Excitatory GABAergic action and increased vasopressin synthesis in hypothalamic magnocellular neurosecretory cells underlie the high plasma level of vasopressin in diabetic rats

Young Beom Kim, Woong Bin Kim, Won Woo Jung, Xiangyan Jin, Yoon Sik Kim, Byoungjae Kim, Hee Chul Han, Gene D. Block, Christopher S. Colwell, Yang In Kim

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Diabetes mellitus (DM) is associated with increased plasma levels of arginine-vasopressin (AVP), which may aggravate hyperglycemia and nephropathy. However, themechanisms by which DM may cause the increased AVP levels are not known. Electrophysiological recordings in supraoptic nucleus (SON) slices from streptozotocin (STZ)-induced DM rats and vehicle-treated control rats revealed that γ-aminobutyric acid (GABA) functions generally as an excitatory neurotransmitter in the AVP neurons of STZ rats, whereas it usually evokes inhibitory responses in the cells of control animals. Furthermore,Western blotting analyses of Cl- transporters in the SON tissues indicated that Na+-K+-2CΓ- cotransporter isotype 1 (a Cl- importer) was upregulated and K+-Cl- cotransporter isotype 2 (KCC2; a Cl- extruder) was downregulated in STZ rats. Treatment with CLP290 (a KCC2 activator) significantly lowered blood AVP and glucose levels in STZ rats. Last, investigation that used rats expressing an AVP-enhanced green fluorescent protein fusion gene showed that AVP synthesis in AVP neurons was much more intense in STZ rats than in control rats. We conclude that altered Cl- homeostasis that makes GABA excitatory and enhanced AVP synthesis are important changes in AVP neurons thatwould increase AVP secretion in DM. Our data suggest that Cl- transporters in AVP neurons are potential targets of antidiabetes treatments.

Original languageEnglish
Pages (from-to)486-495
Number of pages10
JournalDiabetes
Volume67
Issue number3
DOIs
Publication statusPublished - 2018 Mar 1

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Arginine Vasopressin
Vasopressins
Streptozocin
Diabetes Mellitus
Neurons
Supraoptic Nucleus
gamma-Aminobutyric Acid
Aminobutyrates
Experimental Diabetes Mellitus
Gene Fusion
Hyperglycemia
Neurotransmitter Agents
Homeostasis
Down-Regulation
Western Blotting
Glucose

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Excitatory GABAergic action and increased vasopressin synthesis in hypothalamic magnocellular neurosecretory cells underlie the high plasma level of vasopressin in diabetic rats. / Kim, Young Beom; Kim, Woong Bin; Jung, Won Woo; Jin, Xiangyan; Kim, Yoon Sik; Kim, Byoungjae; Han, Hee Chul; Block, Gene D.; Colwell, Christopher S.; Kim, Yang In.

In: Diabetes, Vol. 67, No. 3, 01.03.2018, p. 486-495.

Research output: Contribution to journalArticle

Kim, Young Beom ; Kim, Woong Bin ; Jung, Won Woo ; Jin, Xiangyan ; Kim, Yoon Sik ; Kim, Byoungjae ; Han, Hee Chul ; Block, Gene D. ; Colwell, Christopher S. ; Kim, Yang In. / Excitatory GABAergic action and increased vasopressin synthesis in hypothalamic magnocellular neurosecretory cells underlie the high plasma level of vasopressin in diabetic rats. In: Diabetes. 2018 ; Vol. 67, No. 3. pp. 486-495.
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abstract = "Diabetes mellitus (DM) is associated with increased plasma levels of arginine-vasopressin (AVP), which may aggravate hyperglycemia and nephropathy. However, themechanisms by which DM may cause the increased AVP levels are not known. Electrophysiological recordings in supraoptic nucleus (SON) slices from streptozotocin (STZ)-induced DM rats and vehicle-treated control rats revealed that γ-aminobutyric acid (GABA) functions generally as an excitatory neurotransmitter in the AVP neurons of STZ rats, whereas it usually evokes inhibitory responses in the cells of control animals. Furthermore,Western blotting analyses of Cl- transporters in the SON tissues indicated that Na+-K+-2CΓ- cotransporter isotype 1 (a Cl- importer) was upregulated and K+-Cl- cotransporter isotype 2 (KCC2; a Cl- extruder) was downregulated in STZ rats. Treatment with CLP290 (a KCC2 activator) significantly lowered blood AVP and glucose levels in STZ rats. Last, investigation that used rats expressing an AVP-enhanced green fluorescent protein fusion gene showed that AVP synthesis in AVP neurons was much more intense in STZ rats than in control rats. We conclude that altered Cl- homeostasis that makes GABA excitatory and enhanced AVP synthesis are important changes in AVP neurons thatwould increase AVP secretion in DM. Our data suggest that Cl- transporters in AVP neurons are potential targets of antidiabetes treatments.",
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