Mechanism of β-adrenergic agonist-induced transmural transport of glucose in rat small intestine

Abstract

The perfusion of rat small intestine with 10 microM epinephrine (Epi) or 10 microM norepinephrine resulted in significant increases in the amount of 3-O-[methyl-3H]-D-glucose transported from the mucosal to serosal side. The Epi-induced increases in glucose transport were coupled with selective increases in beta-adrenoceptor density in the mucosal membranes. Treatment with 0.1 microM okadaic acid increased glucose transport even in the absence of Epi, but that with 1 microM staurosporine or 60 microM N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide dihydrochloride completely inhibited the increases in glucose transport induced by 10 microM Epi or 10 microM dibutyryl cAMP. The maximal binding sites (Bmax) of [3H]phlorizin in brush border membrane (BBM) from tissues perfused with Epi was increased, showing increases in the binding ability of the Na+/glucose cotransporter (SGLT1) to glucose. Phosphorylation and dephosphorylation of BBM with protein kinase A (PKA) and alkaline phosphatase resulted in increases and decreases in Bmax of [3H]phlorizin, respectively. The phosphorylation state of SGLT1 immunoprecipitated from BBM incubated with [gamma-32P]ATP-Mg2+ and PKA, and the analysis of phosphoamino acids composed of SGLT1 in rats given [32P]orthophosphate indicate the presence of potential sites for PKA-mediated phosphorylation of SGLT1 at serine. These findings indicate that the regulation of phosphorylation of SGLT1 leads to an alteration of its function and results in the control of glucose transport in the rat small intestine.

Tripeptides of RS1 (RSC1A1) Inhibit a Monosaccharide-dependent Exocytotic Pathway of Na+-d-Glucose Cotransporter SGLT1 with High Affinity

“…It is regulated in response to diet and during food intake via changes of expression, location, and activity of SGLT1 and/or GLUT2 (2,10,11,12). Expression of SGLT1 is influenced by ␤-adrenergic innervation (13), glucagon-like peptide 2 (14), and cholecystokinin (15). Cyclic AMP, protein kinase A, protein kinase C (PKC), 3 and phosphoinositol 3-kinase are involved in the regulatory pathways (13,14,16).…”

The Plasma Membrane-associated Protein RS1 Decreases Transcription of the Transporter SGLT1 in Confluent LLC-PK1 Cells

“…Regulation of SGLT1 has been studied in small intestine (7,(11)(12)(13), in Xenopus oocytes (14), and in the renal epithelial cell line LLC-PK 1 which is derived from porcine kidney proximal tubule cells (15)(16)(17)(18)(19)(20)(21)(22). One of the factors that affect the expression of SGLT1 in small intestine and LLC-PK 1 cells is extracellular D-glucose concentration (7,17,18).…”

Impaired intestinal and renal glucose transport in PDK-1 hypomorphic mice

“…Irrespective of the underlying mechanism, the observations disclose that SGLT-1 activity in the brush-border membrane is regulated by PDK-1. The ␤-adrenergic regulation of glucose transport in rat small intestine has previously been shown to involve phosphorylation-dependent SGLT-1 stimulation (19), whereas IGF-mediated stimulation of intestinal glucose transport via SGLT-1 has been reported to involve increase of mRNA and protein abundance (25).…”