Insulin stimulates cationic amino acid transport activity in the isolated perfused rat pancreas

Abstract

SUMMARYThe effects of exogenous insulin, glucagon and streptozotocin-diabetes on influx (15 s) of L-lysine via a cationic amino acid transporter resembling system y+ were investigated in the isolated perfused rat pancreas. In non-diabetic pancreata, transport of L-lysine was saturable with an apparent Km of 2-11 + 0.29 mm and Vma_ of 2 21 + 0 20,mol min-' g-1 (n = 6). Bovine insulin (100 # u ml ') increased the maximal transport rate (Vmax = 349 + 030 /tmol min-' g-', n = 4, P < 0.05) for L-lysine 1 6-fold without altering the Km. L-Lysine transport was not elevated significantly in diabetic pancreata, although insulin (1O00 /tu ml-') enhanced transport to values measured in non-diabetic preparations. Human glucagon (1.5 x 10-9 M) had no stimulatory effect on L-lysine transport. These findings provide the first evidence that exogenous insulin stimulates cationic amino acid transport activity in the exocrine pancreatic epithelium. Activation of the cationic pancreatic amino acid transporter may provide a mechanism to enhance the supply of L-arginine and thus sustain nitric oxide-mediated pancreatic secretion in response to islet hormones and secretagogues.

Cell signalling-mediating insulin increase of mRNA expression for cationic amino acid transporters-1 and -2 and membrane hyperpolarization in human umbilical vein endothelial cells

“…Our results show that L-arginine transport occurs with relatively high affinity (K m 85 µM), is Na + -independent and inhibited by membrane depolarization, supporting previous reports showing that L-arginine transport in these cells is mediated primarily by the high-affinity membrane transporters hCAT-1 (K m ≈100-200 µM) or hCAT-2B (K m ≈200-400 µM) [3,10,39,45,50]. Insulin increases L-arginine transport in HUVEC [39,45] and activates Na + -independent L-lysine transport in rat pan- [29] and L-arginine transport in gastric mucosa [6]. Our results show that the insulin-mediated increase in Larginine transport was associated with a higher V max with no changes in the apparent K m .…”

“…Insulin increases the activity of system y + /CATs in HUVEC [45], rat pancreas [29], gastric mucosa [6] and CAT-1 expression in rat liver cells [49] and coronary myocytes [43]. However, there are no reports on the cell signalling mechanisms involved in the modulation of L-arginine transport and hCAT-1 and hCAT-2B expression in response to insulin in human endothelium [26,46].…”

l-Arginine Uptake in Normal and Diabetic Rat Retina and Retinal Pigment Epithelium

“…On the contrary, arginine uptake by normal rat RPE increased considerably due to the presence of insulin, high glucose concentrations or of insulin in combination with high glucose concentrations in the incubation medium. Although the mechanism of this increase is not understood, insulin is known to regulate a variety of amino acid transporters [28][29][30][31], and therefore glucose could indirectly raise the capacity of the arginine transporter.…”

Elevated D‐glucose induces insulin insensitivity in human umbilical endothelial cells isolated from gestational diabetic pregnancies

“…Insulin also enhances system y¤ activity in gastric glands (Contreras et al 1997), pancreas (Muñoz, Sweiry & Mann, 1995) and liver cells (Wu, Robinson, Kung & Hatzoglou, 1994). Other studies in umbilical vein endothelial cells have shown that both IGF_1 and insulin stimulate NO production via a Ca¥-independent mechanism (Tsukahara, Gordienko, Tonshoff, Gelato & Goligorsky, 1994).…”