Diabetes, Vol 47, Issue 9 1426-1435, Copyright © 1998 by American Diabetes Association

ARTICLES

Role of cAMP in upregulation of insulin secretion during the adaptation of islets of Langerhans to pregnancy

AJ Weinhaus, NV Bhagroo, TC Brelje and RL Sorenson
Department of Cell Biology and Neuroanatomy, University of Minnesota Medical School, Minneapolis 55455-0303, USA.

Islets undergo a number of upregulatory changes to meet the increased demand for insulin during pregnancy, including an increase in glucose-stimulated insulin secretion with a reduction in the stimulation threshold. Treatment with the lactogenic hormone prolactin (PRL) in vitro has been shown to induce changes in islets similar to those observed during pregnancy. We examined cAMP production in islets treated with PRL to determine if changes in cAMP are involved in the upregulation of insulin secretion. Insulin secretion and cAMP concentrations were measured from islets in response to a suprathreshold (6.8 mmol/l) or high (16.8 mmol/l) glucose concentration in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine. Insulin secretion increased by 2.1-, 5.0-, and 5.9-fold at the suprathreshold glucose concentration and by 1.6-, 2.3-, and 2.9-fold at the higher glucose concentration after 1, 3, and 5 days of PRL treatment, respectively. After a similar pattern, cAMP metabolism increased by 1.2-, 1.6-, and 2.1-fold at the suprathreshold glucose concentration and by 1.2-, 1.7-, and 2.2-fold at the high glucose concentration after 1, 3, and 5 days of PRL treatment, respectively. The similar increases in insulin secretion and cAMP concentration suggest that changes in cAMP metabolism are involved in lactogen-induced upregulation of insulin secretion. To gain additional insight into the role of cAMP in the upregulation of islet function after lactogen treatment, we examined the relationship between changes in cAMP concentration and insulin secretion. Under all conditions (differing glucose concentrations and time periods), the increase in insulin release was directly proportional to the increase in cAMP. Thus increased glucose-stimulated insulin secretion from lactogen-treated islets could be accounted for by increased generation of cAMP and did not appear to require any further specific changes in intracellular processes mediated by cAMP. Because the PRL receptor is not directly involved in cAMP metabolism, the lactogen-induced increase in cAMP was most likely due to the increase in glucose metabolism that we have previously demonstrated in PRL-treated islets and in islets during pregnancy.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. J Weinhaus, L. E Stout, N. V Bhagroo, T C. Brelje, and R. L Sorenson Regulation of glucokinase in pancreatic islets by prolactin: a mechanism for increasing glucose-stimulated insulin secretion during pregnancy J. Endocrinol., June 1, 2007; 193(3): 367 - 381. [Abstract] [Full Text] [PDF]

				M. J. Holness, G. K. Greenwood, N. D. Smith, and M. C. Sugden Peroxisome Proliferator-Activated Receptor-{alpha} and Glucocorticoids Interactively Regulate Insulin Secretion During Pregnancy Diabetes, December 1, 2006; 55(12): 3501 - 3508. [Abstract] [Full Text] [PDF]

				M. Milanski, V. C. Arantes, F. Ferreira, M. A. d. B. Reis, E. M. Carneiro, A. C. Boschero, C. B. Collares-Buzato, and M. Q. Latorraca Low-Protein Diets Reduce PKA{alpha} Expression in Islets from Pregnant Rats J. Nutr., August 1, 2005; 135(8): 1873 - 1878. [Abstract] [Full Text] [PDF]

				J. Shao, L. Qiao, and J. E. Friedman Prolactin, progesterone, and dexamethasone coordinately and adversely regulate glucokinase and cAMP/PDE cascades in MIN6 {beta}-cells Am J Physiol Endocrinol Metab, February 1, 2004; 286(2): E304 - E310. [Abstract] [Full Text] [PDF]

				M. Tsutsumi, T. H. Claus, Y. Liang, Y. Li, L. Yang, J. Zhu, F. Dela Cruz, X. Peng, H. Chen, S. L. Yung, et al. A Potent and Highly Selective VPAC2 Agonist Enhances Glucose-Induced Insulin Release and Glucose Disposal: A Potential Therapy for Type 2 Diabetes Diabetes, May 1, 2002; 51(5): 1453 - 1460. [Abstract] [Full Text] [PDF]

				M. J. Holness and M. C. Sugden Dexamethasone during Late Gestation Exacerbates Peripheral Insulin Resistance and Selectively Targets Glucose-Sensitive Functions in {beta} Cell and Liver Endocrinology, September 1, 2001; 142(9): 3742 - 3748. [Abstract] [Full Text] [PDF]

				Y. Q. Liu, P. W. Nevin, and J. L. Leahy beta -Cell adaptation in 60% pancreatectomy rats that preserves normoinsulinemia and normoglycemia Am J Physiol Endocrinol Metab, July 1, 2000; 279(1): E68 - E73. [Abstract] [Full Text] [PDF]

				Z. Ma, S. Ramanadham, M. Wohltmann, A. Bohrer, F.-F. Hsu, and J. Turk Studies of Insulin Secretory Responses and of Arachidonic Acid Incorporation into Phospholipids of Stably Transfected Insulinoma Cells That Overexpress Group VIA Phospholipase A2 (iPLA2beta ) Indicate a Signaling Rather Than a Housekeeping Role for iPLA2beta J. Biol. Chem., April 13, 2001; 276(16): 13198 - 13208. [Abstract] [Full Text] [PDF]