PMID- 16188913
OWN - NLM
STAT- MEDLINE
DCOM- 20060222
LR  - 20061115
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 290
IP  - 2
DP  - 2006 Feb
TI  - Cell type-specific activation of metabolism reveals that beta-cell secretion 
      suppresses glucagon release from alpha-cells in rat pancreatic islets.
PG  - E308-16
AB  - Abnormal glucagon secretion is often associated with diabetes mellitus. However, 
      the mechanisms by which nutrients modulate glucagon secretion remain poorly 
      understood. Paracrine modulation by beta- or delta-cells is among the postulated 
      mechanisms. Herein we present further evidence of the paracrine mechanism. First, 
      to activate cellular metabolism and thus hormone secretion in response to 
      specific secretagogues, we engineered insulinoma INS-1E cells using an 
      adenovirus-mediated expression system. Expression of the Na+-dependent 
      dicarboxylate transporter (NaDC)-1 resulted in 2.5- to 4.6-fold (P < 0.01) 
      increases in insulin secretion in response to various tricarboxylic acid cycle 
      intermediates. Similarly, expression of glycerol kinase (GlyK) increased insulin 
      secretion 3.8- or 4.2-fold (P < 0.01) in response to glycerol or 
      dihydroxyacetone, respectively. This cell engineering method was then modified, 
      using the Cre-loxP switching system, to activate beta-cells and non-beta-cells 
      separately in rat islets. NaDC-1 expression only in non-beta-cells, among which 
      alpha-cells are predominant, caused an increase (by 1.8-fold, P < 0.05) in 
      glucagon secretion in response to malate or succinate. However, the increase in 
      glucagon release was prevented when NaDC-1 was expressed in whole islets, i.e., 
      both beta-cells and non-beta-cells. Similarly, an increase in glucagon release 
      with glycerol was observed when GlyK was expressed only in non-beta-cells but not 
      when it was expressed in whole islets. Furthermore, dicarboxylates suppressed 
      basal glucagon secretion by 30% (P < 0.05) when NaDC-1 was expressed only in 
      beta-cells. These data demonstrate that glucagon secretion from rat alpha-cells 
      depends on beta-cell activation and provide insights into the coordinated 
      mechanisms underlying hormone secretion from pancreatic islets.
FAU - Takahashi, Rui
AU  - Takahashi R
AD  - Div. of Molecular Metabolism and Diabetes, Tohoku Univ. Graduate School of 
      Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
FAU - Ishihara, Hisamitsu
AU  - Ishihara H
FAU - Tamura, Akira
AU  - Tamura A
FAU - Yamaguchi, Suguru
AU  - Yamaguchi S
FAU - Yamada, Takahiro
AU  - Yamada T
FAU - Takei, Daisuke
AU  - Takei D
FAU - Katagiri, Hideki
AU  - Katagiri H
FAU - Endou, Hitoshi
AU  - Endou H
FAU - Oka, Yoshitomo
AU  - Oka Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050927
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Dicarboxylic Acid Transporters)
RN  - 0 (Organic Anion Transporters, Sodium-Dependent)
RN  - 0 (Recombinant Proteins)
RN  - 0 (SLC13A2 protein, human)
RN  - 0 (Symporters)
RN  - 9007-92-5 (Glucagon)
RN  - EC 2.7.1.30 (Glycerol Kinase)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Dicarboxylic Acid Transporters/genetics/metabolism
MH  - Glucagon/*metabolism
MH  - Glucagon-Secreting Cells/*metabolism
MH  - Glycerol Kinase/genetics/metabolism
MH  - Insulin-Secreting Cells/*metabolism
MH  - Organic Anion Transporters, Sodium-Dependent/genetics/metabolism
MH  - Paracrine Communication/*physiology
MH  - Rats
MH  - Recombinant Proteins/metabolism
MH  - Symporters/genetics/metabolism
EDAT- 2005/09/29 09:00
MHDA- 2006/02/24 09:00
CRDT- 2005/09/29 09:00
PHST- 2005/09/29 09:00 [pubmed]
PHST- 2006/02/24 09:00 [medline]
PHST- 2005/09/29 09:00 [entrez]
AID - 00131.2005 [pii]
AID - 10.1152/ajpendo.00131.2005 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2006 Feb;290(2):E308-16. doi: 
      10.1152/ajpendo.00131.2005. Epub 2005 Sep 27.