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 language | English |
|---|---|
| Pages (from-to) | 486-495 |
| Number of pages | 10 |
| Journal | Diabetes |
| Volume | 67 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2018 Mar 1 |
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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 journal › Article
}
TY - JOUR
T1 - Excitatory GABAergic action and increased vasopressin synthesis in hypothalamic magnocellular neurosecretory cells underlie the high plasma level of vasopressin in diabetic rats
AU - Kim, Young Beom
AU - Kim, Woong Bin
AU - Jung, Won Woo
AU - Jin, Xiangyan
AU - Kim, Yoon Sik
AU - Kim, Byoungjae
AU - Han, Hee Chul
AU - Block, Gene D.
AU - Colwell, Christopher S.
AU - Kim, Yang In
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85042617360&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042617360&partnerID=8YFLogxK
U2 - 10.2337/db17-1042
DO - 10.2337/db17-1042
M3 - Article
C2 - 29212780
AN - SCOPUS:85042617360
VL - 67
SP - 486
EP - 495
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 3
ER -