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) All Versions of this Article: 288/1/E208    most recent 00346.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in 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 Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Li, L. Articles by Wice, B. M. Search for Related Content PubMed PubMed Citation Articles by Li, L. Articles by Wice, B. M.

Bombesin and nutrients independently and additively regulate hormone release from GIP/Ins cells

Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, Saint Louis, Missouri

Submitted 30 July 2004 ; accepted in final form 17 September 2004

Glucose-dependent insulinotropic polypeptide (GIP) regulates glucose homeostasis and high-fat diet-induced obesity and insulin resistance. Therefore, elucidating the mechanisms that regulate GIP release is important. GIP is produced by K cells, a specific subtype of small intestinal enteroendocrine (EE) cell. Bombesin-like peptides produced by enteric neurons and luminal nutrients stimulate GIP release in vivo. We previously showed that PMA, bombesin, meat hydrolysate, glyceraldehyde, and methylpyruvate increase hormone release from a GIP-producing EE cell line (GIP/Ins cells). Here we demonstrate that bombesin and nutrients additively stimulate hormone release from GIP/Ins cells. In various cell systems, bombesin and PMA regulate cell physiology by activating PKD signaling in a PKC-dependent fashion, whereas nutrients regulate cell physiology by inhibiting AMPK signaling. Western blot analyses of GIP/Ins cells using antibodies specific for activated and/or phosphorylated forms of PKD and AMPK and one substrate for each kinase revealed that bombesin and PMA, but not nutrients, activated PKC, but not PKD. Conversely, nutrients, but not bombesin or PMA, inhibited AMPK activity. Pharmacological studies showed that PKC inhibition blocked bombesin- and PMA-stimulated hormone release, but AMPK activation failed to suppress nutrient-stimulated hormone secretion. Forced expression of constitutively active vs. dominant negative PKDs or AMPKs failed to perturb bombesin- or nutrient-stimulated hormone release. Thus, in GIP/Ins cells, PKC regulates bombesin-stimulated hormone release, whereas nutrients may control hormone release by regulating the activity of AMPK-related kinases, rather than AMPK itself. These results strongly suggest that K cells in vivo independently respond to neuronal vs. nutritional stimuli via two distinct signaling pathways.

K cells; protein kinase C; protein kinase D; adenosine 5'-monophosphate-activated protein kinase; adenosine 5'-monophosphate-activated protein kinase-related kinase; enteric neurons; nutrient sensing

This article has been cited by other articles:

				M. C. Althage, E. L. Ford, S. Wang, P. Tso, K. S. Polonsky, and B. M. Wice Targeted Ablation of Glucose-dependent Insulinotropic Polypeptide-producing Cells in Transgenic Mice Reduces Obesity and Insulin Resistance Induced by a High Fat Diet J. Biol. Chem., June 27, 2008; 283(26): 18365 - 18376. [Abstract] [Full Text] [PDF]

				W. J. Lu, Q. Yang, W. Sun, S. C. Woods, D. D'Alessio, and P. Tso Using the lymph fistula rat model to study the potentiation of GIP secretion by the ingestion of fat and glucose Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1130 - G1138. [Abstract] [Full Text] [PDF]