HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Thams, P. Articles by Capito, K. Search for Related Content PubMed PubMed Citation Articles by Thams, P. Articles by Capito, K.

Glucose triggers protein kinase A-dependent insulin secretion in mouse pancreatic islets through activation of the K⁺_ATP channel-dependent pathway

Department of Medical Biochemistry and Genetics, Building 6.5, The Panum Institute, University of Copenhagen, 3C Blegdamsvej, DK-2200 Copenhagen N, Denmark

(Correspondence should be addressed to P Thams; Email: thams{at}imbg.ku.dk)

Objective: To assess the significance of protein kinase A (PKA) in glucose triggering of ATP-sensitive K⁺ (K⁺_ATP) channel-dependent insulin secretion and in glucose amplification of K⁺_ATP channel-independent insulin secretion.

Methods: Insulin release from cultured perifused mouse pancreatic islets was determined by radioimmunoassay.

Results: In islets cultured at 5.5 mmol/l glucose, and then perifused in physiological Krebs–Ringer medium, the PKA inhibitors, H89 (10 µmol/l) and PKI 6–22 amide (30 µmol/l) did not inhibit glucose (16.7 mmol/l)-induced insulin secretion, but inhibited stimulation by the adenylyl cyclase activator, forskolin (10 µmol/l). In the presence of 60 mmol/l K⁺ and 250 µmol/l diazoxide, which stimulates maximum Ca²⁺ influx independently of K⁺_ATP channels, H89 (10 µmol/l) inhibited Ca²⁺-evoked insulin secretion, but failed to prevent glucose amplification of K⁺_ATP channel-independent insulin secretion. In the presence of 1 mmol/l ouabain and 250 µmol/l diazoxide, which cause modest Ca²⁺ influx, glucose amplification of K⁺_ATP channel-independent insulin secretion was observed without concomitant Ca²⁺ stimulation of PKA activity. In islets cultured at 16.7 mmol/l glucose, glucose (16.7 mmol/l)-induced insulin secretion in physiological Krebs–Ringer medium was augmented and now inhibited by H89 (10 µmol/l), implicating that culture at 16.7 mmol/l glucose may increase Ca²⁺-sensitive adenylyl cyclase activity and hence PKA activity. In accordance, Ca²⁺-evoked insulin secretion at 60 mmol/l K⁺ and 250 µmol/l diazoxide was improved, whereas glucose amplification of K⁺_ATP channel-independent insulin secretion was unaffected.

Conclusions: Glucose may activate PKA through triggering of the K⁺_ATP channel-dependent pathway. Glucose amplification of K⁺_ATP channel-independent insulin secretion, on the other hand, occurs by PKA-independent mechanisms.

This article has been cited by other articles:

				N. K. Hoa, A. Norberg, R. Sillard, D. Van Phan, N. D. Thuan, D. T. N. Dzung, H. Jornvall, and C.-G. Ostenson The possible mechanisms by which phanoside stimulates insulin secretion from rat islets J. Endocrinol., February 1, 2007; 192(2): 389 - 394. [Abstract] [Full Text] [PDF]