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

American Journal of Physiology. Endocrinology and Metabolism
Lin Li, Burton M Wice

Abstract

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 b...Continue Reading

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Citations

Apr 28, 2010·The Journal of Biological Chemistry·Burton M WiceKenneth S Polonsky
Apr 2, 2011·PloS One·Barry R BochnerBridget K Wagner
Jul 7, 2009·Neuropharmacology·Maria P YavropoulouJohn G Yovos
Mar 29, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Wendell J LuPatrick Tso
Aug 18, 2016·American Journal of Physiology. Endocrinology and Metabolism·Paul B HigginsFranco Folli
Jul 18, 2015·American Journal of Physiology. Gastrointestinal and Liver Physiology·Joseph F PierreMichelle E Kimple

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