Kelly, Lisa and Almutairi, Mohammed M. and Kursan, Shams and Pacheco, Romario and Dias-Junior, Eduardo and Castrop, Hayo and Di Fulvio, Mauricio (2019) Impaired glucose tolerance, glucagon, and insulin responses in mice lacking the loop diuretic-sensitive Nkcc2a transporter. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 317 (4). C843-C856. ISSN 0363-6143, 1522-1563
Full text not available from this repository. (Request a copy)Abstract
The Na+ K+ 2Cl(-) cotransporter-2 (Nkcc2. Slc12a1) is abundantly expressed in the kidney and its inhibition with the loop-diuretics bumetanide and furosemide has been linked to transient or permanent hyperglycemia in mice and humans. Notably, Slc12a1 is expressed at low levels in hypothalamic neurons and in insulin-secreting beta-cells of the endocrine pancreas. The present study was designed to determine if global elimination of one of the Slc12a1 products, i.e., Nkcc2 variant a (Nkcc2a). the main splice version of Nkcc2 found in insulin-secreting beta-cells, has an impact on the insulin and glucagon secretory responses and fuel homeostasis in vivo. We have used dynamic tests of glucose homeostasis in wild-type mice and mice lacking both alleles of Nkcc2a (Nkcc2a(KO)) and assessed their islet secretory responses in vitro. Under basal conditions. Nkcc2a(KO) mice have impaired glucose homeostasis characterized by increased blood glucose. intolerance to the sugar. delayed/blunted in vivo insulin and glucagon responses to glucose, and increased glycemic responses to the gluconeogenic substrate alanine. Further, we provide evidence of conserved quantitative secretory responses of Nkcc2a(KO) islets within a context of increased islet size related to hyperplastic/hypertrophic glucagon- and insulin-positive cells (alpha-cells and beta-cells. respectively), normal total islet Cl- content, and reduced beta-cell expression of the Cl- extruder Kcc2.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NA-K-2CL COTRANSPORTER; FUNCTIONAL-CHARACTERIZATION; MOLECULAR CHARACTERIZATION; SMALL-INTESTINE; MOUSE MODEL; BETA-CELLS; GLUCONEOGENESIS; VASOPRESSIN; RELEASE; METABOLISM; glucagon; glucose homeostasis; insulin; Slc12a1/Nkcc2a; Slc12a5/Kcc2 |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Wolf Hayo Castrop |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Mar 2020 07:22 |
| Last Modified: | 26 Mar 2020 07:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26111 |
Actions (login required)
 |
View Item |
