AMP analogs and phosphodiesterase inhibitors. This suggested the importance of directly measuring cAMP content in VE-infected and control islets in response to insulin secretagogues. The basal cAMP content of VE-infected islets (0.14 ± 0.02 pmol/μg islet DNA) was approximately half that of control islets (0.27 ± 0.02 pmol/μg islet DNA) (P < 0.05). In the presence of 10 μM glucagon (and 3 mM glucose), the rate of cAMP generation in VE-infected islets was only half that of control islets. With 10 mM α-ketoisocaproic acid, the rates of cAMP generation were indistinguishable between control and experimental groups. In response to 20 mM glucose and 3-isobutyl-1-methylxanthine (IBMX) (a phosphodiesterase inhibitor), cAMP generation in VE-infected islets was 81% (NS) of the control rate. When a more specific phosphodiesterase inhibitor, RO 20-1724, was used with 20 mM glucose, cAMP generation in the infected islets was only 44% (P < 0.001) of the control value. Insulin secretion over the perifusion period paralleled the cAMP levels. In the presence of 10 mM α-ketoisocaproic acid, there was no difference in insulin secretion between VE-infected and control islets, while there was a statistically significant (P < 0.05) difference with 10 mM glucagon or 20 mM glucose (in 1 mM RO 20-1724). These data point to a defect in the cAMP generation system of VE-infected islets, although additional factors involved in insulin secretion may also be impaired by the virus.

Original languageEnglish
Pages (from-to)958-963
Number of pages6
JournalJournal of Clinical Investigation
Volume77
Issue number3
DOIs
StatePublished - 1986

Fingerprint

Dive into the research topics of 'Virus-induced alterations in cyclic adenosine monophosphate generation in hamster islets of Langerhans'. Together they form a unique fingerprint.

Cite this