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This Article Full Text Full Text (PDF) All Versions of this Article: 290/2/E308    most recent 00131.2005v1 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 (4) Citing Articles via Google Scholar Google Scholar Articles by Takahashi, R. Articles by Oka, Y. Search for Related Content PubMed PubMed Citation Articles by Takahashi, R. Articles by Oka, Y.

Cell type-specific activation of metabolism reveals that -cell secretion suppresses glucagon release from -cells in rat pancreatic islets

Divisions of ¹Molecular Metabolism and Diabetes and ²Advanced Therapeutics for Metabolic Diseases, Tohoku University Graduate School of Medicine, Sendai, Miyagi; and ³Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan

Submitted 22 March 2005 ; accepted in final form 19 September 2005

Abnormal glucagon secretion is often associated with diabetes mellitus. However, the mechanisms by which nutrients modulate glucagon secretion remain poorly understood. Paracrine modulation by - or -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 -cells and non--cells separately in rat islets. NaDC-1 expression only in non--cells, among which -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 -cells and non--cells. Similarly, an increase in glucagon release with glycerol was observed when GlyK was expressed only in non--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 -cells. These data demonstrate that glucagon secretion from rat -cells depends on -cell activation and provide insights into the coordinated mechanisms underlying hormone secretion from pancreatic islets.

pancreatic islet; paracrine regulation; glucagon secretion; cell activation

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				R. Takahashi, H. Ishihara, K. Takahashi, A. Tamura, S. Yamaguchi, T. Yamada, H. Katagiri, and Y. Oka Efficient and controlled gene expression in mouse pancreatic islets by arterial delivery of tetracycline-inducible adenoviral vectors J. Mol. Endocrinol., January 1, 2007; 38(1): 127 - 136. [Abstract] [Full Text] [PDF]